: DIAGNOSIS AND TREATMENT

Jassin M. Jouria, MD

Dr. Jassin M. Jouria is a medical doctor, professor of academic medicine, and medical author. He graduated from Ross University School of Medicine and has completed his clinical clerkship training in various teaching hospitals throughout New York, including King’s County Hospital Center and Brookdale Medical Center, among others. Dr. Jouria has passed all USMLE medical board exams, and has served as a test prep tutor and instructor for Kaplan. He has developed several medical courses and curricula for a variety of educational institutions. Dr. Jouria has also served on multiple levels in the academic field including faculty member and Department Chair. Dr. Jouria continues to serves as a Subject Matter Expert for several continuing education organizations covering multiple basic medical sciences. He has also developed several continuing medical education courses covering various topics in clinical medicine. Recently, Dr. Jouria has been contracted by the University of Miami/Jackson Memorial Hospital’s Department of Surgery to develop an e-module training series for trauma patient management. Dr. Jouria is currently authoring an academic textbook on Human Anatomy & Physiology.

ABSTRACT

The diagnosis and treatment of has undergone much progress in terms of new preventive and medical therapies in addition to surgical approaches based on prostate cancer type and staging. While some lifestyle patterns have been studied to prevent prostate cancer, more research is needed to determine how lifestyle factors are associated with a reduction in the incidence of prostate cancer. Challenges and complications in the diagnosis and treatment of prostate cancer that health providers and nurses face while caring for patients are discussed.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1 Continuing Nursing Education Course Director & Planners

William A. Cook, PhD, Director, Douglas Lawrence, MA, Webmaster,

Susan DePasquale, MSN, FPMHNP-BC, Lead Nurse Planner

Policy Statement

This activity has been planned and implemented in accordance with the policies of NurseCe4Less.com and the continuing nursing education requirements of the American Nurses Credentialing Center's Commission on Accreditation for registered nurses. It is the policy of NurseCe4Less.com to ensure objectivity, transparency, and best practice in clinical education for all continuing nursing education (CNE) activities.

Continuing Education Credit Designation

This educational activity is credited for 5 hours. Nurses may only claim credit commensurate with the credit awarded for completion of this course activity.

Pharmacology content is 1 hour.

Statement of Learning Need

Prostate cancer is one of the most prevalent forms of cancer among men, second only to . Health professionals need to be knowledgeable about the symptoms, stages, and various treatments to ensure the best possible outcome of care for patients with prostate cancer.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 2 Course Purpose

To provide nurses and associates with knowledge of prevention, cause and treatment of prostate cancer.

Target Audience

Advanced Practice Registered Nurses and Registered Nurses

(Interdisciplinary Health Team Members, including Vocational Nurses and Medical Assistants may obtain a Certificate of Completion)

Course Author & Director Disclosures

Jassin M. Jouria, MD, William S. Cook, PhD, Douglas Lawrence, MA

Susan DePasquale, MSN, FPMHNP-BC – all have no disclosures

Acknowledgement of Commercial Support

There is no commercial support for this course.

Activity Review Information

Reviewed by Susan DePasquale, MSN, FPMHNP-BC

Start Date: 4/26/2016 Termination Date: 4/26/2019

Please take time to complete a self-assessment of knowledge, on page 4, sample questions before reading the article.

Opportunity to complete a self-assessment of knowledge learned will be provided at the end of the course.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 3 1. Prostate cancer typically develops in the ______zone of the prostate.

a. transition b. central c. anterior d. peripheral

2. The ______is primarily comprised of muscle tissue.

a. anterior zone b. vas deferens c. central zone d. seminal vesicles

3. Lack of vegetables in the diet (especially broccoli-family vegetables) is linked to

a. slow-growing tumors. b. low-risk prostate cancer. c. higher risk of aggressive prostate cancer. d. genetic factors related to prostate cancer.

4. True or False: Body mass index, a measure of obesity, IS linked to being diagnosed with prostate cancer.

a. True b. False

5. In most instances, when physicians discuss prostate cancer, they’re referring to

a. urothelial cell . b. bladder cancer. c. . d. adenocarcinoma.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 4 Introduction

Prostate cancer is one of the most prevalent forms of cancer among men, second only to skin cancer. It has a very high success rate in treatment and recovery due in part to its typical slow-growth pattern. However, it is important to remember that not all forms of prostate cancer are slow growing and that not all prostate cancer patients are cured. As a result, health professionals need to be aware of the symptoms, stages, and various treatments to ensure the best possible outcome for their patients. This course will provide a general overview of current concepts, diagnostic advances, and novel therapeutic approaches to the management of prostate cancer.

The Prostate

The prostate is a conglomeration of tiny glands, ducts, and muscle tissue encased by fibrous tissue. It produces fluid that contains hormones and proteins to keep sperm alive after ejaculation as the sperm searches for an egg to fertilize. The average size of a prostate is about 30 to 40 grams, about the size of a small lime or walnut. Its texture is firm. About one-third of the prostate is composed of muscular tissue, with the rest being glandular tissue. As a man ages, his prostate often gets bigger, sometimes doubling or tripling in size. Although there is a lot of discussion about prostate enlargement in aging men and the uncomfortable symptoms that this can cause, it is important to remember that not all men experience prostate enlargement, and cancer is not responsible for this enlargement.

The prostate’s zones include the transition, the central, the anterior, and the peripheral.1

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 5  Transition Zone:

The transition zone is the most interior part of the prostate; it immediately surrounds the urethra (the slender tube that carries urine away from the bladder and out of the body through the tip of the penis). The transition zone can begin to grow after age 40, with this noncancerous enlargement possibly leading to urinary difficulties.

 Central Zone:

The central zone is located near the bladder and is the seat of about one third of the glands that make and secrete prostatic fluid. The central zone, similar to the transition zone, is generally the part of the prostate that grows after a man turns age 40. Prostate cancer is unusual in the central zone and if it does develop, it tends to be a slower growing type of cancer.

 Anterior Zone:

The anterior zone is primarily comprised of muscle tissue.

 Peripheral Zone:

The peripheral zone is located at the back of the gland and is the portion closest to the . It contains most of the secretion- producing glands and is where prostate cancer typically develops.

Medical providers typically describe a right side and a left side when referring to the prostate, but in reality there is only a subtle demarcation between the two sides. Think of a plum. It is one fruit but the small groove down the middle leaves the impression of two halves. That’s similar to the prostate gland.2

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 6 A measurement of the location of the prostate within the pelvic area will show that it is approximately two inches from the perineum, which is the region of exterior skin and internal muscle between the anus and the scrotum. The gland sits just below the bladder and in front of the rectum. Off the base of the prostate and behind the bladder are the two seminal vesicles, which produce most of the fluid that makes up the ejaculate. The base of the prostate is the wider part of the gland that nestles up to the bladder. The apex is the more pointed end of the gland that faces down toward the perineum. Just before ejaculation, sperm from the testicles is transported into the urethra by a long tube called the vas deferens. This sperm combines with fluid both from the seminal vesicles and the prostate, creating semen. The prostate and adjacent muscular contractions then propel the semen out of the urethra through the tip of the penis for ejaculation.3

Prostate Cancer Incidence And Statistics

The diagnosis of prostate cancer rapidly increased in the mid-1980s, with the advent of the serological biomarker prostate specific antigen (PSA) test (discussed below), which has played a pivotal role in the screening and early detection of prostate cancer worldwide. The current lifetime risk of developing prostate cancer is 17%, with an estimated lifetime cancer specific mortality risk of 3%. Prostate cancer is the most commonly diagnosed non– skin cancer in men in the U.S., with a lifetime risk for diagnosis currently estimated at 15.9%. Most cases of prostate cancer have a good prognosis even without treatment, but some cases are aggressive; the lifetime risk for dying of prostate cancer is 2.8%. Over two million men in the U.S. count themselves as prostate cancer survivors, and this number continues to grow.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 7 Risk Factors Of Prostate Cancer

There are several major factors that influence risk, and some of them unfortunately cannot be changed.4

 Age:

Prostate cancer is rare before age 50 years, and very few men die of prostate cancer before age 60 years. Seventy percent of deaths due to prostate cancer occur after age 75 years. Thus, the older the patient, the more likely he is to be diagnosed with prostate cancer. For example, only 1 in 10,000 men under age 40 will be diagnosed with prostate cancer; the rate shoots up to 1 in 38 for ages 40 to 59; and 1 in 14 for ages 60 to 69. In fact, more than 65% of all prostate are diagnosed in men over the age of 65. The average age at diagnosis of prostate cancer in the U.S. is 69 years. After that age, the chance of developing prostate cancer becomes more common than any other cancer in men or women.

 Race:

African American men are more likely to develop prostate cancer compared with Caucasian men and are nearly 2.5 times as likely to die from the disease. Conversely, Asian men who live in Asia have the lowest risk.

 Family history/genetics:

A man with a father or brother who developed prostate cancer is twice as likely to develop the disease. This risk is further increased if the cancer was diagnosed in family members at a younger age (less than 55 years of age) or if it affected three or more family members.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 8  Location of residence:

For men in the U.S., the risk of developing prostate cancer is 17%. For men who live in rural China, it’s 2%. However, when Chinese men move to the western culture, their risk increases substantially. Men who live in cities north of 40 degrees latitude (north of Philadelphia, Pennsylvania, Columbus, Ohio, and Provo, Utah, for instance) have the highest risk for dying from prostate cancer of any men in the U.S. This effect appears to be mediated by inadequate sunlight during three months of the year, which reduces vitamin D levels.

Aggressive versus Slow-Growing Cancers

In the past few years, health providers have realized that prostate cancer is actually linked to several diseases with different causes. More aggressive and fatal cancers likely have different underlying causes than slow-growing tumors. For example, while smoking has not been thought to be a risk factor for low-risk prostate cancer, it may be a risk factor for aggressive prostate cancer. Likewise, lack of vegetables in the diet (especially broccoli-family vegetables) is linked to a higher risk of aggressive prostate cancer, but not to low-risk prostate cancer.5

Body mass index, a measure of obesity, is not linked to being diagnosed with prostate cancer overall. In fact, obese men may have relatively lower PSA levels than non-obese men due to dilution of the PSA in a larger blood volume. However, obese men are more likely to have aggressive disease.6 Other risk factors for aggressive prostate cancer include:  Tall height  Lack of exercise and a sedentary lifestyle  High calcium intake  African-American race nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 9  Family history  Agent Orange exposure

Research in the past few years has shown that diet modification may decrease the chances of developing prostate cancer, reduce the likelihood of having a prostate cancer recurrence, or help slow the progression of the disease.

Prostate Conditions and Other Related Risks

The most common misconception is that the presence of non-cancerous conditions of the prostate will increase the risk of prostate cancer. While these conditions can cause symptoms similar to those of prostate cancer and should be evaluated by a physician, there is no evidence to suggest that having the following conditions will increase a man’s risk for developing prostate cancer.7

Benign Prostatic and Prostatitis

Benign Prostatic Hyperplasia (BPH) is a non-cancerous enlargement of the prostate. Because the urethra (the tube that carries urine from the bladder out of the body) runs directly through the prostate, enlargement of the prostate in BPH squeezes the urethra, making it difficult and often painful for men to urinate.

Prostatitis, an infection in the prostate, is the most common cause of urinary tract infections in men. Most treatment strategies are designed to relieve the symptoms of prostatitis, which include fever, chills, burning during urination, or difficulty urinating. There have been links between inflammation of the prostate and prostate cancer in several studies. This may be a result of

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 10 being screened for cancer just by having prostate related symptoms, and currently this is an area of controversy.

Sexual Activity

High levels of sexual activity or frequent ejaculation have been rumored to increase prostate cancer risk. This is untrue. In fact, studies show that men who report more frequent ejaculations may have a lower risk of developing prostate cancer.

Vasectomy

Having a vasectomy was originally thought to increase a man’s risk, but this has since been disproven.

Medications

Several recent studies have shown a link between aspirin intake and a reduced risk of prostate cancer by 10-15%. This may result from different screening practices, through a reduction of inflammation, or other unknown factors. The class of drugs called the statins - known to lower cholesterol - has also recently been linked to a reduced risk of aggressive prostate cancer in some studies.

Alcohol

There is no link between alcohol and prostate cancer risk.

Vitamin E

Recent studies have not shown a benefit to the consumption of vitamin E or selenium (in the formulations studied) in the prevention of prostate cancer.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 11 Overview of Prostate Cancer

Prostate cancer is an uncontrolled growth of cells that line the ducts of the prostate gland. These abnormal cells can spread throughout the prostate and nearby organs, such as the seminal vesicles. If not caught early, they can spread (metastasize) to other regions of the body through the lymph or blood systems.8

In most instances, when health providers discuss prostate cancer, they are referring to adenocarcinoma. This cancer arises from the cells of the prostate’s ducts. However, there are a few other rare cancers in the prostate. One is urothelial cell carcinoma (UCC). Urothelial cell carcinoma originates from the layer of cells that line the inside of the urethra and the bladder. This tumor is frequently seen in association with bladder cancer.9

An extremely rare cancer of the prostate is a sarcoma. A sarcoma originates from the muscular and connective tissue in the prostate and is treated quite differently. Compared to most other kinds of cancer, prostate adenocarcinoma is usually very slow growing. It can begin at a relatively early age, possibly when a man is in his 30s or 40s. Because it grows so slowly, it is not usually diagnosed until after age 55 to 60. In some situations, though, the cancer will grow and spread very fast. There are several ways to predict the tumor’s speed of growth. The first is to watch how fast the PSA level is rising; this is called PSA velocity. Another measure is the Gleason score. A higher Gleason score indicates a more aggressive cancer. A final method involves repeated physical examination or studies (such as an MRI or bone scans) to monitor growth of the cancer.10,11

Prostate cancer can spread in several ways. It usually spreads first through the capsule of the prostate. This spread outside the gland is often only a few

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 12 millimeters. It can also move into the seminal vesicles. Spread to the seminal vesicles is seen less often these days, probably because the disease is being caught earlier.12

Prostate cancer can occasionally spread to other parts of the body. Cancer cells can enter the lymphatic vessels around the prostate and then spread to the lymph nodes in the pelvis. Another way prostate cancer spreads is through the bloodstream. Ultimately, cancer cells that enter the lymph channels can spread (through the blood) to almost any organ in the body. Because of what seem to be special growth factors, the prostate cancer cells have an affinity for growing in bone — often the bones of the spine, pelvis, or long bones, such as the femur (upper leg) or humerus (upper arm).13 To determine if prostate cancer has spread to the bone, a bone scan is performed in some prostate cancer patients. If prostate cancer cells begin to grow in the bones, it is still considered prostate cancer (not bone cancer) and may be treated with hormonal and radiation therapies.14

Symptoms of Prostate Cancer

Many times, prostate cancer will produce no recognizable symptoms in patients. However, many men will not recognize when they are experiencing symptoms because they are similar to many other conditions. For individuals who do notice the presence of symptoms, the following are the most common that they experience.27

Local Symptoms:  Urinary frequency  Urinary urgency  Decreased stream  Hematuria

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 13 Metastatic Symptoms:

 Weight loss  Loss of appetite  Bone pain  Lower extremity pain  Edema  Uremic symptoms

Diagnosing Prostate Cancer

Typically, screening will be conducted in order of least to most invasive. However, if there is significant concern that the cancer may already have reached an advanced stage, more aggressive screening procedures may be used without conducting initial diagnostic procedures. The provider will determine which screening procedures to order depending in each individual patient’s needs and situation.28

All contemporary recommendations for prostate cancer screening incorporate the measurement of serum PSA levels; other methods of detection, such as digital rectal examination or ultrasonography, may be included. Prostate cancer screening will find prostate cancer in one in every eight men during their lifetime. Prostate cancer represents 25% of all new cases of male cancers. Screening is designed to detect early stage, asymptomatic prostate cancer, as the patient's chances of cure are higher when the cancer is diagnosed at an early stage.15 Before specific screening procedures are discussed, it is important to be aware of the concern that prostate cancer may be over-diagnosed and over-treated.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 14 Over-diagnosis and Over-treatment

Although the PSA test lowers mortality rates for prostate cancer, there is still concern that over-diagnosis may lead to over-treatment of cancers that would not progress enough to significantly affect a patient’s health for several years:16 for example, there is convincing evidence that PSA-based screening programs result in the detection of many cases of asymptomatic prostate cancer. A substantial percentage of men who have asymptomatic cancer detected by PSA screening have a tumor that either will not progress or will progress so slowly that it would have remained asymptomatic for the man's lifetime. The terms “over-diagnosis” or “pseudo-disease” are used to describe both situations.

The rate of over-diagnosis of prostate cancer increases as the number of men subjected to increases. The number of cancer cases that could be detected in a screened population is large. A single study in which men eligible for PSA screening had a biopsy regardless of PSA level detected cancer in nearly 25% of men. The rate of over-diagnosis also depends on life expectancy at the time of diagnosis. A cancer diagnosis in men with shorter life expectancies because of chronic diseases or age is much more likely to lead to over-diagnosis. The precise magnitude of over diagnosis associated with any screening and treatment program is difficult to determine, but estimates from the 2 largest trials suggest over-diagnosis rates of 17% to 50% for prostate cancer screening.9,16-19

Benefits of Detection and Early Treatment

The primary goal of prostate cancer screening is to reduce deaths due to prostate cancer and, thus, increase length of life. An additional important outcome would be a reduction in the development of symptomatic metastatic disease. Reduction in prostate cancer mortality was the primary nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 15 outcome used in available randomized, controlled trials of prostate cancer screening. Although one screening trial reported on the presence of metastatic disease at the time of prostate cancer diagnosis, no study reported on the effect of screening on the development of subsequent metastatic disease, making it difficult to assess the effect of lead-time bias on the reported rates.20

Men with screen-detected cancer can potentially fall into 1 of 3 categories: those whose cancer will result in death despite early diagnosis and treatment, those who will have good outcomes in the absence of screening, and those for whom early diagnosis and treatment improve survival. Only randomized trials of screening allow an accurate estimate of the number of men who fall into the last category. There is convincing evidence that the number of men who avoid dying from prostate cancer because of screening after 10 to 14 years is, at best, very small.

The U.S. Preventive Services Task Force (USPSTF) considered two major trials of PSA screening, which were the U.S. PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial and the ERSPC (European Randomized Study of Screening for Prostate Cancer). The U.S. trial did not demonstrate any reduction of prostate cancer mortality. The European trial found a reduction in prostate cancer deaths of approximately 1 death per 1000 men screened in a subgroup aged 55 to 69 years. This result was heavily influenced by the results of 2 countries; 5 of the 7 countries reporting results did not find a statistically significant reduction. All-cause mortality in the European trial was nearly identical in the screened and nonscreened groups. There is adequate evidence that the benefit of PSA screening and early treatment ranges from 0 to 1 prostate cancer deaths avoided per 1000 men screened.13,21-25

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 16 Harms Related to Screening and Diagnostic Procedures

Convincing evidence demonstrates that the PSA test often produces false- positive results: approximately 80% of positive PSA test results are false- positive when cutoffs between 2.5 and 4.0 µg/L are used (4.0 ng/ml is the total PSA value below which prostate cancer is considered unlikely). There is adequate evidence that false-positive PSA test results are associated with negative psychological effects, including persistent worry about prostate cancer. Men who have a false-positive test result are more likely to have additional testing, including 1 or more , in the following year than those who have a negative test result.

Over 10 years, approximately 15% to 20% of men will have a PSA test result that triggers a biopsy, depending on the PSA threshold and testing interval used. New evidence from a randomized trial of treatment of screen- detected cancer indicates that roughly one third of men who have experience pain, fever, bleeding, infection, transient urinary difficulties, or other issues requiring clinician follow-up that the men consider a “moderate or major problem”; approximately 1% require hospitalization.16,17,26

Screening For Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement.15

The USPSTF considered the magnitude of these harms associated with screening and diagnostic procedures to be at least small.

Although the precise, long-term effect of PSA screening on prostate cancer–specific mortality remains uncertain, existing studies adequately demonstrate that the reduction in prostate cancer mortality after 10 to 14 years is, at most, very small, even for men in what seems to be the optimal age range of 55 to 69 years. There is no apparent reduction in all-cause mortality.

In contrast, the harms associated with the diagnosis and treatment of screen-detected cancer are common, occur early, often persist, and include a small but real risk for premature death. Many more men in a screened population will experience the harms of screening and treatment of screen-detected disease than will experience the benefit. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 17 The inevitability of overdiagnosis and overtreatment of prostate cancer as a result of screening means that many men will experience the adverse effects of diagnosis and treatment of a disease that would have remained asymptomatic throughout their lives. Assessing the balance of benefits and harms requires weighing a moderate to high probability of early and persistent harm from treatment against the very low probability of preventing a death from prostate cancer in the long term.

The USPSTF concludes that there is moderate certainty that the benefits of PSA-based screening for prostate cancer do not outweigh the harms.

Implementation Although the USPSTF discourages the use of screening tests for which the benefits do not outweigh the harms in the target population, it recognizes the common use of PSA screening in practice today and understands that some men will continue to request screening and some physicians will continue to offer it. The decision to initiate or continue PSA screening should reflect an explicit understanding of the possible benefits and harms and respect the patients' preferences.

Physicians should not offer or order PSA screening unless they are prepared to engage in shared decision-making that enables an informed choice by the patients. Similarly, patients requesting PSA screening should be provided with the opportunity to make informed choices to be screened that reflect their values about specific benefits and harms. Community- and employer-based screening should be discontinued.

The treatment of some cases of clinically localized prostate cancer can change the natural history of the disease and may reduce morbidity and mortality in a small percentage of men, although the prognosis for clinically localized cancer is generally good regardless of the method of detection, even in the absence of treatment. The primary goal of PSA-based screening is to find men for whom treatment would reduce morbidity and mortality. Studies demonstrate that the number of men who experience this benefit is, at most, very small, and PSA-based screening as currently implemented in the United States produces more harms than benefits in the screened population.

It is not known whether an alternative approach to screening and management of screen-detected disease could achieve the same or greater benefits while reducing the harms. Focusing screening on men at increased risk for prostate cancer mortality may improve the balance of benefits and harms, but existing studies do not allow conclusions about a greater absolute or relative benefit from screening in these populations.

Lengthening the interval between screening tests may reduce harms without affecting cancer mortality; the only screening trial that demonstrated a prostate cancer–specific mortality benefit generally used a 2- to 4-year screening interval. Other potential ways to reduce diagnostic- and treatment-related harms include increasing the PSA threshold used to trigger the decision for biopsy or need for treatment, or reducing the number of men having active treatment at the time of diagnosis through watchful waiting or active surveillance.

Periodic digital rectal examinations could also be an alternative strategy worthy of further study. In the only randomized trial demonstrating a mortality reduction from radical prostatectomy for clinically localized cancer, a high percentage of men had palpable cancer.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 18 All of these approaches require additional research to better elucidate their merits and pitfalls and more clearly define an approach to the diagnosis and management of prostate cancer that optimizes the benefits while minimizing the harms.

Patient Population Under Consideration This recommendation applies to men in the general U.S. population. Older age is the strongest risk factor for the development of prostate cancer. However, neither screening nor treatment trials show benefit in men older than 70 years.

Across age ranges, black men and men with a family history of prostate cancer have an increased risk of developing and dying of prostate cancer. Black men are approximately twice as likely to die of prostate cancer than other men in the United States and the reason for this disparity is unknown. Black men represented a small minority of participants in the randomized clinical trials of screening (4% of enrolled men in the PLCO trial were non-Hispanic black; although the ERSPC and other trials did not report the specific racial demographic characteristics of participants, they probably were predominately white). Thus, no firm conclusions can be made about the balance of benefits and harms of PSA-based screening in this population. However, it is problematic to selectively recommend PSA-based screening for black men in the absence of data that support a more favorable balance of risks and benefits.

A higher incidence of cancer will result in more diagnoses and treatments, but the increase may not be accompanied by a larger absolute reduction in mortality. Preliminary results from PIVOT (Prostate Cancer Intervention Versus Observation Trial), in which 30% of enrollees were black, have become available since the publication of the USPSTF's commissioned evidence reviews. Investigators found no difference in outcomes due to treatment of prostate cancer in black men compared with white men.

Exposure to Agent Orange (a defoliant used in the Vietnam War) is considered to be a risk factor for prostate cancer, although few data exist on the outcomes or effect of PSA testing and treatment in these persons. The Veterans Health Administration considers prostate cancer in Vietnam veterans who were exposed to Agent Orange a service- connected condition.

The USPSTF did not evaluate the use of the PSA test as part of a diagnostic strategy in men with symptoms potentially suggestive of prostate cancer. However, the presence of urinary symptoms was not an inclusion or exclusion criterion in screening or treatment trials, and approximately one quarter of men in screening trials had bothersome lower urinary tract symptoms (nocturia, urgency, frequency, and poor stream). The presence of benign prostatic hyperplasia is not an established risk factor for prostate cancer, and the risk for prostate cancer among men with elevated PSA levels is lower in men with urinary symptoms than in men without symptoms. This recommendation also does not include the use of the PSA test for surveillance after diagnosis or treatment of prostate cancer and does not consider PSA-based testing in men with known BRCA gene mutations who may be at increased risk for prostate cancer.

Screening Tests Prostate-specific antigen–based screening in men aged 50 to 74 years has been evaluated in 5 unique randomized, controlled trials of single or interval PSA testing with various PSA cutoffs and screening intervals, along with other screening methods, such as digital rectal examination or transrectal ultrasonography.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 19 Screening tests or programs that do not incorporate PSA testing, including digital rectal examination alone, have not been adequately evaluated in controlled studies. The PLCO trial found a nonstatistically significant increase in prostate cancer mortality in the annual screening group at 11.5 and 13 years, with results consistently favoring the usual care group.

A prespecified subgroup analysis of men aged 55 to 69 years in the ERSPC trial demonstrated a prostate cancer mortality rate ratio (RR) of 0.80 (95% CI, 0.65 to 0.98) in screened men after a median follow-up of 9 years, with similar findings at 11 years (RR, 0.79 [CI, 0.68 to 0.91]). Of the 7 centers included in the ERSPC analysis, only 2 countries (Sweden and the Netherlands) reported statistically significant reductions in prostate cancer mortality after 11 years (5 did not), and these results seem to drive the overall benefit found in this trial. No study reported any factors, including patient age, adherence to site or study protocol, length of follow-up, PSA thresholds, or intervals between tests, that could clearly explain why mortality reductions were larger in Sweden or the Netherlands than in other European countries or the United States (PLCO trial). Combining the results through meta-analysis may be inappropriate due to clinical and methodological differences across trials.

No study found a difference in overall or all-cause mortality. This probably reflects the high rates of competing mortality in this age group, because these men are more likely to die of prostate cancer, as well as the limited power of prostate cancer screening trials to detect differences in all-cause mortality, should they exist. Even in the “core” age group of 55 to 69 years in the ERSPC trial, only 462 of 17 256 deaths were due to prostate cancer. The all-cause mortality RR was 1.00 (CI, 0.98 to 1.02) in all men randomly assigned to screening versus no screening. Results were similar in men aged 55 to 69 years. The absence of any trend toward a reduction in all-cause mortality is particularly important in the context of the difficulty of attributing death to a specific cause in this age group.

Diagnostic Procedures To Determine Prostate Cancer

There are a number of diagnostic procedures that can be used to determine the presence of prostate cancer.

Digital Rectal Exam

During a digital rectal exam (DRE), the health provider inserts a gloved finger inside the rectum to examine the part of the prostate that’s closest to the rectal wall. The provider is searching for any areas that feel abnormal, or have an unusual firmness or a lump (). Such an abnormality may

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 20 indicate the presence of prostate cancer. Simply because the health provider feels an irregularity doesn’t mean it’s prostate cancer.29

In most prostate cancer cases diagnosed today, the DRE does not reveal a nodule the doctor can feel (palpate). This is either because the cancer is small and well hidden within the normal tissue or it’s located in a portion of the gland that’s inaccessible from the rectal area. It’s the PSA blood test that usually finds these early, nonpalpable tumors.30

Prostate Specific Antigen

The use of the prostate-specific antigen (PSA) test for prostate cancer screening (since the 1990s) has led to increased early diagnoses. Prostate specific antigen is an enzyme produced by the prostate. Semen coagulates after ejaculation, and the PSA enzyme helps turn the congealed semen back into liquid so sperm can swim freely and fertilization may take place. It’s normal for small amounts of PSA to “leak” into a man’s bloodstream. The PSA blood test measures nanograms (one thousand-millionth of a gram) of PSA per milliliter of serum (the liquid part of blood), and it’s written as ng/mL.31

Noncancerous conditions, such as benign prostatic hyperplasia (BPH), prostate inflammation, prostate infection, or trauma, can elevate PSA because these conditions may cause more of the enzyme to seep into the bloodstream. An elevated PSA does not necessarily indicate cancer. It only points to something that needs further investigation.32

Although a large number of men undergo annual screening, PSA testing has never been scientifically proven to reduce the risk of dying from prostate cancer. Because false positives can lead to unnecessary biopsies - and a

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 21 biopsy is an invasive procedure - not everyone in the medical establishment universally recommends this screening procedure.33

The National Cancer Institute started the multi-institutional Prostate, Lung, Colorectal, Ovarian (PLCO) cancer screening trial in 1993 to explore whether screening for a number of cancers, including prostate, is valuable. Early findings of the PLCO trial suggest that if the PSA level is less than 1.0 ng/mL, then the patient could reduce testing to once every five years. If this PSA test is lower than 2.0 ng/mL, then the health provider might suggest getting the PSA re-tested every other year. And anyone with a PSA level above 2.0 ng/mL should continue to get a yearly PSA test. Although these are the standard recommendations, the provider will make screening recommendations based on the individual’s personal medical history.34

The PSA readings will vary depending on a number of factors. The following is a list of the different types of PSA readings one must consider when screening.

Normal PSA Reading

The upper limit of a “normal” PSA initially was thought to be 4.0 ng/mL. This level comes from screening studies that contained groups of men of various ages. The goal was to choose a PSA level that would be as sensitive as possible to cancer but not so low that many men with minimally increased PSA from benign causes would be unnecessarily biopsied.

The most recent information has suggested that it may be reasonable to consider lowering the normal PSA level to 2.5 or 3.0 ng/mL, particularly for younger men. The reason for this is that while the likelihood of a positive biopsy in the 4.0 – 10.0 ng/mL range is about 25 percent, the likelihood of a

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 22 positive biopsy in the 2.5 – 4.0 ng/mL range drops only a bit, to 15 percent to 20 percent. For some men, this one in five risk may be sufficiently high to consider a biopsy if the PSA falls in this range.

Age Adjusted PSA

Prostate specific antigen levels tend to increase as a man ages and his prostate volume increases. What may be a normal amount of PSA for a man at age 50 will be different by the time he reaches 70. For instance, if a man is younger than 50 and has a PSA of 4.5 ng/mL, his doctor might call for a biopsy. But if a 75-year-old’s PSA is 4.5 ng/mL, his doctor might consider this normal for his age and not request additional tests.

It is important to remember that age adjusted PSA levels are controversial and not everyone in the medical community agrees about their accuracy or usefulness. It has been suggested that while age adjusted PSA levels may pick up more cancers in the younger age group by using lower “normal” PSA levels, more cancer may be missed in older patients.

Age Range Worrisome PSA Level 40 – 50 >2.5 ng/mL 50 – 60 >3.0 ng/mL 60 – 70 >3.5 ng/mL 70 + >4.0 ng/mL

Free PSA

Most PSA binds to other proteins in the blood. Because this PSA is complexed or bonded to these proteins, it’s often called “complexed PSA.” The remaining unattached PSA is termed “free PSA.” Because the type of nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 23 PSA varies with different kinds of prostate tissue, men with a lower percentage of free PSA have a higher risk for prostate cancer. For example, a man whose total PSA is 8.0 ng/mL with 8 percent free PSA has a greater chance of having prostate cancer than his next door neighbor whose total PSA also is 8.0 ng/mL but with 35 percent free PSA.

A free PSA test may be requested if the PSA is between 4.0 and 10.0 ng/mL. If the test shows a low level of free PSA (usually less than 15 percent to 20 percent), biopsy is often the next step. If that biopsy turns out negative, it’s common for the health provider to ask the patient to come back for another biopsy in six months or a year. This is because a low level of free PSA means something may be going on that bears watching. However, a man who is found to have a high percentage of free PSA is not guaranteed to be without prostate cancer. In some cases, a biopsy of a nodule may turn up prostate cancer despite a low overall total PSA and a high level of free PSA.31

PSA Density

Larger tend to produce more PSA simply because there’s more glandular tissue to create that enzyme. This means that more PSA is available to escape into the blood. If the patient has a large prostate, an elevated PSA level may arouse less suspicion of prostate cancer. The problem with this reasoning is that a cancer can easily be overlooked in men with larger prostates. In short, most studies have shown that the PSA itself is more predictive of prostate cancer than PSA density. For this reason, PSA density is not used in deciding whether to do a biopsy.35

Prostate specific antigen density of the transition zone is a mathematical calculation. Two pieces of information are needed to arrive at this number. First is the PSA level, expressed in ng/mL. Second is the size of the central

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 24 portion of prostate measured in cubic centimeters; this measurement is achieved by using an ultrasound probe. The PSA value is divided by the measured volume. While some institutions have suggested that an upper limit of 0.15 correlates to a higher incidence of cancer and may signal the need for biopsy, very few institutions in the U.S. use it because it is a complex and expensive test.36

PSA Velocity

Prostate specific antigen velocity is the rate at which PSA rises over time. If the PSA rise is less than 0.75 ng/mL in a given year, it is typically not worrisome. However, a PSA level that rises faster than that hints at something unusual. If a PSA has climbed more than 0.75 ng/mL in less than a year regardless of the absolute level of PSA, the health provider may call for further testing.37

Factors Affecting PSA Levels

Ejaculation can increase the PSA level in the some men. The increase, however, is usually minimal and the PSA usually returns to normal within 48 hours. If a man wants to minimize the risk of his PSA being elevated, he should avoid ejaculation for a few days before the PSA test.

Infection of the prostate can cause inflammation and elevate the PSA level. The usual symptoms of a prostate infection are increased urinary frequency and discomfort in the pelvis. Prostate infections are sometimes hard to diagnose.38 While a urinalysis is the best test to evaluate an infection of the bladder, it may not detect infection of the prostate. In other words, a negative urinalysis does not mean the prostate is not infected. A second step is often a massage of the prostate to express fluid, which is then examined microscopically for signs of infection. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 25 If the health provider still suspects an infection in the prostate, an antibiotic may be prescribed. The medication will kill the offending bacteria, and the PSA level should decrease in several weeks to months. If the PSA does not decrease, a biopsy may be recommended.

Amount and Frequency of PSA Testing

It is important to find out if something other than cancer is causing the PSA increase. If infection or inflammation is not causing the PSA rise, a biopsy is the usual next step. If this biopsy is negative and the PSA remains elevated, a repeat biopsy may be recommended, often taking a larger number of biopsy samples. If the repeat biopsy is again negative, the patient will usually undergo repeat PSA tests at 6- to 12-month intervals. The health provider may recommend subsequent biopsies based on changes in PSA, changes in the digital rectal exam, or the provider’s level of concern.36

Prostatic Acid Phosphatase

An older test, prostatic acid phosphatase (PAP), measures another enzyme produced by the prostate. Although some men with prostate cancer have increased amounts of prostatic acid phosphatase, this test is not nearly as good at picking up early prostate cancer as the PSA test. That’s why PAP is rarely used anymore as a screening method. It is true that a high PAP level can signal locally advanced or metastatic disease in men who have already been diagnosed with prostate cancer. But other factors, such as a PSA level and the Gleason score (explained later), are generally better predictors of the cancer’s extent than PAP.39

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 26 Tissue Tests

The vast majority of patients with early stage prostate cancer do not have symptoms, which is why getting both regular PSA tests and DREs is important. If the PSA level and the DRE are both normal, there’s little need for additional testing because the chance of a positive biopsy under these conditions is very low. That being said, up to 25 percent of prostate cancers do not cause a PSA elevation. These may be high-grade (meaning faster- growing) tumors that have lost the ability to produce PSA like their normal prostate cell counterparts. That’s why there’s no increase in PSA. A nodule or firmness may be the only way to detect these types of tumors. This is just one more example of why DREs and PSA tests are used together. In these instances, tissue testing is typically required to determine if cancer is present.31

A biopsy simply means removing and microscopically examining several pieces of tissue from the prostate. Most medical providers use an ultrasound guided technique for prostate biopsies, which involves inserting an ultrasound probe into the rectum to view the prostate. This may be slightly uncomfortable but it’s usually not painful.40

Using a guide that’s attached to the probe, the provider directs the needle to a specific area and then triggers the rapid, automated biopsy unit. The needle removes a very small core of tissue in a split second. Separate needle sticks remove 6 to 12 samples (called core biopsies) in rapid succession. Many providers today use local anesthesia around the prostate to minimize pain from a biopsy. The entire biopsy process lasts only a few minutes and most men experience few side effects. Common minor side effects are a small amount of bleeding from the rectum or urine and blood in the semen.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 27 It’s important to recognize that small amounts of blood in the semen can persist for several weeks.41

To reduce the risk of bleeding, it is usually recommended that patients avoid aspirin, anticoagulants such as warfarin, and nonsteroidal anti-inflammatory medications such as ibuprofen for a week prior to the biopsy. The provider might also prescribe antibiotics to reduce the chance of infection following the biopsy.42

There is no “best” number of biopsy cores, but initial studies a number of years ago considered sextant biopsies (six cores) standard. Sextant biopsies remove samples from the base, mid-gland, and apex on both left and right lobes of the prostate. Many studies now show that increasing the number of cores from six to ten or twelve will identify more men with significant prostate cancer. These additional samples usually come from the outside edges of the gland. If it is suspected that the cancer is in the front (anterior) or central part of the gland, one or two samples may be taken from this area, too. Taking these additional cores has the advantage of reducing the risk of missing important cancer. Plus, these additional cores may reduce the need for a repeat biopsy if this first biopsy turns out to be negative.43

In about 75 percent of men with an elevated PSA, the biopsy will be negative. For some of these men, however, a number of circumstances may lead to the recommendation of a repeat biopsy. The risk factors may include (1) a worrisome DRE, (2) a clearly elevated PSA, (3) a rising PSA, (4) a strong family history of prostate cancer, and (5) precancerous changes found in the first biopsy. When the biopsy should be repeated is a matter of some debate. Certainly the greater the concern about prostate cancer risk,

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 28 the sooner the repeat biopsy can be done. This is where the advice and counsel of the health provider is important.28

Prostate cancer has particular, well-known features that distinguish it from the normal prostate cells that form small glands within the prostate. The pathologist is looking for changes in the shape and size of these cells and glands. The pathologist will examine the pattern of the cancer cells and assign a number from one to five to the most common pattern seen. A grade of 1 denotes cancerous cells that are most like normal cells (these cells are known as well-differentiated cells), and a grade of 5 is assigned to cells that are the most malignant. The pathologist then identifies the second most common pattern and again assigns a grade of 1 to 5. The two grades are added together to create the Gleason score.

All Gleason scores range from 2 to 10. Most prostate cancers diagnosed today have Gleason scores of 5, 6, or 7. The more aggressive prostate cancers are 8, 9, and 10. Gleason grade 2, 3, or 4 prostate cancer is uncommon these days and almost never seen on a needle biopsy. Lower Gleason scores indicate more slow-growing tumors that are more likely to be contained within the prostate gland (localized) for a longer time. These tumors may not even require treatment in older men. Higher Gleason scores behave just the opposite. They tend to spread rapidly and aggressive treatment is often recommended.44,45

The Report

A pathology report includes crucial information such as 1) the number of cores and where they were taken (the right base, for instance), 2) the type of cancer (such as adenocarcinoma), 3) the Gleason grade and score, 4) if there’s evidence of perineural , and, 5) how much cancer was found

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 29 in each core (5 percent, for example). All of this can help to predict the chance that the cancer is still contained in the prostate.46

Nerve branches originate in the pelvis and some of those branches enter the prostate capsule, while others course along the outside of the gland and down to the penis. Those nerves that penetrate the prostate may provide a means for the cancer cells to escape and travel beyond the prostate. Peri- is a prefix that means “near, around, or enclosing.” So, perineural invasion means the pathologist has detected cancer spreading along nerves within the prostate.2 The medical community disagrees on whether perineural invasion on a biopsy report can be reliable enough to predict cancer escape from the prostate. In 38 to 50 percent of needle biopsies in which a pathologist reports perineural invasion, at the time of surgery cancer is found to have spread beyond the capsule. However, when entire prostates with prostate cancer are examined following surgical removal, almost all of them have some perineural invasion. That’s why the finding of perineural invasion carries less weight in predicting the extent of the disease than stage, grade, and PSA.41

The acronym PIN stands for prostatic intraepithelial neoplasia; intraepithelial means “within the epithelium” or the cells that line the glandular ducts of the prostate. In this case, the normal cells that line the prostate ducts have been replaced by cells that have many features of a . While these individual cells look like cancer cells, PIN is not cancer because these cells have not invaded the prostate. Some pathologists think that PIN may be a precursor of prostate cancer. The evidence suggesting that PIN may be the forerunner of cancer includes the fact that the PIN cells have a number of cancer features, as mentioned above, and PIN is commonly found adjacent to areas of cancer.47

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 30 Atypia is the scientific shorthand for “atypical hyperplasia.” Hyperplasia is an overgrowth of normal cells. Atypical hyperplasia is an overgrowth of cells that are somewhat abnormal but do not have the characteristics of cancer. The implications of “atypia” are not well understood and are a matter of some debate. It is not clear at this time if atypia predisposes an individual to a higher risk of cancer. If the pathologist finds atypia, most health providers currently do not recommend another biopsy but may recommend a second pathologist review the sample, just to be sure.48

When it comes to PIN, the answer is usually the opposite. In many men with PIN, a repeat biopsy has a 30 percent to 60 percent chance of finding cancer, which is why most providers will recommend another biopsy. How long to wait before repeating the biopsy is a decision that will be made between the patient and his physician. While waiting a month or two can allow the inflammation from the first biopsy to subside, a pathologist would have no problem interpreting biopsy results if the patient went ahead with another biopsy right away. Many patients prefer a second biopsy quickly to reduce the anxiety of not knowing.49

Pelvic Lymph Node Dissection

A pelvic lymph node dissection is the surgical removal of some groups of lymph nodes in the pelvis to find out if the prostate cancer has spread. Lymph node dissection is most often done during a radical prostatectomy (total surgical removal of the prostate). In some instances, though, some pelvic lymph nodes are removed for examination even if the patient does not have a prostatectomy. This is done by a means of a laparoscope — a slender tube inserted into the abdomen through a tiny incision — or a separate open operation.50

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 31 Biopsy Errors and Follow-Up Recommendations

Four general conditions would prompt a physician to seek a second opinion on a biopsy specimen:51 1. If the pathologist is uncertain as to whether cancer is present. 2. If there is a very tiny amount of early, low-grade cancer or suspicious cells. 3. If the initial pathologist is not experienced in diagnosing and prostate cancer, or the report fails to state all of the important features of the cancer (such as biopsy site, Gleason pattern score, and amount of cancer in each needle biopsy sample). 4. If low-grade cancer is diagnosed on a needle biopsy (Gleason score 2, 3, or 4, but such scores are virtually always seen only on transurethral resection of the prostate [TURP] biopsies, not needle biopsies).

A biopsy error is extremely rare because each lab has quality assurance procedures in place to help keep this from happening. Pathologists are very careful to be sure that cancer is or is not present before they report their findings. If there is any question regarding the diagnosis, they can ask for a second opinion. Many pathologists take the extra step of having their colleagues confirm the diagnosis before issuing a report. However, a prostate cancer diagnosis can be a difficult determination and even the most experienced of prostate cancer pathologists can disagree on the diagnosis from time to time.52

Ploidy Analysis

Ploidy analysis examines the DNA content of cells. The general rule is that the more malignant a cell is, the greater the amount of DNA in the cell’s nucleus. This is due to the fact that cancer is an uncontrolled growth of cells and the DNA is the first to replicate as the abnormal cell gets ready to nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 32 divide. Since ploidy analysis can gauge an abnormal amount of DNA, it seems to be a measure of the degree of malignancy. The ploidy reading can vary from one place to another in an individual’s cancer. Most experienced physicians feel that ploidy analysis is of much less value than the grade, stage, PSA, and the number of positive biopsy cores in calculating a tumor’s aggressiveness.53

Transrectal Ultrasound

Ultrasound helps in guiding the needle into the proper position within the prostate at the time of biopsy. But ultrasound, by itself, cannot reliably detect prostate cancer and is rarely helpful in determining the cancer’s stage. While many have tried to correlate ultrasound findings with the presence of cancer, it’s now apparent that the ultrasound images don’t do an adequate job of accurately identifying prostate cancer. Cancer, especially in its earliest stages, may not be seen on ultrasound. Likewise, areas that appear abnormal are not always cancerous. Biopsy is always required to make a definitive diagnosis.54

The rectal ultrasound probe emits sound waves that travel into the prostate. The sounds bounce back (echo) to create an image. The more solid or irregular the tissue, the more dense it is. This density allows the sound waves to bounce back to the ultrasound probe. This creates an image on the screen that is hyperechoic. These areas appear white on the screen. If the tissue is less dense, the image appears black because there is less tissue to reflect the sound wave. For instance, if there’s calcium in the prostate reviewers would see an intensely white image because the calcium reflects much of the sound waves. On the other hand, cystic (water-filled) and low- density areas allow sound waves to travel through without reflection. Since no echoes come back, these areas would appear black on the screen.55

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 33 A prostate with mixed changes may have some regions that are more hypoechoic (black) and some that are more hyperechoic (white). During the early years of prostate ultrasound, it was thought the cancer was generally hypoechoic. Subsequently, it has been demonstrated that cancer can have almost any ultrasound pattern. It is for this reason that ultrasound is not used for cancer detection and screening.56

Tumors often create blood vessels around them as they grow. Color Doppler ultrasound uses a special type of analysis to find areas of increased blood vessels within the prostate. While it would seem to make sense that the areas with more blood vessels might harbor regions of prostate cancer, most studies have found color Doppler ultrasound to be unreliable in finding cancer or determining its extent.57

Bone Scan

In its later stages, prostate cancer tends to spread to bone. The cancer’s activity in bone causes some bone to be reabsorbed while new bone is being created. The best way to detect this action, called bone remodeling, is with a bone scan. Fortunately, most men diagnosed with prostate cancer today do not have spread of cancer to the bone. In fact, if the PSA is less than 20 ng/mL and if the Gleason score is 7 or less, the risk of detectable spread to the bone is less than 1 percent. That’s why a bone scan is rarely recommended under these circumstances.58

Bone scans are typically conducted in a hospital’s nuclear medicine department. A small amount of radioactive material, called a radionuclide, is injected into the bloodstream through a vein in the arm. The radionuclide is not dangerous, and the body rids itself of this substance through the urine within 24 hours. It takes a couple of hours for the radioactive substance to

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 34 circulate throughout the body after it’s injected; the scan itself takes only about an hour. The patient lies down and a flat disc (the gamma camera) is positioned over the patient to record the sites where the radionuclide accumulates. More of the radionuclide settles in the areas where bone is changing or growing rapidly.59

Cancer is not the only reason the radionuclide collects in bone. Arthritis, injuries, old fractures, and even dental work show up during bone scans. If the gamma camera detects an abnormality, the usual next step is an x-ray, CT, or MRI to better evaluate that particular area.60

CT Scan

A CT (computerized tomography) scan uses a computer to combine x-ray images to create cross-sectional or three-dimensional images of an organ. CT scans cannot reliably detect prostate cancer. Nor can they reliably predict if it has spread outside the gland. Unless the prostate cancer is quite large, a CT scan may not be able to see the tumor at all.

Enlarged pelvic lymph nodes can be visualized through a CT scan, but they can’t predict if those lymph nodes are cancerous. This is why a biopsy or surgical removal is the most reliable way to assess if the cancer has migrated to the pelvic lymph nodes.61

MRI

An endorectal MRI (magnetic resonance imaging) is another method to determine whether the cancer has spread outside the prostate capsule and/or into nearby structures. It’s similar to a CT scan except instead of using x-rays, the imaging is done using a strong magnetic field. A small probe in the rectum (endorectal) allows the MRI to create detailed images of nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 35 the prostate anatomy, urethra, and the neurovascular bundles. While initial studies suggested that endorectal MRI might be helpful, most subsequent evaluations have found it not particularly useful in determining if cancer has spread outside the prostate. This is not surprising because when spread occurs it is so small that it is often detectable only with a microscope. With PSA under 15–20 ng/mL, there is a low risk of the cancer in the lymph nodes. Imaging scans in these circumstances is almost always unfruitful and can sometimes mistakenly suggest spread of the disease when the cancer is actually confined to the gland.62,63

Magnetic Resonance Spectroscopy (MRS)

Magnetic resonance spectroscopy (MRS; also called MRSI) is a relatively new technology. As with MRI, it uses a strong magnetic field and radio waves. Along with creating detailed pictures of the anatomy, MRS noninvasively gathers information about certain cellular chemicals, the concentrations of which are different in cancerous and normal cells. Abnormal amounts of these chemicals can indicate places where the cancer is present.

Early studies have suggested that combining MRI and MRS may not only help determine the aggressiveness of cancerous tumors contained within the prostate, but may also aid in assessing if and how far cancer has spread inside and possibly outside of the gland. Knowing if the cancer has spread, even in microscopic amounts, is vital in picking the best therapy. But currently MRI/MRS is not used routinely because more studies are needed to validate its effectiveness.65

ProstaScint Scan

A ProstaScint scan images molecules relatively specific to prostate cells. In a ProstaScint scan, another substance is mixed with the radionuclide before nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 36 injection. This mixture attaches itself to prostate membrane specific antigen (PSMA), large concentrations of which can indicate either prostate cells or prostate cancer. While on occasion the test can locate groups of cancer cells outside the prostate, it is unreliable, often suggesting cancer spread when none has occurred. It is for this reason that few prostate cancer specialists rely on the ProstaScint scan.66

Cancer Grouping And Staging

Once an individual undergoes testing, the medical provider will determine the extent and scope of the cancer using a system of grouping and staging. This system will provide a more thorough analysis and assessment of the cancer and will enable the provider to make a determination regarding treatment and protocol.

Gleason Scoring System

The Gleason Scoring System is the most common grading system used for prostate cancer. The higher the Gleason score, the more aggressive the cancer is and the more likely it is to have spread outside the prostate. The Gleason score is used along with stage and PSA to determine the risk of spread outside the gland. Tumors with a Gleason score of 2 through 6 generally carry a low risk of spread. Gleason 7 has a moderate risk of spread. Gleason 8, 9, or 10 tumors have a moderately high likelihood of spread outside the gland.67

The following detailed overview of Gleason Grading explains how the system is used to grade prostate cancer:68

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 37 The Gleason grading system for prostatic carcinoma is the dominant method around the world in research and in daily practice. Dr. Donald F Gleason, a pathologist in Minnesota, and members of the Veterans Administration Cooperative Urological Research Group (VACURG), developed this technique. From 1960 to 1975 the VACURG enrolled roughly 5000 prostate cancer patients in prospective randomized clinical trials. One of the outstanding strengths of the Gleason grading system is that it was tested in this large patient population, with long-term follow-up that included use of survival as an end point.

The Gleason grading system is based entirely on the histologic pattern of arrangement of carcinoma cells in H&E-stained prostatic tissue sections. Specifically, the method is one of categorization of histologic patterns 'at relatively low magnification (times 10–40) by the extent of glandular differentiation and the pattern of growth of the tumor in the prostatic stroma'.

Nine growth patterns were consolidated into five grades and these were illustrated in a drawing by Dr. Gleason.

The five basic grade patterns are used to generate a histologic score, which can range from 2 to 10, by adding the primary grade pattern and the secondary grade pattern. The primary pattern is the one that is predominant in area, by simple visual inspection. The secondary pattern is the second most common pattern. If only one grade is in the tissue sample, that grade is multiplied by two to give the score. According to the Gleason approach of 1977, if the second grade is less than 3% of the total tumor, it is ignored, and the primary grade is again doubled to give the Gleason score. Gleason sum, Gleason grade, combined Gleason grade, and category score have been used as synonyms for Gleason score, but 'histological pattern score' was the initial 1974 designation for the sum of the two patterns and 'histologic score' has endured in usage in the writings of Gleason.

The assignment of a Gleason score, which is the addition of the two most common patterns, essentially averages the primary and secondary grades. This procedure appears to be unique in grading of human cancers, where, for other malignancies, it is the worst grade that determines patient outcome. Peculiarly, for prostatic carcinoma, when there are two different Gleason grade patterns, the cancer death rates are intermediate between the rates for patients with only the pure form of each of those two grades.

The Gleason grading system allows for two separate grade patterns in an individual tissue sample, but the histomorphological appearance of prostatic carcinoma is more heterogeneous than this. Indeed, in one study, an average of 2.7 Gleason grade patterns (range 1–5) was found in in whole prostate glands. Two additional papers reported that 14–18% of patients had more than two grades in sections of their prostatic carcinoma. In one of these reports, 3% of cases had four different Gleason patterns. The number of grades assigned depends on tumor sample size and size of the tumor in the whole gland. So, more than two grades is more often observed in TURP chips (28% of cases) compared to needle biopsies (4% of cases), and tumors greater than 1–2 cm in size tended to have more than two grades.

There are limited data on how to grade carcinomas with more than two grades. Gleason wrote that the VACURG was unable to acquire enough three-grade tumors to evaluate their behavior, and proposed an algorithm to provide a Gleason score in cases with more than two grades.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 38 Recent data on radical prostatectomy specimens indicate that a high-grade Gleason pattern 4 or 5 that is a tertiary component occupying less than 5% of the tumor influences pathological stage and progression rates. Therefore, any tertiary high-grade pattern should be mentioned in surgical pathology reports. In needle biopsies, Gleason has recommended that the two highest grades be recorded. Another recommendation for needle biopsy cases in which more than two patterns are present and the worst grade is neither the predominant nor the secondary grade, the predominant and the highest grade should be chosen to arrive at a score. More data and analyses are needed to establish a definitive approach to scoring when more than two patterns are present.

'Lumping' or 'grade compression' by combining Gleason scores in attempts to translate to other grading systems should be avoided. Such grouping often results in loss of information, with the risk of combining grades of different biologic aggressiveness into one larger category. Many different approaches to lumping of Gleason scores have been published. As compared to the nine groups of Gleason score 2–10, groupings of two, three, and four categories have been utilized. A common practice has been to translate Gleason score 2–4 carcinoma as well-differentiated, Gleason score 5–7 as moderately differentiated, and Gleason score 8–10 as poorly differentiated. Yet, Gleason score 7 carcinoma harbors an element of high-grade pattern carcinoma, and is intermediate in clinical aggressiveness between patterns 5–6 and 8–10,18, 19, 20 and should not be included in a moderately differentiated category. If lumping is necessary due to low patient numbers in a research setting, the 2–6 vs 7 vs 8–10 lump or 2–4 vs 5–6 vs 7 vs 8–10 lump seems most appropriate.

Grades 1-5

Grade is not the same as stage. The pathologist grades the prostate cancer from Gleason score 2 to 10 based on how aggressive it looks under the microscope. More aggressive cancers have a different appearance under the microscope than less aggressive malignancies. The grading system most commonly used is the Gleason Scoring System. Patients are given a score based on the appearance and behavior of the cells. Each score correlates to a specific grade. Patients will be graded in categories 1 – 5.78

The following table provides a description of each of the grading categories:69

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 39 Gleason Pattern 1 This is a rare pattern of very well-differentiated growth of closely (Grade 1) packed but separate, uniform, rounded to oval, medium-sized acini. Of the original 2911 cases of prostatic carcinoma in the VACURG series, this pattern was found in 3.5% of cases. Of critical importance, this is a nodular and circumscribed mass of glands with a rounded border of tumoral–stromal interface.

Infiltration of malignant acini into surrounding stroma, including encirclement of benign glands, or penetration between benign glands, is indicative of a higher-grade carcinoma. Also, the back- to-back glands should be separated by thin stromal rims. If tumor cells form back-to-back glands, without intervening stroma, then the Gleason pattern is high-grade 4, not pattern 1 or 2. Pattern 1 is most often admixed with pattern 2 to yield a Gleason score of 38.

A pure pattern 1 adenocarcinoma, with Gleason grade 1+1=score of 2 is rare to nonexistent. In the VACURG series, score 2 adenocarcinomas comprised less than 1% of all cases. This author has never diagnosed a pure pattern 1. Combinations of pattern 1 with intermediate-grade Gleason pattern 3 and high-grade Gleason patterns 4 and 5 are vanishingly rare. Before diagnosing a pure Gleason pattern 1 adenocarcinoma, one should exclude atypical adenomatous hyperplasia (adenosis).

Pattern 1 carcinoma is most often an incidental finding in transition zone tissue, diagnosed in TURP chips resected due to a clinical diagnosis of BPH or in radical prostatectomies performed due to detection of an associated, peripheral zone, intermediate to high- grade carcinoma. It has been argued that well-differentiated Gleason pattern 1 and 2 adenocarcinomas should not be diagnosed in peripheral zone needle biopsies, since a diagnosis of Gleason score 2–4 carcinoma in needle biopsy almost always represents undergraded intermediate-grade carcinoma.

Pattern scores are strongly correlated with tumor extent, expressed as the percent area of prostate tissue in TURP chips or radical prostatectomy specimens. So, pattern 1 in scores of 2 and 3 is usually a focal finding, involving less than 5–10% of prostatic tissue.

Gleason Pattern 2 This well-differentiated pattern forms less well-defined masses that (Grade 2) are not as circumscribed as pattern 1, with a tumor–stromal boundary that is not as rounded as pattern 1. Compared to pattern 1, the carcinomatous glands of pattern 2 display a degree of separation by stroma with an average separation distance of less than one gland diameter.

Another distinctive characteristic of pattern 2 adenocarcinoma is the increase in variability in gland size and shape. There is, however, only a limited capacity to infiltrate into stroma, as suggested by some gland separation at the periphery of the tumor mass. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 40 The original description of pattern 25 and the standardized drawing of pattern 2 indicate that focal cribriform structures might be present, but cribriform arrangements are most characteristic of intermediate- to high-grade disease. Pattern 2 is usually found admixed with pattern 3 to yield a Gleason score of 5.8 In a small percentage of cases pattern 2 is pure (such that the score is 2+2=4), or is intermingled with pattern 1.

A composite of pattern 2 with high-grade patterns 4 or 5 is extremely uncommon. Pattern 2 adenocarcinoma, like pattern 1, is often an incidental finding in transition zone carcinomas and is thereby typically seen in TURP chips. Pattern 2 as a component of Gleason score 5 can also be found fairly commonly in radical prostatectomy specimens. In needle biopsy, one should diagnose pattern 2 in a Gleason score of 3 or 4 either rarely or not at all. Pattern 2 in the score setting of 4–5 is often focal (less than 10% of tissue22) but can be extensive, involving over 20–50% of TURP chip or prostatectomy tissue.

Gleason Pattern 3 This moderately differentiated grade is the most common pattern (Grade 3) of growth of prostatic adenocarcinoma, both in the pre-PSA era and in the PSA screening era. Pattern 3 has been characterized as having three distinctive appearances, designated patterns 3A, 3B, and 3C. It has been suggested that there is increased aggressiveness of pattern 3 carcinoma proceeding from pattern 3A to 3B to 3C, but no data have been published in support of this notion. Accordingly, it is not necessary to specify pattern 3A vs 3B vs 3C. Rather, these different subpatterns within the range of pattern images serve a role in recognition of grade 3 disease.

Infiltrating, medium-sized, single glands of irregular shape and spacing and haphazard, irregular extension of glands into stroma are what characterize Gleason grade pattern 3A. There is typically appreciable stromal separation of glands, where the intervening stroma is usually greater than one gland diameter. Densely packed gland arrangements are allowable in pattern 3, but there should be attendant evidence of infiltrative growth. The shape of the glands is quite variable, with angular, elongated, and 'twisted' forms described. The angular glands can have sharp corners or points. Pattern 3 adenocarcinoma glands are generally darker than well- differentiated patterns 1 and 2, which is due in part to cytoplasmic basophilia, but cytoplasmic features should not be used in Gleason grading; it is possible to detect Gleason pattern 3 glands with cytoplasmic clearing.

Pattern 3B is essentially the same as 3A except that the glands are smaller. These glands should still have the capability of forming glandular luminal spaces. If cords or chains without glandular lumina are seen, this is indicative of high-grade Gleason pattern 4, not intermediate-grade pattern 3. Pattern 3C is comprised of expanded cylinders or ducts with masses of cribriform or papillary tumor. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 41 Consistent with the possibility that this pattern actually represents intraductal growth, the tumor masses should have smooth, rounded edges, like expanded duct profiles. The Gleason grading scheme does not, however, distinguish in situ growth and invasive carcinoma, such that it is possible that some of these 3C patterns may be ducts with basal cells present. As such, some pattern 3C cribriform proliferations then represent cribriform high-grade prostatic intraepithelial neoplasia. Another view is that these duct lumen-spanning cribriform masses are intraductal carcinoma (), but this is not currently an accepted diagnostic entity. The papillary pattern 3C carcinomas, may, in similar fashion, represent in situ spread of the ductal variant of prostatic carcinoma.

Cribriform masses can also present in high-grade Gleason pattern 4, but the edges of these masses are ragged and infiltrative, not smooth. Necrosis should not be seen in pattern 3C; if necrosis is visible, pattern 5, not pattern 3, should be diagnosed. Gleason grade pattern 3 is, in the large majority of cases, found in pure form, such that the most common Gleason score is 3+3=6. It is also fairly common to identify Gleason pattern 3 in combination with low-grade pattern 2 for a score of 5 or in conjunction with pattern 4 to yield a score of 7.

In Gleason's series, a composite with pattern 5 to give a score of 8 was more common than a mingling with 4 to produce a score of 7,8 but today Gleason score 7 is more common than 8. Overall, Gleason scores of 5–7 with embedded pattern 3 are the most common histologic grades of prostatic adenocarcinoma.

Gleason Pattern 4 This is a high-grade and poorly differentiated carcinoma growth, (Grade 4) with raggedly infiltrative masses, or chains or cords of malignant epithelial cells (Figure 7). The cellular arrangements can be fused microacinar, cribriform, or papillary. Cribriform and papillary pattern 4 carcinomas can resemble cribriform and papillary pattern 3 carcinomas in gland formations and papillary projections, but pattern 4 is recognized by the ragged edges or outlines of the invasive periphery compared to the smooth, pushing borders of pattern 3C.

Carcinoma growing in this manner, but with cleared cytoplasm, is deemed pattern 4B, and can simulate renal cell carcinoma of clear cell type (hypernephroma). Thus, this variant has been termed the hypernephroid or hypernephromatoid pattern. The nuclei in pattern 4 may be deceptively bland, with little nucleomegaly and no nucleolomegaly. In these cases, highly infiltrative small, fused glands should be a clue as to the high-grade nature of the carcinoma. Pattern 4 is most often combined with pattern 3 to yield a score of 7, which is currently one of the most commonly assigned Gleason scores.

Pure high-grade disease, where there is pure pattern 4 or mingling with pattern 5 to produce scores of 8 and 9, is less common. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 42 Gleason score 8 is more common in series, such as the VACURG series, that includes higher stage, clinically nonorgan confined prostate cancer. Pattern 4 is hardly ever found with well- differentiated patterns 1 and 2.

Gleason Pattern 5 This is the most poorly differentiated pattern of prostatic (Grade 5) carcinoma, which presents in two forms—5A and 5B. There is no need to specify 5A vs 5B; the distinction is solely for the purpose of grade 5 diagnostic recognition. Pattern 5A resembles the comedo type of intraductal carcinoma of the breast, with smooth, rounded masses, cords or cylinders of carcinoma. The necrosis is typically central, being surrounded by papillary, cribriform, or solid masses of carcinoma. The appearance can be similar to pattern 3C except for the presence of necrosis.

Proteineous secretions in prostate carcinoma should not be mistaken for the tumoral cell necrosis of comedocarcinoma, where one can visualize ghost-like outlines of dead carcinoma cells, particularly at the interface of the central necrosis and the viable epithelium. Some cases of pattern 5A actually represent comedo intraductal prostatic carcinoma or in situ spread of ductal adenocarcinoma since basal cells can be observed, but in the Gleason scheme, these designations are not used, and this pattern 5A is just termed a Gleason pattern 5 adenocarcinoma.

Pattern 5B is comprised of ragged sheets of anaplastic adenocarcinoma cells. This form is so poorly differentiated that only a few small glandular lumina or signet-ring cells may be present to indicate adenocarcinoma rather than a poorly differentiated malignant of unknown cell type. In summary, raggedly infiltrative sheet-like growth and comedo necrosis are the hallmarks of Gleason pattern 5. Single cell tumor growth is often assumed to be high-grade carcinoma, but his pattern is not formally recognized in the Gleason system. Indeed, the only time single cells are mentioned in the Gleason publications is in the original 1966 description, where single cells are discussed under patterns 2 and 3. Still, if the single cells are raggedly infiltrative or of signet-ring type, then assignment of pattern 5 seems reasonable.

Pattern 5 is most often found with pattern 3, with a resultant score of 8. Less common is pure pattern 5 or comingling with pattern 4, to yield scores of 10 and 9, respectively. Gleason scores 9 and 10 are seen associated with high clinical stage disease, with clinically detectable cancer outside the prostate, either locally or in the form of metastatic disease. In only two of 2911 cases in the Gleason/VACURG series was pattern 5 detected with patterns 1 or 2.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 43 Stages I – IV

Stage is the determination of the extent of the cancer - whether it’s confined to the prostate, if it has spread to nearby tissues, or if it has metastasized (spread by way of the lymphatic system or blood vessels) to other parts of the body. Unfortunately, it is never possible to predict or detect the spread with 100 percent accuracy.70

There are two types of staging – clinical staging and pathologic staging. Clinical staging is based on the information the doctor acquires before treatment begins. The DRE is the primary means of clinical staging. Additional tests, such as a bone scan or lymph node dissection, can influence the staging. The provider’s determination of clinical stage is essential in recommending a treatment. PSA and Gleason scoring are important in terms of prognosis and treatment selection but are not a part of staging.71

Pathologic staging refers to a pathologist’s examination of the lymph nodes and prostate gland after removal. This staging can provide more exact information about tumor extension outside of the prostate, into the seminal vesicles, or to the lymph nodes and can help in determining prognosis. After all of the tests are done, the medical team carefully reviews the information it has gathered about a particular patient’s cancer to assign it a “stage.” Staging gives medical practitioners a common language to discuss the patient’s current condition, treatment, and prognosis. The most commonly used classification system is TNM (T stands for “tumor,” N means “lymph nodes,” and M designates “”). Since the TNM system was first developed, it has undergone frequent review to ensure that the classifications are as accurate as possible. Minor changes are made from time to time, and the American Joint Committee on Cancer (AJCC) regularly publishes its updates for physicians.70,72,73

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 44 TNM Grading System

The older ABCD system of staging to gauge the severity of prostate cancer has – for the most part – been replaced by the TNM system. This grading system is thought to be more accurate, and is used around the world.

 T - describes the tumor and uses different numbers to explain how large it is.  N - stands for nodes and tells whether the cancer has spread to the lymph nodes.  M - means metastatic, and tells whether the cancer has spread throughout the body.

The TNM system combines the letters with numbers to give an even more accurate description of the cancer.74

Primary tumor (T) TX cannot be assessed T0 No evidence of primary tumor T1 Clinically inapparent tumor not palpable or visible by imaging T1a Tumor incidental histologic finding in ≤5% of tissue resected T1b Tumor incidental histologic finding in >5% of tissue resected Tumor identified by needle biopsy (because of elevated prostate specific T1c antigen [PSA] level) Tumor confined within prostate; tumors found in 1 or both lobes by needle T2 biopsy but not palpable or reliably visible by imaging T2a Tumor involves one-half of 1 lobe or less T2b Tumor involves more than one-half of 1 lobe but not both lobes T2c Tumor involves both lobes Tumor extends through the prostatic capsule; invasion into the prostatic apex, T3 or the prostatic capsule is classified not as T3 but as T2 T3a Extracapsular extension (unilateral or bilateral)

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 45 T3b Tumor invading seminal vesicle(s) Tumor fixed or invades adjacent structures other than seminal vesicles (eg, T4 bladder, levator muscles, and/or pelvic wall) Pathologic (pT)* pT2 Organ confined pT2a Unilateral, involving one-half of 1 lobe or less pT2b Unilateral, involving more than one-half of 1 lobe but not both lobes pT2c Bilateral disease pT3 Extraprostatic extension pT3a Extraprostatic extension or microscopic invasion of the bladder neck pT3b Seminal vesicle invasion pT4 Invasion of the bladder and rectum

*Positive surgical margin should be indicated by an R1 descriptor (residual microscopic disease).

Regional lymph nodes (N) Clinical NX Regional lymph nodes were not assessed N0 No regional lymph node metastasis N1 Metastasis in regional lymph node(s) Pathologic PNX Regional nodes not sampled pN0 No positive regional nodes pN1 Metastases in regional nodes(s) Distant metastasis (M)* M0 No distant metastasis M1 Distant metastasis M1a Nonregional lymph nodes(s) M1b Bone(s) M1c Other site(s) with or without bone disease

*If more than 1 site of metastasis is present, use the most advanced category (pM1c).

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 46 Histopathologic Grade

Histopathologic grade (G) GX Gleason score cannot be assessed Gleason ≤6 Well differentiated (slight ) Gleason 7 Moderately differentiated (moderate anaplasia) Gleason 8-10 Poorly differentiated or undifferentiated

Anatomic Stage/Prognostic Groups

Stage T N M PSA* Gleason T1a-c N0 M0 PSA < 10 Gleason ≤6 I T2a N0 M0 PSA < 10 Gleason ≤6 T1-T2a N0 M0 PSA X Gleason X T1a-c N0 M0 PSA < 20 Gleason 7 T1a-c N0 M0 PSA ≥10 but < 20 Gleason ≤6 IIA T2a N0 M0 PSA < 20 Gleason ≤7 T2b N0 M0 PSA < 20 Gleason ≤7 T2b N0 M0 PSA X Gleason X T2c N0 M0 Any PSA Any Gleason IIB T1-2 N0 M0 PSA ≥20 Any Gleason T1-2 N0 M0 Any PSA Gleason ≥8 III T3a-b N0 M0 Any PSA Any Gleason T4 N0 M0 Any PSA Any Gleason IV Any T N1 M0 Any PSA Any Gleason Any T Any N M1 Any PSA Any Gleason

*If PSA or Gleason is not available, grouping should be determined by T stage and/or either PSA or Gleason, as available.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 47 TNM Stage Description

Stage T1 Disease

Stage T1a disease:

Stage T1a disease is always found incidentally, usually in older men who have received a surgical procedure called a transurethral resection of the prostate (TURP) to help them urinate with greater ease because their prostate is enlarged. To qualify as stage T1a, not more than 5 percent of the tissue removed during the transurethral resection can show signs of prostate cancer, and all the cancer cells must be “well differentiated” which means that the cells have a comparatively regular form and order. Stage T1a disease is best compared to stage A1 disease in the older Jewett-Whitmore staging system.

Stage T1b disease:

Stage T1b disease is very similar to stage T1a disease. It too is always found incidentally as a result of a transurethral resection of the prostate. However, we call it stage T1b as opposed to stage T1a if more than 5 percent of the tissue removed is prostate cancer tissue or if that tissue is moderately or poorly differentiated or both. We say that cancer tissue is moderately or poorly differentiated if the cancer cells have started to become disordered and to lose their structure. Stage T1b is similar to the stage called A2 in the older Jewett-Whitmore system.

Stage T1c disease:

We call a prostate cancer stage T1c when it is found at biopsy as a consequence only of the patient having a positive result to a prostate specific antigen (PSA) test but no other clinical sign of the disease (i.e., no

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 48 abnormality felt on digital rectal examination or visible on any form of imaging test).

This stage compares precisely to the so-called stage B0 disease in the Jewett-Whitmore staging system. Because of the rapid increase in the number of patients having PSA tests since the early 1990s, stage T1c has become an extremely common stage of prostate cancer to be diagnosed.

Stage T2 Disease

Stage T2a disease:

When a medical provider says a patient has stage T2a disease, it means the provider can feel the tumor in not more than half of one side (one lobe) of the prostate when performing a physical examination with DRE. The provider calls this a “palpable” tumor. Stage 2a disease may also be identified when the provider can clearly see what appears to be a tumor in not more than one half of one lobe of the prostate as a result of some type of imaging test (i.e., an ultrasound or an MRI image). Stage T2a disease is very similar to stage B1 disease in the Jewett-Whitmore system of staging.

Stage T2b disease:

Like stage T2a disease, stage T2b disease is also something the provider can feel when he does a digital rectal examination. In this case, however, more than half of one lobe (but not both lobes) of the prostate must have palpable tumor, which the provider can feel during physical exam. Stage T2b disease may also be identified when the provider can clearly see what appears to be a tumor or tumors in both halves of one lobe of the prostate as a result of some type of imaging test (i.e., an ultrasound or an MRI image). Again,

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 49 stage T2b disease is very like stage B2 disease in the older Jewett-Whitmore system.

Stage T2c disease:

Stage T2c disease is similar to the other two stage T2 disease described above, except that in this stage the provider is able to feel palpable tumor in both sides or lobes of the prostate, the left side and the right side or see such a tumor or tumors using an imaging test.

Stage T3 disease:

The two forms of stage T3 disease require extension of prostate cancer tissue through the so-called “prostatic capsule” and out of the prostate into the immediately surrounding tissue.

Stage T3a disease:

In the case of stage T3a disease the prostate cancer tissue may have extended outside the prostate capsule on one side (unilateral) or both sides (bilateral) of the prostate. Thus stage T3a is very similar to stage C1 in the Jewett-Whitmore system.

Stage T3b disease:

Stage T3b disease is used to describe prostate cancer, which has extended into one or both of the seminal vesicles (which is roughly comparable to the older stage C2 disease). However, stage T3b is also used to define disease, which combines extracapsular extension with either unilateral or bilateral seminal vesicle involvement (which is comparable to stage C3 in the Jewett- Whitmore system). It should also be noted that an older form of the TNM

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 50 staging system included a stage known as stage T3c disease that was eliminated in more recent updates to this staging system.

Stage T4 disease:

Stage T4 is a stage of prostate cancer, which had no true equivalent in the Jewett-Whitmore system. Tumor is still localized to the pelvic region, but has definitely escaped from the prostate and seminal vesicles. Tumor is normally either fixed to or invades surrounding areas, such as the bladder neck, the external sphincter, the rectum, the levator muscles, and/or the pelvic wall.

Regional Lymph Node Staging

The regional lymph nodes are the lymph nodes within the true pelvic area. They do not include distant lymph nodes that are outside the pelvic area.

 Stage Nx disease:

If the patient’s cancer is classified as Nx, this means that we simply do not know the status of the regional lymph nodes because they have not been assessed.

 Stage N0 disease:

If the patient’s cancer is classified as N0, then the lymph nodes have been assessed and there is no sign whatsoever of any cancer in the nodes examined.

 Stage N1 disease:

Cancer classified as N1 means that there is definitely cancer in one or more regional lymph nodes.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 51 Metastatic Staging

Metastatic staging refers to the presence of prostate cancer outside the pelvic area (most commonly as distant foci of cancer known as metastases).71

 Stage Mx disease:

If the patient’s cancer is classified as Mx, this means that the patient has not received tests that would allow any assessment of the possibility of metastasis.

 Stage M0 disease:

If the patient’s cancer is classified as M0, then the patient has been assessed in one or more ways and there is no evident sign whatsoever of any cancer outside the pelvic area. Many men with stage M0 disease may still have strong evidence of invisible micrometastatic disease because their PSA is rising after (for example) surgery and . Such men would be classified as having stage D1 disease according to the Jewett-Whitmore staging system.

 Stage M1 disease:

If the patient’s cancer is classified as M1, then there is clear evidence of prostate cancer somewhere outside the pelvic area. This stage is exactly comparable to stage D2 of the Jewett-Whitmore system. Some physicians may also use the following subclassifications to denote the extent of the metastatic disease:  Stage M1a: Metastasis is evident in one or more non-regional lymph node(s).

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 52  Stage M1b: Metastasis is evident in a bone or bones (i.e., in the hip or the spine).  Stage M1c: Metastasis is evident in other site(s), such as the lung or liver, with or without the presence of bone disease.

Risk Groups

Low-, intermediate-, and high-risk groups are merely a means to classify patients with similar probable outcomes (prognosis). This grouping is usually based on the three factors of stage, grade, and PSA. Patients can have different stages, Gleason scores, and PSAs, yet still have similar prognoses. There are some differing viewpoints about the cutoffs of certain measures for the low-, intermediate-, and high-risk groups, but the important point to remember is that patients in the low-risk group have the greatest chance that their cancer will be cured. They also have a low risk of recurrence. Patients in the high-risk group have a lower chance their cancer will be cured and a higher risk of recurrence. Intermediate-risk patients are somewhere in between.75

Information about a tumor’s stage influences the risk group into which a patient is placed. The term early stage is applied to small - to medium - size tumors that have a better likelihood of being totally contained within the prostate. Locally advanced cancer is thought of as a tumor that has spread outside the prostate capsule to the immediately surrounding area or to the seminal vesicles or bladder but not necessarily to the bones. Metastatic disease means the cancer has spread to lymph nodes or other sites such as bone, lung, and liver, and it’s treated differently than localized disease.4

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 53 Partin Tables

Partin Tables, arranged by tumor stage, Gleason score, and initial PSA level, predict the chance of the cancer being outside the prostate capsule, in the seminal vesicles, or in the lymph nodes. Named after one of the table’s original developers, Dr. Alan Partin of Johns Hopkins University, the Partin Tables were created by evaluating the pathology results from radical prostatectomy patients and comparing the results with the preoperative PSA levels, Gleason scores, and stage. Based on this information, the likelihood of spread into and through the edge of the capsule, into the seminal vesicles, or into the pelvic lymph nodes was determined for individual groups of patients. It should also be noted that other reputable groups have developed similar tools providing comparable information).76

The Partin Tables can be a useful starting point when considering treatment options, but they do not predict cure. Their aim is to take an educated guess about whether the cancer is completely confined to the prostate or if it’s spread to or through the capsule, reached into the seminal vesicles, or extended to the nearby lymph nodes. Neither do the tables predict this with 100 percent accuracy for any individual patient. The tables just give the likelihood based on information from a large group of patients.77

The Partin Tables also do not predict for disease outside of the surgical margin or the margin of the radioactive implant. When the prostate is removed, the surgeon will often take an extra bit of tissue - a margin - from around the prostate. In radioactive seed implants, the margin is an area of tissue, about 5 to 10 millimeters, beyond the gland that the radiation also reaches.78

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 54 The Partin Tables don’t take into account all of the factors that may predict the extent of tumor. Here’s an example: Let’s say there are two patients, both with a Gleason 6 cancer, stage T1c, and a PSA of 8.0 ng/mL; one patient has 7 out of 10 cores that are positive for cancer, while the other patient has only 1 out of 10 positive cores. The patient with the seven positive cores probably has a high likelihood of cancer spread beyond the capsule. Knowing the possibility of any or all of the above may impact treatment recommendation(s).76

Prostate Cancer Treatment Options

There are a number of treatment options for individuals who have been diagnosed with prostate cancer. The specific treatment used will depend on a number of factors, including the severity of the cancer, the patient’s age, and overall health. Upon diagnosis, the practitioner will assess the patient and determine an appropriate course of action. In some instances, the medical practitioner will take a wait and see approach, while other situations may warrant more aggressive treatment.

American Urological Association Recommendations and Current Guidelines

Current guidelines from the American Urological Association (AUA) recommend that the initial evaluation of and treatment discussion with a patient with prostate cancer focus on the following two factors:

1. The patient’s overall life expectancy (as determined by age and comorbidities) and overall health status.

2. The biologic characteristics of the tumor, together with its predicted aggressiveness and behavior. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 55 The AUA guidelines recommend that decisions regarding treatment take into account the preferences of the patient for the various treatment options, with consideration of complications, adverse effects, relative efficacy, and quality-of-life issues. Health-related quality of life is a particularly important concern for patients with clinically localized prostate cancer.

Standard treatments for clinically localized prostate cancer include the following:  Active surveillance  Watchful waiting  Radical prostatectomy  Radiation therapy  Hormone therapy  Cryotherapy is also used, but long-term survival studies are lacking.

Newer therapies, such as proton-beam radiation and high-intensity focused ultrasound are being used, but long-term survival and complication rates have not been presented in well-done studies.

For locally advanced prostate cancer, radiation therapy along with androgen ablation is generally recommended, although radical prostatectomy may be an appropriate alternative to radiation therapy in some cases. A combination of external radiation, brachytherapy, and hormone therapy is also being used, but it is unclear whether it offers advantages over hormone therapy and external radiation alone, and it does increase complications.

Metastatic prostate cancer is rarely curable. Management of these cases typically involves therapy directed at relief of particular symptoms (i.e., palliation of pain) and attempts to slow further progression of disease.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 56 Comparisons between treatments for prostate cancer are complicated by the stage-migration and lead-time bias associated with the adoption of prostate- specific antigen (PSA)–based screening and the resultant increase in the detection of small, clinically localized cancers. In addition, treatment selection has become more complicated as options have increased.

Surgical treatment currently includes nerve-sparing techniques, laparoscopic procedures, robotically-assisted procedures, and the classic retropubic prostatectomy and perineal prostatectomy. Additionally, multiple forms of radiation therapy are currently available. These include the following:  Conventional radiation therapy  Three-dimensional (3-D) conformal radiation therapy  Intensity-modulated radiation therapy  Temporary and permanent brachytherapy  Proton-beam radiation  Stereotactically-guided radiation

Hormone therapy for prostate cancer is also known as androgen deprivation therapy (ADT). It may consist of medical castration. Agents used for medical castration include luteinizing hormone–releasing hormone (LHRH) analogues or antagonists, antiandrogens, and other androgen suppressants.75 Surgical castration (orchiectomy) would be another option.

Watchful Waiting

Watchful waiting, as the name implies, is the alternative of monitoring prostate cancer and postponing therapy - perhaps temporarily, perhaps permanently. Although the common term is watchful waiting, medical providers might call it by different names, including expectant management, conservative management, observation, or surveillance.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 57 In a large population-based study of overall survival of men aged 50–79 treated by various methods, the 10-year prostate cancer specific survival rate for men with grade 1 cancer was 93 percent after conservative management, 94 percent following prostatectomy, and 90 percent after external beam radiation. Authors of a commentary that appeared in Journal of the National Cancer Institute note that large population based studies show that the 15-year survival rate for appropriately selected men who are on watchful waiting is similar to the survival rate of men in the same age range who do not have prostate cancer.79

Although there are studies showing that men are unlikely to die from their prostate cancer if it is initially untreated, they do not tell whether a man may have suffered as it progressed. Treatment at the time of cancer progression may slow the cancer enough that the patient dies of some other cause.80

Simply because a patient’s prostate cancer is not being treated doesn’t mean it’s being ignored. Watchful waiting is active surveillance. It’s a way for the patient and his provider to get a sense of how rapidly the disease is, or is not, progressing. As mentioned, regular prostate specific antigen (PSA) tests and digital rectal exams (DREs) are the standard methods to monitor the disease, but occasionally providers may recommend repeat biopsies or other tests periodically to check if the cancer is progressing.81

There are several reasons one might choose watchful waiting. One of the strongest motivators for this choice is the chance to avoid the possible side effects of available treatments. Two of the most common and bothersome side effects are incontinence and erectile dysfunction (ED). Concern about developing one or both of these side effects is understandable, since the

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 58 prostate lies in the middle of critical junctions for sexual and urinary functions. Each of the current treatment options can affect these functions at different rates and in different ways depending on the therapy, the provider’s skill, and the patient.82 The following is a patient scenario in which watchful waiting might be employed:83

Patient Scenario: 81 year-old Assume that an 81-year-old man diagnosed with early stage prostate cancer is contemplating watchful waiting. His doctor determines that his cancer is not aggressive and that he has reliable urinary control but is unable to achieve a good erection. This patient also experiences other health problems, including type 2 diabetes and cardiovascular problems. Given that he might not live 10 more years (the benchmark doctors use in determining whether a patient will benefit from treatment) and the poor condition of his overall health, watchful waiting could be a solid choice because it would preserve his current quality of life, including the existing good urinary function. What if during his remaining years the cancer progresses to the point of needing treatment?

He then faces the prospect of more aggressive treatment with a lower chance of success (and a higher chance of side effects) than he would experience if he were to get immediate treatment. After careful thought, this patient and his doctor agreed that watchful waiting would be a reasonable approach. Many prostate cancers grow so slowly that the disease can be monitored with regular PSA tests and DREs, and they may never progress to give the patient any problems.

It is important to note that more aggressive cancers (those with higher Gleason scores) are usually not good candidates for watchful waiting. Even in older men, the cancer cells can spread and cause symptoms in just a few years. Ordinarily the best candidates for watchful waiting are patients whose Gleason scores are less than or equal to 6. Cancer that is scored Gleason 8 to 10 almost always needs treatment, and Gleason 7 prostate cancer falls in between. In our 81-year-old’s case, his doctor’s concern about preexisting health conditions outweighed the need for immediate prostate cancer treatment.

The doctor recommended, and the patient agreed, that he would get a PSA test every three months and a repeat biopsy in one year. They also agreed that during monitoring, if the patient’s cancer was clearly progressing, then they would revisit the possibility of treatment. Monitoring with PSA during watchful waiting is simple, but it must be done frequently enough to check if the cancer is progressing rapidly. So, that’s a downside of watchful waiting: the patient has to commit to a lot of visits to the doctor and repeated testing.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 59 There are several factors that must be considered when choosing watchful waiting. The first is overall health. If the patient is too ill to benefit from cancer treatment, he might be a candidate for watchful waiting. For example, if a patient has suffered multiple heart attacks and still has an unstable heart when he’s diagnosed with low-grade, low-stage prostate cancer, he may choose watchful waiting until his condition improves.80

There is no hard-and-fast rule about how old a patient has to be in order to contemplate watchful waiting, but age is another consideration. Generally, men younger than 65 have a relatively long life expectancy and are more likely to have the prostate cancer progress during their lifetimes. Men in this age bracket usually select a curative treatment. However, patients in their early 80s with low-grade tumors and low PSAs often consider watchful waiting as an option because of this age group’s shorter life expectancy. The tumor grade and stage are the third and fourth factors. Older men with low- grade and low-stage tumors are the best candidates for watchful waiting.84,85

Another aspect of watchful waiting pertains to the psychology of having cancer. One of the difficulties with watchful waiting is the knowledge that a cancer is present but whether it is progressing may be unknown to both the medical provider and the patient. Frequent visits and assurances from the provider can help alleviate this fear of the unknown. But, in truth, watchful waiting has been difficult for some patients - especially those who tend to focus on and think about their cancer daily. It is these patients who find watchful waiting to be a burden, and each follow-up with the provider becomes an anxiety- filled experience. If watchful waiting is significantly affecting the quality of a patient’s emotional and mental wellbeing, then it may be time to consider treatment84,86

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 60 While the PSA value typically measures the status of the cancer, it cannot be relied upon completely to determine candidacy for watchful waiting. For one thing, PSA levels can be influenced by prostate conditions other than cancer. Also, high-grade tumors may produce PSA at a very low level. Many factors - stage, grade of the tumor, and the number of positive biopsies, as well as the PSA - should weigh into the decision for or against watchful waiting. In most instances, patients see their medical providers at least every six months. In the early stages after diagnosis, it may be appropriate to visit the provider more frequently, perhaps every three months. While most watchful waiting patients see their providers twice a year, the best advice for each patient is to work closely with his own provider to establish a suitable schedule.87

Advantages

The chief advantage is that patients who qualify for watchful waiting can delay or entirely avoid side effects from treatment. Patients who are elderly, who have serious medical conditions, and/or who are sexually active may choose watchful waiting because of their desire to maintain their current quality of life for several more years before treatment is necessary. In addition, if a patient makes positive lifestyle changes — getting more exercise, decreasing saturated fats, avoiding excessive calories, and incorporating more fruits and vegetables into his diet — will enhance the patient’s health. That can add to his overall wellbeing during the months (or years) of watchful waiting.88

Disadvantages

Occasionally, the tumor progresses rapidly. There are also uncommon cases in which the patient is not monitored carefully and the tumor advances to a higher stage or grade. Tumors that become larger may require more nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 61 aggressive treatment and, consequently, a greater number and higher degree of side effects, plus a possibility of the treatment being less effective. The provider will employ all of his or her experience and use the best testing technology in making an estimate of the cancer’s aggressiveness. Usually, the estimate is right. But it’s impossible for any provider to predict with 100 percent accuracy if or how rapidly a cancer will progress.87

Treatment Considerations

If the PSA rises above 10 ng/mL (and certainly 20 ng/mL) the cancer is less likely to be confined just to the prostate. If the PSA increases to these levels during watchful waiting, treatment will probably be considered, even if the patient is of advanced age or has other health conditions. The rate of rise of PSA may also influence the decision to reconsider treatment, but there are no widely accepted standards.89

A change in the Gleason score is another factor that favors treatment. If a cancer was Gleason 5 but a repeat biopsy revealed a change to Gleason 7 or higher, this data might prompt us to recommend a new course of action. Even with a rising PSA, an increased Gleason score, or a new nodule felt during a DRE, the patient may still decide to decline treatment. It is valuable for the patient and his provider to agree on the point at which treatment should be considered. Therefore, it is important for each patient to develop a trusting relationship with his provider and work closely with him or her during the watchful waiting program to determine when, or if, to seek curative therapy.99

Prostatectomy

Removing the prostate (the medical term is prostatectomy) has been a mainstay of prostate cancer treatment since the early 1900s. But one of the nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 62 problems with these early approaches was excessive blood loss.87 It wasn’t until the 1970s that surgeons at Johns Hopkins solved this dilemma. They were the first to tie off the major veins of the prostate and bladder to stem the disproportionate blood flow. Less blood in the surgical field meant they had an improved view of what they were doing. Patients began to fare better immediately. The 1980s brought another improvement when surgeons introduced the nerve sparing prostatectomy. Since these two developments — better blood control and the ability to spare nerves responsible for erection — prostatectomies have had a resurgence in popularity as a treatment for prostate cancer.49

Radical Prostatectomy Options

The most common ways to remove the prostate are the radical retropubic, perineal, and laparoscopic techniques. The radical retropubic approach - so named because the prostate lies behind the pubic bone - requires a large abdominal incision. During the delicate operation, the surgeon may remove a sample of the pelvic lymph nodes and send them to a pathologist for an immediate preliminary evaluation. If the nodes are cancerous, often the surgeon will stop the procedure and not remove the prostate. This is because the cancer has already spread to the nodes, and most evidence suggests that removing the prostate when the cancer has spread to the lymph nodes will do no good in achieving a cure. (The primary treatment option for patients with positive nodes is immediate and continuous hormonal therapy). If the lymph nodes are not cancerous, the surgical team continues its precise task of removing the prostate, the portion of urethra contained within the prostate, the seminal vesicles, and the vas deferens from the surrounding tissue. The final step is reattaching the bladder to the urethra.91

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 63 Eligibility for Surgery

Surgery is not recommended when patients are a poor operative risk because of other health problems. The most significant factors for predicting success are age and overall health. The major factor precluding surgery is if the patient’s life expectancy is less than 10 years; patients over 75 years old are generally not considered for radical prostatectomy. Health factors affecting tolerance to a major surgery must also be considered. Obesity is a factor in whether or not radical retropubic prostatectomies can be performed, but obesity is not generally a problem in radical perineal or laparoscopic prostatectomies.92

When the cancer has extended past the prostate, there’s less chance of successful treatment with a single therapy, including surgery. However, there is a small group of surgeons who offer surgery on an otherwise healthy patient with locally advanced prostate cancer, and even in patients with high risk of lymph node involvement. This is a controversial practice, but there is some limited experience in doing surgery on advanced prostate cancer. It should be noted that most patients with locally advanced, nonmetastatic prostate cancer undergo external beam radiation therapy plus hormonal therapy.75 The following table outlines the various surgical procedures involving prostatectomy.93-95

Prostatectomy Surgical Procedures Perineal With a perineal prostatectomy, the surgeon makes the incision Prostatectomy between the anus and the scrotum. The advantage of perineal prostatectomy compared to retropubic surgery is that patients tend to experience less blood loss, less trauma to the body, and less pain, and they heal somewhat faster. Most patients go home in one to two days. However, one downside of perineal prostatectomy is that it’s next to impossible to remove pelvic lymph nodes for testing. If the surgeon wants to evaluate the lymph nodes during a perineal prostatectomy, he or she must make another incision in the abdomen.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 64 Fortunately, the majority of contemporary patients have less than 1 percent chance of positive lymph node involvement, making the perineal approach acceptable.

Laparoscopic A laparoscope is a slender, tubelike instrument that allows the Prostatectomy surgeon to see into small areas and perform surgery. Instead of making a single, long abdominal incision, the urologist makes several small ones and uses the laparoscope and other instruments to remove the prostate.

The chief advantages of laparoscopic prostatectomies are quicker recovery and less abdominal pain compared with a standard radical prostatectomy.

Laparoscopic prostatectomies are difficult, though, and surgeons must perform many cases before they develop enough skill to do the procedure efficiently and with the fewest possible side effects. Moreover, it will be several years before we know the scientific results and advantages of laparoscopic radical prostatectomy. Little is published regarding the likelihood that the laparoscopic approach will remove all the cancer and result in the same 10-year disease control rates that standard radical prostatectomy or radiation therapy achieves.

Nerve Sparing Neurovascular bundles lie on both sides of the prostate, just outside Surgery of the capsule. In select patients with small cancers, urologists leave one or both of these bundles intact in hopes of maintaining erectile function. Not every patient who chooses a radical prostatectomy is a good candidate for the nerve-sparing procedure, though. It’s most effective in men with only the smallest of tumors. Men with large tumors or cancer in both prostate lobes are generally poor candidates for nerve-sparing surgery. Larger tumors have a greater risk of having positive margins. A surgical margin simply means the edges of the tissue. When the prostate is sent to the lab for tests, one of the things the pathologist looks for is whether cancer cells are on the edge of the cut tissue. A positive surgical margin means that cancer is found at the margin - or edge - of the specimen. A negative margin means the cancer was likely contained entirely within the prostate.

A man with cancer at the apex of the prostate is also a poor candidate for nerve sparing surgery. Similarly, a patient who is already experiencing erectile dysfunction is discouraged from the nerve-sparing operation. In this case, the nerve- sparing procedure is not going to increase this man’s chance of having erections. Even if everything looks good for a nerve sparing surgery and the patient and his surgeon choose this option, it’s only during the operation - once the surgeon sees the tumor’s extent - that he or she will make the final decision whether to leave one or both neurovascular bundles intact. Also, maintaining erectile function not only depends on maintaining the integrity of the nerves responsible for an erection, but also the blood sup- ply to and from the penis. The prostatectomy might alter the patient’s blood supply so that even if his nerves were kept, he still might not be able to have erections. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 65 Sural Nerve A sural nerve graft is performed during a radical prostatectomy. The Graft surgeon detaches a portion of the sural nerve from the patient’s lower leg, near the ankle, and grafts this in place of the removed erectile nerves. Sural nerve grafts are primarily used for men whose surgeons deliberately excise (remove) the nerves because of extent of the tumor.

Preliminary data shows that grafting a nerve may improve erectile function, but there’s a great deal of debate about whether this is effective. The procedure has been around for only a few years, it’s not performed routinely, and studies so far have focused only on a small number of patients.

There are a few downsides to a sural nerve graft. It adds about 45 minutes to a radical prostatectomy, so the patient has to be under anesthesia for that much longer. A second incision, this one on the leg, must also heal. The man will also lose sensation in a small area on the outside of the foot.

The patient will undergo one of the procedures above depending on his specific needs and treatment requirements. There are some advantages to retropubic radical prostatectomies compared to other approaches, including the ability to remove a select few lymph nodes to test for cancer and possibly leaving one or both of the nerve bundles. Another primary advantage with radical retropubic prostatectomy is that surgeons are often able to remove more tissue, which means a greater chance of removing all of the cancer. In cases where positive surgical margins remain after surgery, additional therapy including radiation therapy, hormonal therapy, or both, may be considered.96

In terms of advantages for radical perineal prostatectomies, patients have less blood loss and tend to recover quicker. Most comparative studies show that radical perineal prostatectomy has similar cancer control compared to radical retropubic prostatectomy. Continence and potency data between the

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 66 two are also the same. A nerve-sparing technique can also be done with a radical retropubic or a laparoscopic prostatectomy.93

Recovery

Patients spend up to three days in the hospital before going home. While some studies show that patients can get back to work in several days, it is typically a few weeks before they’re back on the job. An important determinant is the type of job the patient has and the type of prostatectomy he undergoes. For instance, a patient in a comparatively nonphysical profession will be able to return to work earlier than one with a physically demanding profession.97,98 For a man who has a much more physical job, his ability to return to work will be different - even with a perineal prostatectomy. The incision needs four to six weeks to heal before the patient can put physical stress on it. So, men in physically challenging professions are likely to be off work longer before they can resume their usual posts.99

Advantages

This approach can indeed cure prostate cancer. For most patients, the cure rates of radical prostatectomy are comparable to other approaches, particularly radiation therapy. Many patients choose prostatectomy because of a desire to have all of the cancer removed immediately. To achieve this, they want to remove the cancer-harboring organ from their bodies (which surgery does in the majority of cases). Another potential advantage is that because a pathologist examines the removed prostate, the extent of the cancer can be determined. This postsurgical pathological examination allows for the recommendation of additional treatments if needed.100

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 67 Risks and Side Effects98

 Risks: In radical prostatectomy, damage to the bladder and the rectum can occur. The patient may experience adverse reactions to anesthesia or other medications. Life-threatening trouble with major organs (such as the heart and/or the kidneys) during surgery can also take place, especially if those organs are already weak from existing disease — but this is infrequent.

Death can occur, though it is very rare. Each year in the United States, between 0.1 percent and 0.7 percent of patients die during radical retro pubic prostatectomies. It appears that risk of mortality is associated with age. Figures show that the death rate from prostatectomy in men 65–75 years old is less than 1 percent, but in men older than 80 the mortality rate nears 5 percent. Blood loss is often minimal and transfusion rates have fallen over the years.

 Side Effects:

 Erectile Dysfunction: Whether a man chooses external beam radiation or radical prostatectomy, his chance of developing ED appears to be about the same — at least according to one study looking at 802 men. Sixty-nine percent of these men reported normal erectile function prior to treatment. About 50 months after treatment, 10 percent of patients who had radical prostatectomy reported normal erectile function. Fifteen percent of men in the radiation group reported normal functioning. On the other hand, nearly 40 percent of men who were on watchful waiting still had adequate erections six months later. Other studies, however, have shown nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 68 that radiation therapy is less likely than surgery to cause ED, but further research on this topic is necessary.

Erectile dysfunction frequently occurs after nerve-sparing surgeries, too. The risk of ED doesn’t appear to depend on whether the surgeon saves one nerve bundle (unilateral nerve- sparing surgery) or both neurovascular bundles (bilateral nerve- sparing prostatectomy).

One study asked men to fill out a questionnaire about their sexual and urinary functions before surgery and then had them answer the same questions at 3 and 12 months later. One year later, about 80 percent of patients who had bilateral nerve sparing surgery reported inadequate erections. Those who had unilateral nerve sparing surgery fared about the same. This, despite the fact that patients who underwent bilateral and unilateral nerve sparing surgeries tended to be younger and had less advanced cancers than those who had standard radical prostatectomies.

Conversely, in a study out of Johns Hopkins, 86 percent of the 64 men who had bilateral nerve-sparing surgery achieved erections 18 months after surgery. About one-third of these men used Viagra. Bear in mind, however, the average age of men in this study was under 60. Age plays a big role in a return to erectile function, no matter what the treatment. The younger the patient, the better his chance of maintaining erections.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 69  Urinary Incontinence: There’s no doubt that a man’s urinary continence is going to be different, because surgery removes a portion of the urethra responsible for some of the urinary control. Stress incontinence (leaking a few drops of urine during sneezing, coughing, or lifting heavy objects) occurs just after the catheter is removed, which is from 10 days to two weeks following surgery. After the catheter is removed, stress incontinence occurs for weeks or months simply because the remaining sphincter muscle is not yet strong enough to retain all of the urine in the bladder.

Many patients report regaining most of their continence after three months, but it can take up to a year. One year after surgery, nearly 92 percent of 593 patients treated at one center of excellence experienced complete continence, 8 percent reported mild or moderate stress incontinence, and 0.3 percent had severe incontinence. Unfortunately, not all urologists have this degree of success. In one study, 24 months after surgery 9.6 percent of men reported either having no control or often dripping or leaking urine, 13.8 percent reported leaking at least twice per day, and 28.1 percent of respondents said they wore pads to keep dry.

The age at which a man undergoes radical prostatectomy plays a role in urinary incontinence; the older the patient, the greater the chance of incontinence. The good news in all of this is that most men who participate in quality of life studies report incontinence does not affect their lifestyle.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 70 External Beam Radiation Therapy

During the past 90 years, radiation for prostate cancer has evolved from an imprecise therapy into highly sophisticated treatments that use linear accelerators, proton beams, neutron beams, and radioactive seeds for implants. External beam radiation came into its own as a prostate cancer treatment during the 1950s and 1960s with the introduction of cobalt therapy. Cobalt-60 radiation appeared at first to cure as many cases of prostate cancer as surgery without serious side effects. However, researchers soon found that cobalt radiation carried its own set of adverse effects. This knowledge led to the development of linear accelerators, which allowed for higher doses of radiation but with generally fewer side effects than the old cobalt-60 treatments.

The technical advances in prostate cancer radiation therapy in the last few decades have also decreased the rates of urinary incontinence, erectile dysfunction (ED), and other side effects. These advances, coupled with evidence that modern techniques appear to be as effective as prostatectomy in curing early stage prostate cancer, make radiation a convincing choice for successful prostate cancer treatment. Although precise numbers are not yet reported, it is likely that 50 percent or more of U.S. prostate cancer patients each year receive either seeds or external beam radiation therapy as part of their treatment regimen.104

Every type of cell in the body has its own cell cycle time. For example, the cells lining the mouth have about a 48-hour cell cycle time; they replace themselves within two days. Normal, noncancerous prostate cells are not as short-lived. They have very long cell cycle times, as do some prostate cancer cells. Radiation treatment impairs a cell’s ability to undergo mitosis by damaging the cell’s DNA (which is an abbreviation for its chemical name,

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 71 deoxyribonucleic acid). DNA resembles a ladder. The radiation pops holes into the sides of the ladder so that after a time only the rungs are holding the ladder together. When it comes time to divide, the rungs separate just like they’re supposed to, but the ladder crumbles because of the many holes in the ladder’s sides. The cell dies because the DNA (in our analogy, the ladder) simply breaks into tiny pieces.105

Patients treated for prostate cancer with external radiation get daily treatments, Monday through Friday, for eight to nine weeks. This divides the total dose of radiation into small daily amounts, or fractions (which is why it’s called fractionated radiation therapy). Normal prostate cells are much more effective at repairing the radiation damage to their DNA than prostate cancer cells. Thus, these smaller hits of radiation allow the noncancerous tissue to repair itself after radiation. Most cancer cells don’t recover well after being hit with radiation, even when it’s given in small doses such as those of fractionated radiation therapy.106

Photon, proton, and neutron radiation are types of radiation that are delivered by machine. Seed implantation is also radiation but it is delivered internally. Low-energy photon radiation is also known as x-rays, such as a chest x-ray. The energy and amount of this radiation is low enough to penetrate the body to create x-ray images, but it’s too low to damage any significant number of cells.121

High-energy photon radiation is produced by a linear accelerator, is more potent than low dose x-rays, and is capable of killing cancer. With this treatment, the patient lies on a special treatment table as the linear accelerator rotates above and around the prostate area to deliver the radiation.107

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 72 Eligibility

Candidates for surgery or seed implantation are also usually good candidates for external beam radiation. It is also a good option for patients with an aversion to any kind of invasive procedure, patients who are too old for surgery, and men who are not good candidates for seed implants because of urinary difficulties due to benign prostatic hyperplasia (BPH).109 Of all the treatments for prostate cancer that’s confined to the gland — surgery, seed implantation, or external beam radiation — external beam is applicable to the largest range of patients. This is because the treatment is noninvasive and does not involve anesthesia or surgical time. Thus, patients who are in relatively poor health can easily tolerate this form of therapy. However, patients who have preexisting conditions of the rectum or colon, such as inflammatory bowel disease, are not good candidates for external beam therapy.110

Patients who have a history of multiple abdominal surgeries often have considerable scar tissue within their abdomens, which may make the colon and intestines more susceptible to external beam radiotherapy damage, particularly if pelvic radiotherapy is given. If patients have received any prior radiation therapy to the pelvic region for other cancers, further radiation usually cannot be used — but a qualified radiation oncologist should evaluate each case to establish this with certainty.117

Unfortunately, high-grade cancers are not as likely as low-grade cancers to be cured with any single treatment method. For that reason, there is ongoing research to determine which local treatment or combination of treatments — such as radiation or surgery combined with hormone therapy or — are best. External beam radiation alone, however, can cure 15 percent to 30 percent of men who have high-grade prostate cancer.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 73 More recent results from large clinical trials demonstrate that the combination of hormonal therapy with radiation offers better cure rates than older conventional radiation therapy alone.

Patients who have existing erectile difficulties will have a greater chance of erectile dysfunction following any treatment, including external beam. So, there is no particular reason to favor external beam therapy in patients who have existing erectile difficulties. Some providers feel that patients who have a lot of urinary problems usually associated with BPH in addition to their prostate cancer might be better off with external beam radiation rather than seed implantation. This is because external beam radiation tends to be a bit gentler on the prostate than seed implantation. But for those younger patients who have prostate cancer along with BPH that’s causing a lot of urinary symptoms, surgery might be recommended because it would address both problems.

With a transurethral resection of the prostate (TURP), a portion of the prostate around the urethra is removed to improve urinary flow. This operation causes scar tissue to form and leaves a small cavity in the upper part of the prostate. Some providers feel that the slight damage caused by the TURP operation can increase the risk of bleeding or incontinence following radiation treatments. Since external beam radiation is the most “gentle” form of radiation therapy for the prostate, it may be the preferred method of treatment for patients who have had a previous TURP.111

Other Types of Radiation Therapy

Three-dimensional Conformal Radiation Therapy (3D –CRT)

The goal of three-dimensional conformal radiation therapy (3D-CRT) is to deliver a higher dose of photon radiation while preserving more of the nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 74 surrounding normal tissue. Three-dimensional conformal radiation therapy uses the photon energy from a linear accelerator, but special software is used to plan and deliver the higher radiation doses with greater accuracy. This planning is applied to detailed cross-sectional images of a patient’s internal anatomy. The imaging, usually done with a CT scanner, allows for the precise identification of the prostate and normal adjacent structures, such as the rectum and bladder.112

With 3D-CRT, the patient lies on a treatment table just as if he is to receive normal photon radiation, but the radiation beam in each of several fields is matched to the shape of the prostate while avoiding much nearby anatomy. This means the prostate receives the strongest dose of radiation, with less radiation striking the rectum and bladder. Virtually all radiation treatment centers in the U.S. use 3D-CRT, and it is estimated that within three to five years most centers will be using a more advanced form of 3D-CRT known as intensity modulated radiation therapy (IMRT), as some centers do now.

Intensity Modulated Radiation Therapy (IMRT)

Intensity modulated radiation therapy is a form of 3D-CRT radiation therapy. Just as in 3D-CRT, the prostate is treated with photon radiation from multiple angles every day. Yet the IMRT beam strength (intensity) can be modified (modulated) in every beam. In other words, a portion of the beam can be stronger in one area and weaker just fractions of a centimeter away. The radiation beams are shaped and modulated using a computerized device known as a multileaf collimator (MLC), which is positioned at the point where radiation exits the linear accelerator. The MLC controls the shape, size, and timing of the beams. This allows even higher doses of radiation to be delivered to the prostate while maintaining low doses to the normal tissue.128 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 75 Intensity modulated radiation therapy is proving to be an excellent way of delivering radiation to the prostate while decreasing the rate of side effects associated with the other types of external beam radiation. At Memorial Sloan-Kettering Cancer Center, a study of 772 prostate cancer patients who received IMRT between 1996 and 2001 showed a significant decline in the number of men who experienced rectal problems compared to what’s been seen with 3D-CRT. Also, the short-term PSA control rate appeared to be about equal to the results of 3D-CRT radiation. Thus, IMRT seems to provide PSA control rates similar to 3D-CRT with fewer immediate and long-term effects to the rectum.113

Proton Beam Radiation

Proton radiation is particle radiation. Unlike photon radiation — which is a wave that gives up most of its energy as it enters the body and whose strength decreases approximately evenly as it travels through tissues — proton beam radiation deposits its energy only as the particles begin to slow down. The distance that a proton of a given energy travels in human tissue before it slows down is well known. So, by positioning the beam depth to deposit its energy only in the cancerous tissue, doctors hope to avoid many side effects often associated with radiation therapy. Proton radiation is ideal for cancers that require exceptionally delicate treatment, such as a tumor that wraps around the spinal cord or the optic nerve.114

Radiation oncologists rarely use proton therapy as a sole treatment for prostate cancer. In those men who do receive it, it’s most often combined with standard or conformal external beam radiation. The patients typically receive five weeks of standard or 3D-CRT radiation to the prostate, seminal vesicles, and possibly the lymph nodes, followed by two to three weeks of proton beam radiation to the prostate only. There is some controversy nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 76 regarding the value of proton therapy for prostate cancer, particularly since the equipment cost is typically more than ten times greater than conventional 3D-CRT and IMRT-based photon therapy from a linear accelerator.115

Neutron Beam Radiation Therapy

Neutron beam radiation therapy relies on subatomic particles – neutrons - to defeat cancer cells. Neutron therapy has been associated with a greater degree of side effects to tissues around the prostate. A few U.S. centers are investigating it as a treatment. Similar to the situation with proton therapy, more results are needed to make appropriate comparisons.

Treatment Process

While the techniques of delivering conventional, 3D-CRT, and IMRT treatments are slightly different, the way medical providers plan the treatment is generally similar. Planning begins with a CT scan of the prostate, from which the radiation oncologist outlines the treatment area. Next, a team of radiation physicists and dosimetrists (the medical personnel who specialize in planning radiation doses) design the treatment field.116

The target area conforms to the curve and shape of the patient’s prostate. A small area around the prostate, including some of the bladder and the rectum, also receives radiation but it’s mostly of a lower dose compared to what the prostate receives. This margin is by design because prostate cancer frequently spreads microscopically outside of the prostate and into the surrounding tissue. Such microscopic spread cannot be seen on diagnostic scans such as CTs or MRIs. The treatment margin ensures that the entire prostate is treated at every session. After the plan is completed, it’s submitted to the radiation oncologist for review and approval.117 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 77 Positioning is crucial in all types of external beam radiation. To make sure the photon radiation is right on target, the patient receives small, semi- permanent marks on his skin. Before each day’s session, the patient lies on the table and the technologists line up those marks to alignment lasers. These lasers are not at all harmful and are simply a means to make sure the patient is right where he needs to be for treatment.107

There are a number of studies showing that each day the prostate can be in a slightly different internal position. This may be due to the fullness of the bladder and rectum as well as the patient’s position on the treatment table. The treatment is designed to compensate for this prostate movement by treating a margin around the gland. Another method to ensure the correct area is treated is to use daily ultra-sound localization of the prostate. When the patient is on the treatment table, a special ultrasound machine is used to determine the prostate position on that particular day. This isn’t a foolproof method and although a number of centers are doing it, it’s still being investigated to determine just how effective it is.105,118

Another way of checking the prostate position calls for placing small metallic markers in the prostate prior to radiation therapy. A daily x-ray determines the positions of these markers, and the treatment team makes sure these markers fall within that day’s radiation treatment. This method has not been widely adopted yet because it’s still being studied, but it is showing great promise.

Finally, physicists and researchers from linear accelerator manufacturers and elsewhere are looking into ways that these machines can use the linear accelerators to show the position of the prostate and other organs adjacent to the prostate on a daily basis as the patient lies on the treatment table. It

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 78 is thought that this will be a reliable method of compensating for prostate movement and give medical providers a better ability to deliver radiation at higher doses and with smaller margins. It is anticipated that such approaches will allow even higher doses of radiation to be delivered to the prostate and thus result in higher cure rates with fewer side effects.106

Treatment Selection

The choice for therapy doesn’t depend primarily on the provider’s recommendation. The patient plays an important role in making this decision, too. For instance, some men who are candidates for radioactive seed therapy don’t want permanent seeds and instead opt for external beam radiation. What the patient’s insurance plan will cover, too, can be a factor.

Other dynamics influencing the kind of external beam therapy the provider may recommend is what’s available at the radiation center where he or she practices and the goal of the therapy. The goal of therapy would be whether the providers want to treat the prostate only, prostate plus seminal vesicles, or the pelvis. The therapeutic goal also takes into account the desired dose — lower dose for small cancers, higher for large cancers — and whether brachytherapy will be part of the overall treatment.105

Advantages

With this therapy, patients avoid the risks commonly associated with surgery — adverse reaction to anesthesia, the potential for having to undergo a transfusion, and the time needed to recover from a surgical wound. Generally, no pain is associated with radiation therapy. Another benefit is that the immediate side effects are mild and generally do not limit day-to- day activities. Unlike surgery, the risk of urinary incontinence is very low,

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 79 and external beam radiation is associated with fewer temporary initial urinary symptoms than seed implantation.111

Disadvantages

A full course of treatment requires eight weeks or more of daily visits to a cancer treatment center, five days per week for about 15 to 35 minutes each day. The rectum and colon are the most susceptible organs to be damaged from external beam radiation; between 5 percent and 15 percent of patients develop rectal problems. Another potential — and controversial — disadvantage to external beam therapy is the radiation dose itself. The effective radiation dose delivered to the prostate via external beam is less than it is with radioactive seed implants.

Retrospective studies in which patients are biopsied several years after receiving any form of radiation therapy tend to show residual or recurrent prostate cancer more frequently in patients who had external beam radiation than in patients with seed implants. It’s important to note, however, that while there may be a higher incidence of recurrence with external beam, these retrospective studies do not necessarily show that there’s a greater risk of developing a life threatening recurrence. Therefore, without direct head-to-head clinical trials it is difficult to state with certainty whether there is any difference between external beam radiation therapy and seeds when it comes to curing prostate cancer.

For most men diagnosed with early stage prostate cancer, when each treatment is done appropriately and with modern techniques, each offers a very high cure rate with a very low chance of dying from prostate cancer within 10 to 12 years of treatment.109,116

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 80 Side Effects

Prostate cancer patients have few, if any, side effects during the first weeks of external beam radiation. As time goes on, though, they’re likely to begin experiencing bowel and bladder symptoms. A significant portion of patients develops urinary urgency and frequency after a few weeks of treatment. Many patients also report some rectal urgency and increased frequency of bowel movements. Patients may experience temporary rectal irritation that could result in more frequent bowel movements, a bit of soreness in the anal area, or diarrhea. These symptoms usually resolve in a matter of a few weeks or a few months, but a small proportion of patients may be left with some permanent bowel problems.119

For patients with high-grade, more aggressive disease, it is often common to apply radiation to the pelvic lymph nodes in case the disease has spread. Because of the location of the pelvic lymph nodes, it’s impossible to avoid including some of the intestines in the radiation field. That’s why patients who have their pelvic nodes treated are more likely to experience more frequent bowel movements and perhaps diarrhea. These symptoms are usually temporary and sometimes it is suggested to use medication to help with these transient symptoms if they are bothersome.

Nausea that’s associated with radiation for prostate cancer is uncommon. Some patients experience a minor loss of pubic hair, although this is uncommon. Significant fatigue attributed to radiation treatment for prostate cancer doesn’t happen very often, but mild fatigue may occur. This usually goes away a few weeks after treatment ends. Radiation therapy, by itself, does not directly cause pain. However, it can irritate sensitive tissues such as the cells lining the rectum or hemorrhoidal tissue, which can lead to temporary rectal pain. If this symptom occurs, it’s often treated with

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 81 suppositories containing cortisone. Also, radiation can irritate the lining of the bladder or urethra to create some discomfort with urination. When this happens, over-the-counter pain medication may help, but many patients get by without any treatment because the irritation is usually mild and goes away within a few days to a few weeks after treatment.110

Long Term Effects

The rectum and bowel are the primary areas of concern following external beam treatments. In general, the older and simpler the radiation approach, the greater the chances of permanent bowel complications. The newer forms of 3D-CRT and IMRT treatments are less likely to leave the patient with long-term bowel difficulties, but there is always some risk.119-121

Primary Long-Term Effects Rectal Issues: Long-term rectal problems such as rectal bleeding (radiation proctitis) or a tendency for diarrhea have been reported in as many as 20 percent of patients or as few as 3 percent of patients, depending on the medical study and the degree of sophistication of external beam delivery. That being said, most radiation physicians would predict that somewhere between 5 percent and 10 percent of patients experience some bowel problem following conventional external beam radiation. The severity of these side effects is often mild.

Radiation proctitis can happen anywhere from six months to several years following treatment. Radiation proctitis may be evident only by small amounts of blood on the tissue paper following a bowel movement. Often this bleeding is so minor that it does not affect a patient’s blood count or require any therapy, and it usually goes away on its own. If radiation proctitis needs to be treated, it is best treated conservatively with suppositories, creams, and diet control. Typically, less than one out of 500 patients has rectal damage needing surgical repair. If a biopsy is taken from the area of radiation proctitis, that biopsy often aggravates the condition.

Urinary Issues: Another long-term problem that can occur has to do with urination. If an external beam patient is going to develop a long-term urinary side effect, it will more likely be urinary frequency and urgency (meaning patients need to get up more at night to urinate, and it’s difficult to wait for very long to relieve oneself) rather than leaking urine. If the bladder is damaged by radiation, blood in the urine can be seen.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 82 Similar to rectal bleeding, this side effect also happens months to years later and it recurs frequently. Occasionally, bleeding has to be controlled by an endoscopic procedure or medication. On rare occasions, the radiation can result in scarring of the urethra and lower bladder regions so that a narrowing of the urinary channel occurs, which may require surgery to open up the areas, but this only occurs in a very small percentage of men.

The development of incontinence following external beam radiation is not related specifically to the patient’s age. Incontinence is more common in patients who have had prior surgery, such as a TURP, or who have some weakness of their pelvic musculature, leading to difficulty with urination control. These factors are more related to a man’s general health than they are to his specific age, but typically the risk of developing any urinary incontinence following external radiation therapy is less than 1 percent.

Erectile Dysfunction: Erectile dysfunction (ED) is a common problem following external beam radiation. Its time of onset is a little longer than what occurs after surgery because it takes some time for the radiation to affect the vessels feeding blood to the erection mechanism. It is not uncommon for the onset of ED to occur six months to several years following external beam radiation. Since it’s rare that radiation therapy does complete damage to the nerves in charge of erections, radiation patients often respond to medication, such as Viagra, better than patients who had surgery. In most studies of erectile dysfunction following surgery, seed implantation, or external beam radiation, age has been found to be a contributing factor in the occurrence of ED.

As men age, it is common for erection ability to decline, become weaker, and, therefore, be more likely to be damaged by any treatment including external beam radiation, although this has not been studied thoroughly. If patients have other medical problems, such as diabetes or cardiovascular disease, most studies indicate that they, too, will be more susceptible to ED following any treatment. So, it would appear that the patient’s level of sexual functioning prior to therapy is probably more important than his exact age.

Sexual potency in men can be influenced by a number of factors including age, medication use, tobacco use, and overall health (including cardiovascular problems, diabetes, and hypertension). Because so many factors affect potency, it is difficult to measure the precise effect that radiation therapy may have on a man’s sexual potency. Current figures indicate that 10 percent to 50 percent of men may develop some degree of erectile dysfunction following radiation therapy, which may be temporary or long lasting. Nevertheless, some studies show there is good news for men with good sexual function prior to radiation therapy who develop some limitations afterward. Viagra can help 80 percent to 90 percent of them maintain sexual function.

Ongoing Monitoring Following Radiation Treatment

Follow-up after radiation treatment is not significantly different than follow- up after surgery. In both instances, PSA measurements are the cornerstone nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 83 of the checkups. However, the PSA response following either radiation or seeds acts somewhat differently than it does after surgery. Surgery should completely remove the prostate and the prostate cancer. Therefore, the PSA is expected to drop to very low levels, usually undetectable, within three weeks of the surgery. But after radiation, the prostate gland can produce some PSA as the radiation is destroying cancerous and normal prostate cells. This timeframe seems to be variable in different patients, and, therefore, the PSA decline after radiation can vary considerably from patient to patient.118

Postradiation follow-up usually consists of obtaining a PSA level every three to six months for the first several years. If an individual’s PSA drops very quickly to extremely low levels (0.5 ng/mL) and stays there for several consecutive measurements, then the follow-ups are usually increased to every 6 to 12 months between measurements. If, on the other hand, the PSA is fluctuating or going down very slowly, additional PSA tests may remain at three months or may occur more frequently. Usually no other follow-up testing (bone scans, CT scans, MRIs, or another biopsy of the prostate) is done unless the PSA shows a significant rise after radiation treatment. For those who experience unusual or excessive side effects, the follow-up may be different. Such follow-up might entail examination of the rectum and colon for bleeding problems or examinations of the bladder or urethra for urinary problems.111

Normal prostate cells and cancerous prostate cells both produce PSA. Because of their long cell cycle time, it takes a while for both the cancer and normal cells to die, so PSA may be still be produced for some years. Also, there may be some residual normal cells remaining that result in PSA being detected in the blood. Several years after treatment with either seed implantation or external beam radiation, a patient’s PSA is expected to be

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 84 stable with very little fluctuation. The PSA does not necessarily have to be zero to indicate successful treatment. Again, this is because there may be some normal cells remaining, particularly after external beam radiation. These cells can produce a small amount of PSA. So, it is the stability of the PSA that is the most important feature. Most patients get to a PSA that’s below 1.0 ng/mL, but many achieve PSAs lower than 0.5 ng/mL, and some below 0.2 ng/mL.104,116,122

Although complications can and do occur, the vast majority of patients tolerate external beam radiation quite well.

Brachytherapy

Prostate seed implantation is a form of radiation treatment in which radioactive materials are placed directly into a cancer-affected organ with the intent of destroying the malignancy. The prostate receives a high dose of radiation to fight cancer while the bladder, rectum, and bowel receive very little radiation. The first transrectal ultrasound and template-guided prostate brachytherapy procedure was performed in Seattle, Washington, by two physicians, John Blasko and Haakon Ragde, in 1985. Today the procedure is successfully performed in hundreds of centers throughout the world.

The procedure is typically performed as a three-part process. The first is the planning phase, in which the patient’s prostate is carefully measured by ultrasonography. That information is then subjected to computer analysis to determine the appropriate number of seeds, seed strength (measured in millicuries), and the geometry of seed arrangement within the prostate. This planning process may be done a few weeks prior to the procedure or it may be performed in the operating room in conjunction with the actual seed insertion.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 85 The second part of the procedure is the seed insertion into the prostate. This requires an anesthetic of some type and is usually performed in either a hospital operating room or an outpatient surgery center. Needles are inserted through the skin between the legs (the perineum) and into the prostate under the guidance of real time imaging from an ultrasound probe, which has been placed into the patient’s rectum. A customized plan is made for each patient. The number, strength, and location of seeds depend upon the shape and size of the patient’s prostate and the dose prescribed by the radiation oncologist.123

Most of the time patients do not need to remain overnight in the hospital and can go home immediately following the implant. It is this convenience of treatment and rapid return to everyday activities that make seed implants very appealing. The final step after the implant procedure is a CT scan of the prostate and the seeds to determine that all the seeds are in proper position. This scan occurs anywhere from a day to a month after the patient goes home.

The modern method of prostate brachytherapy is yielding excellent results in controlling cancer, as evidenced by a 2001 study published in the International Journal of Radiation, , Biology, Physics. This clinical investigation, led by the physicians at Seattle Prostate Institute, showed that 87 percent of 125 patients with early stage cancer (prostate specific antigen [PSA] less than 10 ng/mL, Gleason score 2–6, T1–T2b) who received iodine- 125 seeds as their sole form of treatment showed no evidence of disease at 10 years. What’s more, the vast majority of patients achieved a PSA of 0.2 ng/mL. According to the study, with seed implants, a patient’s PSA usually declines to 0.2 ng/mL or less. Thus this study revealed that with seed implants a high percentage of patients can expect to be cured 10 years or

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 86 more after treatment. However, it may take seven or eight years for the PSA to reach 0.2 ng/mL or lower.121

As far as actual cancer recurrence, only 3 percent of patients had cancer recur in the prostate and another 3 percent had prostate cancer recur in another part of the body. The remaining 4 percent who were considered failures only had rises in PSA - no actual cancer could be discovered by testing. At the time of publication, no patients in this study who received prostate brachytherapy had died of prostate cancer.

There is one other intriguing aspect to the above-mentioned study. This group of men, who were all treated between 1988 and 1990, had a much higher rate of progression-free survival compared to a similar group of patients treated in 1986 and 1987. The conclusion is that physicians greatly improved their brachytherapy techniques after 1987, which has resulted in even better long-term, progression-free survival. It is probable that further refinements in technique that have been adopted since this study means that today’s outcomes are likely to be even better.124

Procedure

Prior to the procedure, the patient will receive an epidural. An epidural or spinal anesthesia blocks all sensation below the waist but patients may be given the option to remain fully awake and alert during the implant. Most men, though, prefer to have additional mild sedation. Patients who receive general anesthesia will be unconscious.

In most centers, a radiation oncologist and an urologist perform the implant together. Each physician contributes specific skills to the procedure. Others in the operating room include operating room nurses, a nurse anesthetist

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 87 and/or anesthesiologist, and someone from the physics team to track seed placement during the procedure and perform radiation surveys afterward. A radiation survey takes measurements of the amount of emitted radiation from the seeds that were just placed. This is usually done by use of a Geiger counter placed for a few seconds at the surface of the patient’s lower abdomen. The other purpose of a radiation survey is to check the used needles and bedding to be sure that no seed has inadvertently been left behind in the apparatus.125

A member of the physics team usually places the seeds into the needles just before the procedure. There are a couple of different ways to get the seeds in the needles. Loose seeds can be loaded one by one into the needle until the correct number is in each needle. Companies that manufacture the seeds also make seeds held together with a suture material that the body absorbs. All that has to be done is count the number of needed seeds, cut, and drop that strand into the needle. Increasingly, manufacturers are able to provide needles that have already been loaded with seeds according to the physician’s plan.

The loaded needles are inserted into holes in a radiation-shielded box that’s identically coded with letters and numbers matching the template that’s placed on the patient’s perineum. The template identically matches the grid coordinates of the dosimetry plan that’s derived from the ultrasound volume study. After anesthesia, the nurses carefully place the patient into a modified lithotomy position, meaning the patient is on his back with his thighs at a 90- degree angle to his body, thighs apart, and lower legs placed in stirrups. The perineum is carefully cleaned with an antimicrobial agent and this area may be shaved depending on the practice of each center. The urethra is also identified. There are a couple of different ways of doing this. Some centers

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 88 place a catheter into the urethra while others insert an aerated surgical jelly that shows up on the ultrasound.126

The team assembles a stabilization system to support the implant equipment. The physician introduces an ultrasound probe into the rectum (which the patient won’t feel due to the anesthesia), and then attaches that probe to the stabilization system. The final step is to attach a template grid to the stabilization system. This grid helps direct the needles through the perineum and into the correct locations within the prostate. The physician takes the needle from the needle box and inserts it into the corresponding template grid; and, verifies the needle position and depth by looking at an identical grid image on the ultrasound screen. The physician also takes precise measurements to double-check the needle position prior to releasing seeds.127

The entire procedure usually lasts from 30 minutes to two hours from the time the patient receives anesthesia until the implant is completed. Most implants require 16 to 30 needles and 60 to 130 seeds. Another way to implant the seeds is via a cartridge system, usually known as a MICK applicator. In this system, specially designed empty needles are placed through the template and into the patient’s prostate. When all of the needles are in the correct position, the MICK instrument is then attached to each of the needles in succession. The seeds have been loaded into cartridges, which are then fitted to the MICK instrument. By operating a plunger system, the seeds are deposited one at a time through the needle while another part of the apparatus retracts the needle at precise increments so that the seeds are accurately placed in the prostate from top to bottom.125

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 89 Both the preloaded needle and cartridge technique are acceptable and reflect the training and preference of the physician. Patients who ask to remain awake after receiving spinal or epidural anesthesia will be able to hear what’s going on. It’s unlikely, however, that they will be able to see the actual implant. Providers also encourage patients who remain awake to refrain from coughing, laughing, or boisterous conversation because these activities can be distracting or create unwanted movement of the prostate and/or misalignment of the template.

Each seed releases radiation within a confined area. All of the seeds contribute some amount of radiation to the overall implant. However, if some seeds are too far apart, then the dose between the seeds may be inadequate to fight the cancer. This inadvertent underdosing is called a “cold spot.” Skilled implant specialists will continually scan the length of the prostate with ultrasound during the procedure looking for areas devoid of seeds. If any develop, extra seeds are available to fill in these areas before the procedure is completed.128 A “hot spot” is just the opposite. Seeds that are too close together create an area in which the radiation dose is too high. A small hot spot is unlikely to cause any side effects. But a large hot spot could injure the urethra, the urinary sphincter, or the rectum. Fortunately, sizeable hot spots are rare with today’s preplanning methods.

The vast majority of brachytherapy patients have a very low risk of lymph node involvement. If the lymph nodes were to be sampled, this would be done via an open operation or laparoscopically at a time other than during the brachytherapy procedure.126 The physicians might look inside the patient’s bladder at the end of the implant with a cystoscope to make sure that no seeds strayed into the bladder. If there are blood clots or excessive bleeding, the bladder will be irrigated. The bladder will also be inspected to

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 90 make sure there are no bladder tumors. Some physicians avoid cystoscopies and instead use a catheter to flush out the bladder after the procedure in the event of blood clots or stray seeds. There is no preferred method.129

Most physicians prescribe antibiotics both before and after the implant. A few centers advocate the use of steroids prior to and for several days after the procedure to decrease swelling and prevent urinary blockage. Alternatively, some physicians use nonsteroidal anti-inflammatory medications such as ibuprofen. Alpha-blocker medications such as tamsulosin hydrochloride are very helpful in improving the strength of the urinary stream and are usually started before the procedure.125

There are two types of pain that patients may experience in the first day or two following seed implant. The first is an aching or tenderness between the legs where the needles were inserted. This is usually mild and only rarely requires pain medication. The second form of pain is a burning sensation when urinating. This pain is most severe the first several times the patient urinates following a seed implant. It then diminishes rapidly and usually does not last more than two or three days. Most patients are surprised at the lack of pain from this procedure; medications such as acetaminophen extra strength (ES) or ibuprofen are usually all that’s needed. Occasionally a patient will take a stronger pain medication for a few days. Men may see a small amount of blood or small blood clots in their urine for a day or two. This is to be expected.130

A few days later, a mild burning sensation may come back. It’s uncommon and usually mild. It comes from the radiation doing its job of killing the cancer and decreases as the radiation wears off. It often lasts between three and six months, though a few patients report they’ve had this symptom for

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 91 up to a year. In a few cases, the radiation may cause serious discomfort. The best thing patients can do to minimize the burning is to drink plenty of water and take the prescribed medications. Water will dilute the urine to make it more comfortable as it passes through the urethra.125

Patients will typically receive a few prescriptions after the implant, including one for an antibiotic and one for an alpha-blocker. Alpha-blockers relax the bladder neck so that it’s easier to urinate. The majority of patients use alpha-blockers for a few months. Some patients, however, require maintenance alpha-blockers for periods greater than one year. The medical team may also advise patients to take an over-the-counter anti- inflammatory medication such as ibuprofen for a short time. As an alternative, some doctors prescribe a new class of anti-inflammatory medications called COX-2 inhibitors such as rofecoxib and celecoxib, particularly in patients already on blood thinners such as warfarin.131

At anytime from the day of the implant to 30 days afterward, a CT scan or MRI of the prostate is performed to make sure the prostate is receiving the proper amount of radiation. If there is a significant cold spot, the medical provider will contact the patient to discuss options, including the possibility of having a second implant to put in a few additional seeds or undergo supplemental external beam radiation. Fortunately, this is rare. Also, a chest x-ray may be done to see if any seeds have migrated to the lung.132

In some patients, a seed will accidentally be deposited into one of the many veins that surround the prostate. The blood can carry the seed to a lung, where it can lodge and develop a two- to three- millimeter scar. There is no evidence to suggest that seed migration is harmful. If this migration does occur, it’s usually in the first four weeks after the implant. There have been

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 92 no reports of problems from migrated seeds and certainly the seed does not have to be removed. Nevertheless, if the patient is concerned about seed migration he can request seeds that are connected with absorbable suture material; these migrate less frequently.126

Post-Procedure

It is typically recommended that patients avoid all activities that apply pressure between the legs for the first month or two after the implant. If patients are doing well with few urinary symptoms after one month, they might try to go for a short bicycle ride or horseback ride of about 10 or 15 minutes. They would then wait 24 hours to see whether this short period of activity has worsened their urination or not. If patients notice that their urinary stream is thinner and less forceful, they should continue to avoid these activities for an additional month and then try it again. However, if there is no adverse effect on urination, they are probably ready to resume these activities.126

The radiation emitted by the seeds does not cause any part of a patient’s body or any of the bodily fluids to become radioactive. The radiation is of such low energy that almost all of it has dissipated before it even reaches the patient’s skin. Sensitive radiation detectors can pick up minute amounts of radiation that are emitted from the body. It should be noted that a physics document should be prepared for patients who travel, since most airports and some train stations are equipped with radiation detectors.133 Men don’t need to take special precautions with their spouses; sleeping in the same bed is fine. One study measured the dose of radiation received by the wives of 59 seed patients during a one-year period. The average dose was equivalent to taking a round-trip airline flight between New York and Tokyo.132

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 93 As soon as a man feels able, he may resume sexual intercourse. Occasionally, patients pass seeds with ejaculation. This is why some centers suggest patients should wear a condom or masturbate for the first three to five ejaculations. Initial ejaculations may be uncomfortable, and the fluid could be dark brown, black, or red. This is normal and comes from bleeding that occurred during the implant.127

Prostatic swelling, irritation, and discomfort may reduce erectile function right after the procedure. If the patient is still experiencing erectile dysfunction after the immediate side effects wear off (usually two to three months), the usual first step is a prescription of Viagra. There is increasing evidence that to maintain erections, frequency of erections is important so that’s why men are encouraged to get at least three erections per week. If the patient is able to be sexually active with the help of Viagra following implant, in time he may recover the ability to achieve erections and no longer need the drug. Viagra is effective in about 80 percent of patients who have erectile dysfunction from external beam radiation or seed implant.134

It is recommended that the patient take a few extra measures if he is around growing children or pregnant women after the implant. It’s fine to be in the same room, and if the patient keeps a distance of six feet they will get no more radiation than they would normally get from the environment (this is called background radiation). If the patient is closer than six feet, they will receive a dose of radiation that is slightly higher than background. To be extra safe, children should not sit on the patient’s lap for two months following an iodine seed implant and for three weeks following an implant of palladium seeds.129

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 94 Considerations135

 The prostate sits behind the pubic arch, which is the V shape created where the pubic bones meet. The pubic arch study is simply a rectal ultrasound or a CT scan done to evaluate the size of the arch and its relationship to the prostate.

 A narrow pubic arch can block the implant needles from properly entering the correct targets within the gland. The radiation oncologist looks at each slice of the prostate and draws the area to be treated, which may include an extra margin of tissue in some areas around the gland.

The radiation oncologist gives the physics team these images along with a prescription for how much radiation is needed. The physics team figures out where to place the seeds to create a cloud of radiation in and around the prostate gland while minimizing exposure to the bladder, urethra, and rectum. When the physics team is satisfied with this plan, they send it back to the radiation oncologist for final review and approval.

 Prostates can shrink anywhere from 30 percent to 50 percent with three to six months of hormone therapy. The larger the gland, the longer the need for pre-implant hormonal therapy. Most prostates will shrink sufficiently with hormones, unless the gland is massively enlarged (such as being much greater than 100 cc).

 Being relaxed during the volume study and pubic arch evaluation is important because the images from this ultrasound must be accurate; they are needed to plan the number and position of the seeds. Usually

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 95 a careful discussion and explanation by the person doing the ultrasound will calm the patient. A light sedative may be used to minimize the jitters, but the sedative can take hours to wear off and the patient will need someone to drive him home.

 Mapping the prostate means using a series of images to outline the prostate. Mapping involves inserting the ultrasound probe into the rectum and then taking images of the prostate every five millimeters, from the base to the apex. This usually takes from 15 to 30 minutes.

 Most centers pre-plan the procedure several weeks before the implant. Some medical providers, however, prefer to do the mapping and the physics work in the operating room. This is called real-time dosimetry or intra-operative planning. Although some providers claim superiority of one method over another, there is no current evidence to indicate one planning method is better than another.

 Both palladium and iodine give off very low-energy x-rays that only travel a short distance. This means that the dose of radiation delivered by both sources is confined to the prostate and the tissue immediately surrounding the gland.

 The primary difference between the seeds is the rate at which the radiation is released. The palladium isotope gives up its energy faster than the iodine isotope. With palladium, the prostate receives the radiation dose much quicker so the side effects come on earlier than with iodine — and they may be slightly more intense. But they also tend to go away faster than iodine’s side effects. The radiation from palladium does not travel quite as far as it does with iodine, which

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 96 may result in a lower dose to surrounding organs, but it may also mean more cold spots within the implant if the implant is not done accurately. There is no evidence that one type of seed is more effective for cure than another.

 Half-life is a physics term that means the time it takes for the isotope to release half of its radioactivity. The half-life for palladium-103 is 17 days. The half-life for iodine-125 is 60 days. Generally, the seed implant is considered active for five half-lives. If the half-life for palladium-103 is 17 days, and it takes five half-lives for the seeds to release the bulk of their radiation, the seeds will be radioactive for 85 days. For an iodine-125 implant, the active life of the seeds is about 300 days.

 The physical seed is permanent but the radioactivity is not. The seeds are actually titanium tubes into which the radioactive material is placed. Titanium is used because the body does not reject it; titanium is the same material used for joint replacements, such as hips. Because the body does not treat titanium as a foreign substance, there is no danger from these inert seeds remaining in the body after the radiation disperses. Titanium is not magnetic, so if the patient has to have an MRI after a seed implant, it is perfectly safe to do so.

 While a comparatively infrequent side effect after brachytherapy, it nevertheless happens in about 10 percent of cases. It occurs due to the radiation’s irritating effects on the urethra and prostate and resultant swelling of the prostate. Inserting a catheter for a few days or even a few weeks will treat this. After a week of having a catheter in place, a voiding trial will be performed to see if the catheter is still

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 97 needed. On rare occasions, a catheter may be necessary for several months. It’s important not to allow a physician to perform a TURP to relieve urinary retention while the seeds are still active, because the retention will usually resolve on its own.

High Dose Rate Brachytherapy

High-dose rate prostate brachytherapy (HDR) is almost always combined with external beam radiation to treat early and locally advanced cancer. There is some experimental work using HDR alone, but the results are currently unknown. The HDR procedure requires an inpatient hospital stay for a couple of days. Under ultrasound guidance and using a template similar to what’s used in permanent seed implants, small catheters are placed through the perineum and into the prostate. Next, a computer-controlled device inserts a high activity iridium seed into each catheter.

The treatment takes several minutes. Two or three treatments are given during a 24-hour period, and then the catheters are removed. No radioactive material remains in the prostate. Similar to seeds, this technology allows for the delivery of higher radiation doses than can be delivered with external beam radiation. However, the radiation from HDR is not higher than the doses from permanent seeds. Although the early results of HDR with external beam radiation are encouraging, this method of treating prostate cancer has not been as thoroughly studied as permanent seeds or external beam radiation.136

In terms of treatment considerations, it’s a little more difficult to undergo an HDR implant than a seed implant. This is because patients need to be in the hospital for two or three days with the needles and catheters in the prostate. But because radioactive material is removed from the prostate after only a

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 98 few days, patients have a shorter duration of the temporary urinary side effects of frequency, urgency, and a slow urinary stream.137

Eligibility

Most patients who are good candidates for radical prostatectomy are also candidates for seed therapy alone. However, the prostate gland must not be too large (it should be less than 60 grams or 60 cc). Ideally, the best candidates for seed monotherapy are patients with a PSA less than 10, Gleason score of 6 or less, and a DRE that does not suggest the tumor has extended outside the prostate. Because patients with significant urinary problems from BPH may have even more severe urinary problems after a seed implant, they may be better served with external beam radiation or radical prostatectomy.130

A patient with intermediate- or high-risk disease may be a candidate for implant alone, but it’s usually recommended that he get external beam radiation and seeds together. A PSA that’s higher than 10 ng/mL but less than 20 ng/mL may be considered for an implant alone if there is only a small percentage of cancer in the biopsy cores, or if the patient’s provider cannot feel any significant lumps or hardness during a DRE and based on the Gleason score. Some patients with a Gleason 7, a PSA less than 10 ng/mL, and only one or two positive biopsy cores can also be treated with seeds alone.

For very young men who have a life expectancy of more than 20 years, there may be a hesitation for recommending seed implants. There is a rare possibility that a patient might develop a different, radiation-induced cancer in the bladder or rectum. Radiation-induced cancers are extremely rare and take 15 to 30 years to develop, but this could be an issue for men in their

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 99 40s or early 50s. Whether existing urinary problems affect a patient’s candidacy for implantation depends on the type and severity of urinary problems. As men age, most develop some symptoms of BPH but these symptoms would not be a hindrance to implantation as long as the symptoms are not severe.

A common tool to evaluate the nature and severity of urinary symptoms is the American Urological Association Symptom Score Sheet. There are no fixed rules regarding the use of this test but in general, if the patient’s score is 10 or less he is less likely to have problems following seed implantation. If his score is between 10 and 19, he is usually still a candidate for seed implantation but may experience more in the way of urinary symptoms during the first few months following his implant. Patients who score more than 19 points should understand that they may have more severe symptoms. It is still possible to do seed implants in these cases, but other factors, such as prostate size and response to urinary medicines, need to be considered.132,136

The determination of whether a patient is a candidate for prostate brachytherapy from the standpoint of their existing urinary status may require additional testing, such as a flow rate test, post void residual determination, and cystoscopy by a urologist who is experienced and knowledgeable in seed implants.137

The question of cancer being outside of the gland can mean many different things. In the worst- case scenario, the cancer can spread from the prostate gland through the bloodstream to the bones. In this case, treatment of the prostate with seeds would not be appropriate. Prostate cancer can also spread by direct local extension, whereby small fingers of cancer may grow

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 100 through the capsule of the prostate and involve the surrounding fat, nerve bundles, or seminal vesicles. This extracapsular extension is divided into two groups: (1) focal or minimal and (2) extensive. Neither type of extracapsular extension can be accurately detected by CT scans, but the typical spread is only a couple of millimeters. This spread can be easily addressed by the seed implant since radiation implants are designed to reach outside the prostate an average of five millimeters or more.136

Fortunately, the incidence of seminal vesicle involvement is low and falling year by year. The lowermost portions of the seminal vesicles always receive radiation from the seeds. But seeds alone cannot treat the entire seminal vesicles. If the whole seminal vesicle needs to be treated, then external beam radiation therapy must be added. If a biopsy of the seminal vesicles is positive or other scans such as CT or MRI show unequivocally that the seminal vesicles are cancerous, external beam radiation alone is generally selected in these cases. Several institutions are treating patients with limited seminal vesicle involvement with hormones, external beam radiation, and seed implantation with seeding of the lower portion of the seminal vesicles.132

Patients who have had transurethral resection of the prostate (TURP) may be eligible for seeding. Eligibility for a TURP patient really depends on how much tissue was removed. TURPs conducted 15 to 20 years ago was often extensive, leaving only a small amount of prostate tissue. The early experience of seed implantation in TURP patients resulted in a high rate of incontinence, up to 35 percent. However, these early patients also received higher doses of radiation to the TURP defect than is delivered with current brachytherapy techniques.130

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 101 Today, TURP patients are treated with more seeds placed into the periphery of the gland and less in the center (this is called a peripheral loading pattern). This approach significantly lowers the dose to the TURP area, thereby reducing the risk of incontinence to 5 percent to 10 percent. Therefore, TURP patients can be successfully implanted if they have good urinary continence and the prostate volume study shows that a good deal of prostate tissue remains.138

Advantages

The most important advantage is that the cure rates are excellent. No other type of radiation is capable of delivering a higher dose to the prostate, which is reassuring for getting rid of the cancer. In terms of convenience, it’s a one-time, minimally invasive procedure that requires less than one hour of spinal, epidural, or general anesthesia. Recovery times are short and patients can generally return to their normal routines within a few days. Although temporary urinary side effects are expected for a few months, the vast majority of patients have no long-term problems with urination or bowel function.

Disadvantages

One of the main disadvantages of prostate brachytherapy is that most patients temporarily experience moderate to severe urinary urgency and frequency, and a weak urinary stream for several months, especially at night. These urinary side effects are more pronounced than what patients experience with external beam radiation. In addition, a small proportion of men will find that they are unable to urinate at some stage over the first few weeks after the procedure. If this is the case, a catheter may be required.138

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 102 Another disadvantage of both prostate brachytherapy and external beam radiation is that there has not been an opportunity for surgical staging. Testing the lymph nodes and performing a microscopic examination of the tissues surrounding the prostate can allow more details to be learned of a patient’s cancer status. These additional tests can give a clearer picture of the extent of the patient’s disease, supplementing the prognostic information gleaned from the patient’s Gleason score and PSA. With today’s early detection, cancer spread to the lymph nodes is rare.139

Still one more disadvantage is that following prostate brachytherapy, the PSA sometimes takes many years to achieve a nadir (the lowest point). Achieving a nadir provides reassurance that the cancer is in remission. In addition, the PSA can fluctuate in the first two or three years due to the “PSA bounce” phenomenon. Patients must tolerate this uncertainty for several years following brachytherapy.140

Post- Implant Effects

Post Implant effects are broken into two categories: side effects and complications. Side effects are temporary and expected. They occur because of the action of the treatment. For instance, one side effect of seeding is frequent urination, which lasts for a few months while the swelling of the prostate that occurs during the procedure and the radiation is active. This usually resolves by itself after the swelling goes down and the radiation dissipates.

Complications can have a couple of different meanings. The first connotation is an adverse event that is permanent — such as frequent urination that does not go away after the radiation has dissipated. Another general definition is a problem that occurs for the first time quite a while after the

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 103 procedure. An example would be rectal bleeding, which can begin a year or more after the implant procedure.136

Urinary Side Effects

It’s almost universal that patients will experience urinary side effects for a while after seeding. These side effects are usually frequent urination, a sense of urgency, and a slower and weaker urinary stream. They are most prominent in the first few months and gradually resolve as the swelling after the implant subsides and the seeds’ radiation decays.141

There are two phases of irritation that may result in urinary urgency. The initial sense of needing to urinate arises just after the procedure. It’s due to swelling and irritation to the prostate from the needles being inserted into the gland and the catheter. In some instances, the cystoscope inserted through the urethra and into the bladder for a quick double-check of the bladder after the procedure can cause swelling. This irritation takes about a week or two to diminish and then things are improved for a short time. However, shortly after the symptoms subside, the urinary urgency begins anew; this time, from the radiation. The peak time for this urgency is during the strongest release of radiation, which is usually from two to six weeks after the implant. Patients may have to plan their activities around their urinations during this time, so they are not caught with an urgent need to urinate and no way to relieve themselves.139

Radiation treatment also causes a number of reactions in the prostate, urethra, and lower portion of the bladder, which may take several months to resolve even after the radiation is gone. For this reason, many patients experience some degree of side effects after a seed implant that may extend out to a year or more. Most patients find that their urinary function recovers

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 104 completely and is as good as it was before the seed implant. It’s widely accepted that between 5 percent and 15 percent of patients might need a catheter or other treatment for urinary retention after implant. The usual number most physicians quote when a patient asks this question is 10 percent.129

Some foods and liquids can irritate the bladder and prostate, causing increased urgency, frequency, discomfort, and a slower stream. The most offending foods are alcohol, citrus foods (including vitamin C), caffeinated beverages (especially coffee), and hot, spicy foods.133 Food and beverages that may cause bladder irritation are outlined below.

Foods likely to be bladder irritants in many or most people:  Alcoholic beverages  Apple juice  Apples  Cantaloupes  Carbonated beverages  Chilies/spicy food  Chocolate  Citrus fruits and drinks  Coffee, including decaf  Cranberries and cranberry juice  Grapes and grape juice  Guava  Peaches  Pineapple  Plums  Strawberries

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 105  Tea  Tomatoes  Vinegar  Vitamin B complex  Vitamin C

Foods That May Cause Bladder Irritation:

 Avocados  Bananas  Brewer’s yeast  Canned figs  Champagne  Cheese (aged)  Chicken livers  Corned beef  Fava beans  Lima beans  Mayonnaise  Nutrasweet  Nuts  Onions  Pickled herring  Prunes  Raisins  Rye bread  Saccharine  Sour cream  Soy sauce  Wine

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 106  Yogurt

Substitutions:  Low-acid fruits: Pears, apricots, papayas, watermelon  For coffee drinkers: KAVA (low-acid instant), Pero  For tea drinkers: Noncitrus herbal tea or sun-brewed tea  Vitamin C: Buffered ascorbic acid  Dietary substitutions: Small amounts of cooked or raw green onions are allowed, processed cheese (American, cottage, cream cheese, and ricotta), carob or white chocolate instead of chocolate, homegrown low-acid tomatoes, imitation sour cream, pine nuts, and freezer jams and jellies that don’t require lemon juice to set the pectin.

Incontinence is rare following seed implants. The fact is that older men are more likely than younger men to experience incontinence — regardless of whether they are being treated for prostate cancer. By some definitions, 5 percent of men (age 70) are incontinent prior to receiving treatment. Therefore, elderly men with preexisting urinary symptoms will probably have more problems with incontinence after any prostate cancer treatment, including seed implant.136

It’s common for an older man to experience a strong urine stream during the day and a weaker one at night. Upon lying down at night, fluids pool in the central body and stretch blood vessels in the chest. This stretching sends signals to the body to make more urine, which subsequently increases the frequency of nighttime urination. Also at night, the involuntary nervous system (the autonomic system) can slightly inhibit the bladder from completely emptying. When the patient attempts to urinate, his stream may be slower and there could be a feeling of not being quite done. This

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 107 incomplete emptying causes the bladder to refill more quickly and the patient may feel the need to continue trying to urinate, sometimes several times.126

Alpha-blocker medications such as tamsulosin hydrochloride, terazosin hydrochloride, and doxazosin mesylate help counteract these problems by helping the urethra to relax, which allows for more complete emptying. In addition, patients should refrain from drinking any beverages for approximately three to four hours before going to bed. When watching television or engaging in other quiet evening activities, it’s a good idea for the patient to keep his feet elevated. This will help the fluids that have collected in the lower extremities work their way back up and be urinated out of the body before retiring. It’s also recommended that the patient attempt to empty his bladder completely before going to bed. Taking a warm shower in the night may help the flow, and walking around prior to urination can sometimes improve the stream.

A small percentage of patients are permanently left with a bit more sensitive bladder. They experience a need to get up more often at night to urinate, more difficulty postponing urination when the urge occurs and a weaker urinary stream. One of the benefits of seed implants is that the specific problem of leaking urine is very rare. Stress incontinence, which is weakness of the pelvic muscles that causes leakage with coughing, straining, or exercise, is also exceedingly rare after seeds.132,136

The second type of incontinence is known as urge incontinence. With this form of incontinence, patients who experience extreme urgency find that they tend to leak a bit of urine if they can’t find a bathroom in time. After

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 108 seed implantation, patients may experience this type of incontinence for the first few weeks, or even months, but it usually goes away.132

Kegel exercises strengthen the muscles that help to keep the urethra closed, thus improving incontinence and urine control. Incontinence isn’t as much of a problem with seeds as it is with surgery, but many medical providers think it’s a good idea to practice Kegel exercises if the patient is experiencing any degree of incontinence.142

The concern about performing any surgical procedure in the prostate or urethra following seeding is that the radiation may cause some scarring, making it more difficult for any surgical trauma to heal. Because of this, it is recommended that surgery be avoided unless absolutely necessary; the longer the patient can wait to have this kind of surgery following a seed implant, the better. However, some patients need some type of procedure to open up their prostate if they’ve had troublesome, persistent blockage symptoms that medication fails to relieve. Following the principle of doing the least amount of surgery possible, a transurethral incision of the prostate (TUIP) is often recommended. This is less traumatic than a TURP and can often relieve the obstruction. A TURP can be performed after seeds, but it’s recommended that only a small amount of tissue be removed, which is often called a “mini- TURP.”143

A patient should wait at least six to nine months after brachytherapy before undergoing a TUIP or mini- TURP. This time period allows the radiation to dissipate and the tissue to heal. Frequently, the urinary side effects resolve on their own. Following seed implantation, the prostate will gradually become smaller over a period of several years. There is no evidence that the

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 109 prostate regrows later, and patients followed as long as 15 years after their implant have not noted any re-enlargement of their prostate.132

Some patients with BPH have greatly enlarged prostates but few urinary symptoms. Conversely, there are men whose BPH has caused only a little bit of prostate enlargement yet they have striking urinary difficulties. Thus, there’s not always a correlation between the size of the patient’s enlarged prostate and the amount of trouble he may have. Similarly, there’s no way to predict whether the BPH symptoms will improve after seeding. Simply stated, some patients who have BPH-related symptoms improve over the years after an implant, while others do not. We can’t foresee who those will be.

Occasionally, burning and increased urinary frequency develop one to three years after brachytherapy. This can be due to a small stricture (scar tissue) that may develop in the urethra. If this occurs, cystoscopy — an outpatient procedure to widen (dilate) the urethra — is usually effective in treating this problem.127

Bowel Side Effects

Because a very small portion of the rectum receives radiation, it’s rare for patients to experience any rectal or bowel side effects from a seed implant alone. Some patients, however, notice that their bowel movements are more irregular and frequent for a few weeks following the implant. This effect usually disappears rapidly. Up to 15 percent of patients will have minor rectal bleeding either seen on the toilet tissue or with the stool. Typically, it doesn’t hurt, the amount of bleeding is usually insignificant, and it usually resolves on its own. Occasionally, it will require a prescription for a suppository or another minor treatment. On rare occasions, a seed patient

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 110 may report a burning sensation during defecation, which can be treated with medication.

Patients who receive external beam radiation with seed implants have a slightly greater chance of temporary rectal or bowel side effects. These side effects tend to come on a bit later. This group of patients also shows a greater incidence of developing more permanent bowel problems or a tendency for diarrhea. With the advent of intensity modulated radiation therapy (IMRT), there is less bowel or rectal toxicity during and after treatment.

There are some brachytherapy patients (although it’s a much smaller percentage than external beam patients) who develop some blood in their stools about a year or two after the implant. This is usually caused by some slight fragility to the lining of the rectum. Any rectal bleeding that occurs months after the implant needs to be reported to the doctor immediately. The physician will probably recommend that colonoscopy be performed to rule out anything serious. Most of the time, this bleeding will resolve on its own.99

It is advised that any procedure to the rectum after brachytherapy be conservative. Simple prescription suppositories that help accelerate the body’s normal healing process should be the first-line treatment. It is recommended that implant patients do not undergo electrocautery because it might create an ulceration or fistula. Likewise, performing a biopsy on an area of radiation proctitis can result in a fistula or ulcer that does not heal. The patient is advised to talk with his brachytherapist before undergoing any invasive procedure to deal with minor rectal bleeding after brachytherapy.144

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 111 Sexual Function

Radiation affects the seminal vesicles producing prostatic fluid, which may cause some patients to experience a significant reduction in the ejaculate. Also, as the normal cells die, the prostate becomes smaller, shrinking to about half its normal size. When the medical provider performs a digital rectal exam (DRE) after the implant, he or she will notice that over time the prostate comes to feel small and flat.98

The radiation effect on both cancerous and noncancerous cells is subtle and takes a long time. Although noncancerous prostate cells are damaged immediately when radiation is given, the cells can continue to live for many months or even years. For the cells to die from the radiation damage, it requires them to attempt to divide into two cells. Prostate cancer cells and noncancerous prostate cells divide at their own rate so it can take a long time before full shrinkage of the prostate is seen. It’s been observed that in some patients, it took up to five years for most of the normal prostate to disappear following the radiation treatment. This is an indication of how slowly radiation works and that it takes time for the prostate to shrink to its smallest size. Not all prostates will shrink radically. The amount and rate of prostate shrinkage has no bearing on controlling the cancer.145

There’s controversy and debate about what exactly causes erectile dysfunction after brachytherapy. It has been speculated that it could be due to radiation’s effect on the nearby nerves or the effect on the blood vessels that supply an erection. A recent study shows that one year after the implant, 90 percent of men who had good erectile function prior to the procedure maintained erectile function. About half of these patients reported some decrease in the erection’s firmness or durability but were still able to penetrate with the help of Viagra.102

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 112 Long-term effects on erectile function occur over a period of years. After five years, 50 percent of brachytherapy patients maintain the same erectile function as they had before seeds. In addition, these brachytherapy patients are, on average, 10 to 15 years older than patients that undergo nerve- sparing prostatectomy, as reported in the medical literature. It’s recognized that men who have other medical problems that tend to affect their blood vessel system will have weaker erections. These are conditions such as diabetes, arteriosclerosis, and a history of heavy smoking. Older men are more likely to have these medical problems, and if they do, they are more susceptible to erectile dysfunction following treatment. Lastly, many prescription medications cause erectile dysfunction.95

The penis length can appear to shrink after radical prostatectomy. This has to do with cutting out the part of the urethra that runs through the prostate; shortening the urethra can shorten the penis. A few patients who had either external beam radiation or brachytherapy have also reported a shortening of their penis. It’s not clearly understood why this occurs. Since many men have fewer erections after cancer treatment, this has been speculated to be the cause of penile shrinkage.102

Following radical prostatectomy, patients can climax but they do not ejaculate since the surgery removes both the prostate and the seminal vesicles. Following brachytherapy, the amount of the ejaculate is often diminished. The small amount of ejaculate is thought to come from the distal portions of the seminal vesicles, which are not implanted. About 5 percent to 10 percent of men have completely “dry ejaculations” after brachytherapy, and most have significantly reduced volume. Approximately 5 percent of patients have no change in ejaculate volume. A small number of patients report discomfort, particularly with the first few ejaculations. The reason for

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 113 the pain is probably due to swelling or some slight scarring of the ejaculatory ducts. This pain usually subsides with subsequent ejaculations.146

Although it is thought the testicles can continue to produce sperm after the seed implant, there is a remote possibility that the radiation will affect these sperm. It is recommended that attempts to impregnate be avoided for at least eighteen months. However, since the nature and quality of the ejaculate is dramatically altered by the seed radiation, it is unlikely that a patient would be fertile. This, however, is not a guarantee - on occasion, men are still fertile following this procedure. In fact, some radiation oncologists have had patients who successfully fathered healthy children after their prostate seed implant.147

PSA Level after Implant

The patient’s PSA levels can actually increase immediately after the implant as anything that irritates the prostate (trauma, infection, cancer, or inflammation) will temporarily increase the PSA level. How often the PSA should be checked after implant varies between medical providers and may depend somewhat on how the PSA acts following therapy. In general, providers like to see a PSA test repeated every three to six months until the PSA reaches a low, stable level. The surgical standard for PSA is 0.2 ng/mL. It may take years for the PSA to reach its lowest level after radiation. In one case, it took seven years for a patient’s PSA to drop to 0.2 ng/mL.31 Rather than a strict rule about the PSA needing to decline to a specific and relatively arbitrary level, there is another well- accepted standard used by brachytherapists, urologists, and radiation oncologists to monitor what’s happening after the implant. When the PSA falls to a low level after brachytherapy and stays put for successive readings (barring the PSA

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 114 bounce phenomena, which will be discussed later) the patient is considered disease- free (or progression- free) by PSA criteria.

A low PSA level does not automatically indicate the presence of prostate cancer. It could simply reflect the fact that the few remaining normal prostate cells continue to produce PSA. A small amount of PSA may be seen not only after implant, but after surgery or external beam radiation as well. While PSA levels would be expected to decrease to a level of less than 1.0 ng/mL, the absolute level is not as important as the trend over time. Prostate specific antigen levels should slowly decline over several years and then stabilize. There is no set standard for an absolute PSA value because every man is different. One patient’s PSA could be 0.5 ng/mL, while the patient sitting next to him in the waiting room could have a PSA of 0.7 ng/mL, and yet another patient could have a PSA of 0.2 ng/mL. The important factor for each of these men is that his PSA has reached its lowest point and is not rising.53

It’s not unheard of for a small number of brachytherapy patients to have stable PSA levels above 1 ng/mL. In general, however, the lower the PSA, the better. Long-term studies have demonstrated that patients whose lowest PSA is less than 1 ng/mL have more than a 90 percent chance of being free of prostate cancer 10 years after implantation.

Approximately 24 percent to 40 percent of patients will experience a PSA bounce (also referred to as a spike or blip), which means the PSA temporarily goes up and then declines. This usually occurs between 12 and 36 months after implant. The magnitude of this rise can be a few tenths of a point or several points. The PSA of one patient rose to 13 ng/mL and then dropped right back down. Approximately one-quarter of these bounce

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 115 patients will have a second PSA bounce from a few months to a few years after the first PSA bounce.46

Researchers have not yet been able to ascertain what causes the PSA bounce. It may be due to normal cells that are dying and releasing their PSA, inflammation, or a mild infection. Because the PSA bounce may be due to an infection or swelling, the physician might prescribe antibiotics or an anti-inflammatory medication. If the patient’s PSA is up during a routine follow-up visit, the normal course of action would be for the provider to repeat the PSA in two to three months. While many bounces are of short duration, some last many months, during which time the PSA is carefully monitored.148

Interestingly, medical providers have noted that more frequently it’s younger men who have PSA bounces and their bounces are higher. Perhaps it’s because they have more normal, healthy prostate cells and when their larger number of cells die, they produce a bigger, temporary PSA bounce. That could explain why a man in his forties may experience a PSA bounce that’s much higher than a man in his 70s. There are two other things seed implant patients need to know about PSA fluctuations. The PSA test results can vary according to the laboratory performing them. Therefore, it’s wise for a patient to ask his provider to make sure to send each PSA test to the same lab. Ejaculation can also temporarily increase a man’s PSA level, which is why sexual activity should be avoided for two days prior to any PSA test.174

There really is no need to perform post-implant prostate biopsies within two years of the procedure. Biopsies in the first couple of years are likely to be inaccurate because many cells are biologically alive but reproductively dead

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 116 — the cancerous cells look alive under a microscope but they are incapable of reproducing. If the PSA begins to rise after approximately two years, the provider will assess whether to conduct a biopsy. Biopsies are most often performed to determine if the recurrent cancer is local (within the prostate).99

If the PSA rise is rapid, a biopsy may not be ordered. This is due to the fact that a rapidly rising PSA is a signal that the patient may have distant spread (prostate cancer that has migrated to some other site in the body). Taking out the prostate won’t cure this cancer. In these cases, hormones would be the usual next step. Another circumstance in which a biopsy might not be ordered when the PSA starts to rise after seeding is when the patient is elderly. Salvage therapy — a second treatment such as surgery or cryosurgery — to deal with a local recurrence can take an extra physical toll on older patients. That’s why patients of advanced age and/or in poor health are often better candidates for hormonal therapy in this kind of situation.35

Cryosurgery/Cryotherapy

Prostate cryosurgery relies on rapid freezing and thawing to destroy cancer cells. This procedure is also called cryotherapy and cryoablation (ablation is defined as destroying the function of a tissue). Unlike a radical prostatectomy, which is the complete removal of the prostate, cryosurgery destroys the prostate and a rim of surrounding tissue while the gland is still in the body.149

After the patient receives anesthesia, the surgeon inserts a device into the bladder and urethra to prevent them from freezing. Next, the surgeon places an ultrasound probe in the rectum. This helps guide the placement of several cryo probes through the perineum and into the prostate. Extremely cold gas,

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 117 either argon or nitrogen, circulates through the probes. The gas causes the tips of the probe to become extremely cold and freeze the prostate tissue. In some centers, the prostate thaws for about 30 minutes before the surgeon applies a second treatment. Early studies indicate that this second round may do a more thorough job of killing larger amounts of tissue.177

The patient is able to go home the same day and his catheter is left in place for some time. The reports of pain are minimal, and doctors begin monitoring the PSA level beginning at six months.150 Although advances in the technique have reduced the rates of incontinence over the past few years, erectile dysfunction (ED) continues to be a problem. The procedure freezes the neurovascular bundles that control erection, which means a high level of ED in patients who undergo cryosurgery. Additionally, a concern is that studies show more than 17 percent of patients has prostate cancers that involve the urethra and more than 34 percent of patients have cancer within a few millimeters of the urethra. The urethra is warmed during cryosurgery, and warming the urethra might allow cancer cells near the urethra to survive. Other serious injuries to the bladder and rectum can also occur. There is no evidence yet that this treatment is superior to surgery or radiation therapy.152

Hormone Therapy

Most testosterone comes from the testicles. The adrenal glands make a small amount of testosterone as well as other male hormones. These other hormones are called adrenal androgens. The term androgen is used to describe the entire group of male hormones. The aim of hormonal therapy is to reduce the amount of testosterone and androgens in the bloodstream, depriving many prostate cancer cells of the fuel they need to grow. Once the male hormones are withdrawn, one of three things will happen to a prostate

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 118 cancer cell; it will undergo spontaneous death (called apoptosis), remain alive but not grow, or it might continue growing. Cells in this last category are called androgen-independent prostate cancer cells because they don’t need androgens to grow. Reducing testosterone usually lowers the prostate specific antigen (PSA), shrinks the prostate, shrinks the tumor, or stops the progress of the disease — frequently for many years. Generally speaking, however, hormone therapy alone does not cure prostate cancer.153

There are four primary ways to interfere with testosterone: 1) surgically removing the testicles (orchiectomy), 2) using drugs to interrupt testosterone production (luteinizing hormone-releasing hormone [LHRH] agonists ketoconazole and aminoglutethimide), 3) using drugs that block androgen action (antiandrogens), and 4) taking estrogen.

Surgery to Reduce Testesterone

Orchiectomy:

Surgical removal of the testicles (orchiectomy) was for many years the only way to reduce testosterone. It’s used less frequently today, though, because of the availability of hormonal therapy medications. When orchiectomy is done, it’s usually an outpatient procedure. The surgeon makes a small incision into the scrotum and removes the testicles. Immediately, testosterone declines to a very low level called the castrate range. (The scrotum remains, and if the patient opted for reconstructive surgery prior to undergoing orchiectomy, the surgeon inserts prostheses shaped like testicles). The advantage of orchiectomy is that it’s a very economical way to reduce testosterone. There is no need for the patient to receive regular doses of hormone-blocking medications. The disadvantage is that the operation is irreversible.154

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 119 Drugs That Interrupt Testosterone Production

 LHRH agonists:

Testosterone production begins in the hypothalamus, which is a portion of the brain controlling numerous bodily functions. The pituitary gland sits directly beneath the hypothalamus. When the testosterone level in the blood falls below a certain threshold, the hypothalamus sends LHRH to the pituitary gland. The pituitary then sends another set of chemical signals to the testicles. The testicles go to work and produce testosterone. The group of drugs known as LHRH agonists breaks this cycle at the very beginning by turning off the hypothalamus’s production of LHRH.

The most frequently used LHRH agonists are given as injections and last between one and four months. After the injection, it takes about three weeks for the testosterone to fall to the castrate range. The primary advantage of these drugs is that the testosterone reduction is temporary, so stopping the drug means most of the side effects will probably disappear. In some men, because of an initial increase in testosterone after the first injection, the medical provider will add a second oral antiandrogen medication for several weeks to block this effect.

 Prevention of androgen production:

There is another group of drugs that prevent the testicles from making testosterone and the adrenal glands from making androgens. These drugs include ketoconazole and aminoglutethimide. These drugs are not usually used as first-line hormonal therapy treatment but are more commonly used to treat hormone refractory prostate cancer (this is

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 120 when prostate cancer no longer responds to other types of hormonal therapy). These drugs are often used as second-line hormonal therapy before undertaking chemotherapy.

Drugs That Prevent Androgen Action

 Antiandrogens

Inside prostate cancer cells are structures called androgen receptors. Androgens in the bloodstream bind to these receptors and when they do, it’s like flipping a switch that causes the cancer cells to grow. Antiandrogen drugs increase androgen levels in the bloodstream. But, they also plug into the receptors so that androgens in the bloodstream cannot. With antiandrogens blocking the receptors, the male hormones are unable to turn on the switch.

In some cases, some practitioners treat low- and intermediate-risk patients with early prostate cancer solely with antiandrogens. For younger patients especially, this approach may reduce the risk of erectile dysfunction. Though there may be some quality of life benefits to using antiandrogens alone, this approach requires further study. (For high-risk patients, however, antiandrogen monotherapy is usually not recommended). Antiandrogens can, and often are, used in combination with LHRH agonists. The very first dose of LHRH agonist causes a brief, sharp increase in testosterone before the testosterone drops to castrate levels. Such a rapid increase in testosterone can cause a painful tumor flare if there’s cancer in the bone. Since the antiandrogen plugs up the androgen receptors, it helps prevent this flare.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 121 There are a few names for the dual treatment with LHRH agonists and antiandrogens — combined hormonal therapy, total androgen blockade, or complete hormonal blockade. Men on total androgen blockade tend to experience more side effects than those taking a single hormonal agent.

 Estrogen

Estrogen is a hormone that can interfere with testosterone production. For years, higher doses of diethylstilbestrol (DES) — a synthetic form of estrogen — were used to treat prostate cancer as an alternative to orchiectomy. These doses are not recommended today because of the availability of the LHRH agonists. At higher doses, DES increases the chance of developing serious heart disease or blood clots. Lower doses are often used to treat hormone-refractory prostate cancer. One advantage to DES is that it is effective and very inexpensive. There are also other estrogen-containing pills or patches.155

Use of Hormone Therapy

In the past, hormone therapy was used only in cases of metastatic cancer. This is because orchiectomy — an irreversible operation — was the best way to control testosterone levels. But with LHRH agonists and antiandrogen drugs — whose effect is reversible — hormonal therapy is no longer just for men with metastatic prostate cancer. That’s why if the patient has other stages of prostate cancer his provider might recommend hormonal therapy along with radiation or surgery.156

Occasionally men with early stage prostate cancer will be treated solely with hormones. Although hormones can control prostate cancer for many years, hormonal therapy by itself generally does not cure it. Because hormones nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 122 have so many side effects and there are other excellent curative treatments, it’s uncommon to give hormones alone to early stage patients. When it’s used alone for early prostate cancer, it’s usually for elderly patients who cannot tolerate conventional treatments such as surgery, seed implantation, or external beam radiation.

When prostate cancer is confined to the organ, survival rates tend to be better than when there is a positive surgical margin or extracapsular extension. Since hormonal therapy shrinks cancer cells, the idea is to shrink the tumor so that it is completely inside the prostate. Unfortunately, hormonal therapy for three to eight months before surgery has not resulted in improved outcomes. The question of whether the patient will have hormones in the case of positive margins probably boils down to where he receives treatment.

Medical providers at some centers advocate no treatment unless the margins are strongly positive. In this case, a common treatment is radiation therapy. On the other hand, some doctors argue that even if the margins are not strongly positive, the patient still needs aggressive therapy, including hormones and radiation. But this is not yet proven to be superior to radiation alone. There are many factors to consider in the case of positive margins: the extent of the positive margins, whether the cancer extended into the seminal vesicles, the Gleason score, the PSA level before and after surgery, and the patient’s willingness to undergo more treatment. Because there are so many factors, turning to the provider for counsel and advice is very important.153

Hormones can be used before, during, and after external beam radiation therapy. The idea behind using hormones before radiation is that the

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 123 hormones may kill some cancer cells and weaken others, making them even more susceptible to the radiation. Large randomized studies show that hormone therapy before and during moderate dose radiation has significant benefits for local control and disease-free survival for locally advanced cancer. Thus, the standard of care for patients with locally advanced cancer is to combine hormone therapy and external beam radiation.

In this setting of locally advanced prostate cancer, some studies suggest that using hormones for several years is better than using them for a short time. Therefore, in treating locally advanced prostate cancer, many providers recommend continuing hormone therapy for several years after the completion of external beam radiation therapy. However, one landmark study recently showed that two months of hormones before whole pelvic plus prostate radiation and two months during radiation therapy was effective in patients with a risk of lymph node involvement of over 15 percent and a pre-treatment PSA of under 100. So, the optimal duration of hormone use and how best to combine it in patients with locally advanced disease is still being debated. For men getting radiation for early cancer, however, there is no convincing evidence that adding hormones is helpful or necessary. Clinical trials evaluating this question are currently ongoing.

Hormones may be used before seed implants to help shrink a prostate that’s too large. Physicians will commonly recommend three to six months of hormones to a man with an overly large prostate in order to shrink it to a more ideal size for the implant. A few months of total androgen blockade will shrink most prostates by about 40 percent. In terms of using hormones to increase the effectiveness of implants, several studies have been published looking at the impact of a short course of hormone therapy (three to six

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 124 months) combined with brachytherapy. None of these studies has shown there’s a benefit in adding a few months of hormones to a seed implant.157

Many medical providers would recommend two to three years of hormone therapy if the dual treatment of seeds and external beam radiation therapy is used for early stage, high-risk disease (high Gleason score or a high PSA). If a patient received a different treatment prior, and is experiencing a rise in PSA, the determination to begin hormone treatment will depend on a number of factors. Men in this situation often live for many years without the cancer spreading to the bones or other organs. But other patients develop cancer spread in a much shorter timeframe. While there’s no sure way to predict which patient will have rapid spread, how fast the PSA doubles is an indicator. A rapid PSA doubling time (10 to 12 months) is more likely to be associated with a poorer outcome than a PSA doubling time of greater than one year (other factors include original PSA, stage, and Gleason score).134

Many men with rising PSA want treatments that will lower the PSA under any circumstance. Moreover, some data suggest that early hormonal intervention after failed treatment, while the disease is minimal, may extend survival— but these data remain controversial. There are many clinical trials that do not include hormonal therapy, and some men choose a non-hormonal approach first and delay the use of hormonal therapy. Patients with rapid PSA doubling times should consider treatment, while those with a slower PSA doubling time can possibly delay any therapy.158

Intermittent Hormonal Therapy

Intermittent Hormonal Therapy involves simply stopping and then re-starting hormonal therapy. It’s hypothesized that this on-again, off-again use of hormones delays the development of hormone-refractory prostate cancer,

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 125 but this concept is not proven. The general idea is that hormones are stopped after a given number of months of therapy or when the PSA reaches a very low level. After the hormonal therapy is stopped, the PSA is expected to rise. When the PSA rises to a certain level again, the drugs are restarted. A potential advantage of intermittent therapy is that the side effects may go away or diminish during the time off the androgen suppression. Intermittent therapy is controversial, and clinical trials looking at its effectiveness are now underway.159

Side Effects

Medical providers commonly warn patients about loss of sex drive (libido) and the subsequent erectile dysfunction, and hot flashes.

 Loss of libido:

Losing the desire for sex is common with orchiectomy or LHRH agonists. Only a small percentage of patients maintain their normal sexual desire. It’s impossible, though, for us to predict who will retain libido. The loss of sexual desire often results in the loss of spontaneous erections.

 Hot flashes:

A hot flash is a sudden rush of warmth to the face, neck, upper chest, and back. It lasts for a few seconds or up to an hour. They range from mild to severe. The frequency and severity are different for every man, and hot flashes can occur one or many times each day. The good news is that prescription medications can alleviate hot flashes, as may dietary additives such as soy.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 126  Breast enlargement:

Some patients, particularly those on long-term hormonal therapy, may experience enlargement of the male breast tissue (called gynecomastia). This can occur with antiandrogens or LHRH analog treatments alone or in combination. Radiation is proven to be very effective at preventing or decreasing the severity of the gynecomastia if given before high-dose bicalutamide or DES.

Radiation to prevent gynecomastia before LHRH analog therapy has not been studied and is not routinely performed. Although radiation can prevent breast enlargement, it does not prevent breast tenderness. Prescription drugs can be very effective in treating tender breasts. If gynecomastia is severe or extremely bothersome, surgery or liposuction is an option. Radiation to the breast tissue will not treat gynecomastia once it has occurred.

 Weight gain:

When on hormonal therapy, men gain an average of five to twelve pounds. There is a loss of muscle mass with an increase in total body fat, most of which accumulates in the trunk. Reversing the weight gain isn’t easy, but patients can — and should — make a point of increasing their exercise and moderating their caloric intake. A proactive approach will help minimize this problem.

 Testicle changes:

Hormonal therapy can result in a reduction in the size of the testicles. On intermittent therapy, when the hormonal therapy is stopped, the testicles may regain some, but usually not all, of their original size.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 127  Loss of bone mineral density:

In one recent report, men on combined hormonal therapy of an LHRH agonist and an antiandrogen lost 4.7 percent of bone in their lower spine and 2.7 percent from their hips (this compares with the normal loss of 0.5 percent to 1 percent per year). This level of bone loss is actually greater than what post menopausal women experience. Some men already have osteoporosis before starting hormonal therapy and they could be treated with a type of drug called a bisphosphonate to help increase bone density.

Patients should have a DEXA (dual x-ray absorptiometry) scan to assess whether you have normal bone density before you start hormonal therapy. If a patient has normal bone density, some of the best things he can do to counteract bone loss are to exercise and take calcium and vitamin D supplements.

 Anemia:

Anemia, which is a low level of red blood cells, is frequently reported as a side effect of hormonal therapy. Most patients have some anemia, but only about 10 to 15 percent develop symptoms due to a low red blood count. Drugs can be used to treat anemia during hormonal therapy. Red blood cell production resumes at more normal rates once the androgen suppression is stopped.

 Lipid changes and aggravation of existing diseases:

Hormonal therapy tends to increase total cholesterol and the level of low-density lipoprotein (LDL) — the so-called “bad” cholesterol. Lipid levels should be monitored and if the situation warrants, the patient’s

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 128 provider can prescribe cholesterol-lowering drugs. If hypertension (high blood pressure) and/or diabetes exist, hormonal therapy can aggravate these two conditions, although the exact mechanisms of why this happens remain unclear.

 Other changes:

Some patients report side effect such as fatigue or lack of energy. As with some of the other side effects brought about by hormone therapy, there is no good explanation for why this happens. It is known that regular exercise, and particularly resistance exercises (free weights, weight machines, elastic tubing, calisthenics), can improve symptoms of fatigue and overall quality of life. This type of exercise should be done initially under the supervision of a physical therapist or licensed personal trainer. When hormone therapy is stopped, this fatigue usually goes away. Some patients are also more depressed and more moody. Again, regular exercise helps relieve this anxiety. In more severe cases, providers can prescribe an antidepressant.

Chemotherapy

Hormonal therapy controls prostate cancer by depriving the cells of testosterone and other androgens. At some point, though, hormonal therapy may no longer be effective because some of the cancer cells were not originally responsive to hormones or they later became resistant to hormone treatment. If the patient has been on hormone treatments, the PSA may not necessarily tell the whole story. In other words, a person on hormonal treatment for a long time could be diagnosed with bone metastases and still have a low PSA. In any event, when hormonal treatments are no longer effective, it’s time to consider chemotherapy.160

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 129 Chemotherapy is used most often when hormonal treatments have failed and the cancer cells no longer respond to hormones. In recent years, it’s been used earlier in patients to prevent the advancement of disease. Despite the fact that chemotherapy has not yet been shown to extend life expectancy in prostate cancer patients, many patients have had dramatic responses to chemotherapy and some individuals have definitely had their lives extended with chemotherapy.161

Chemotherapy is injected directly into a vein or swallowed as a pill. The patient then goes into a short recovery period for a few days or weeks, and then receives another dose. The duration of treatment varies, depending on the drugs. Sometimes the medications are used alone, sometimes in combination. A few of the more common chemotherapy drugs used in prostate cancer are docetaxel, doxorubicin, estramustine phosphate, etoposide, mitoxantrone, paclitaxel, and vinblastine. The combination of mitoxantrone and prednisone is often used in patients with hormone- resistant prostate cancer who are also in pain. The taxanes (docetaxel or paclitaxel) are used alone or in combination with estramustine or other agents such as calcitriol.

Chemotherapy drugs kill cells as they divide, and fast-growing cancer cells are more susceptible to these drugs than normal cells. Some other fast- growing cells — hair follicles, the lining of the gastrointestinal tract, and bone marrow — may also be temporarily affected by the chemotherapy. Although these noncancerous cells may be damaged by the therapy, the body will restore them after the chemotherapy is stopped. Specific side effects will depend on the type, amount, and duration of the drugs. Medication can control some of the side effects, including nausea and vomiting.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 130 The most commonly reported temporary side effects include:162

 Bleeding or bruising from minor injuries  Diarrhea  Fatigue related to anemia  Hair loss  Loss of appetite  Mouth sores  Nausea and vomiting  Risk of infection

Bone-directed Treatment

Strontium-89 and samarium-153 are isotopes that emit a short, low-dose radiation and can be used to alleviate bone pain. A radiation oncologist or diagnostic radiologist injects these isotopes into a vein. They concentrate in those areas of the bone that contain cancer and deliver the radiation dose exactly where it is needed. This results in cancer cell death, decreases bone pain, and lessens the need for medications. The response rate is about 80 percent and the side effects are minimal. It can delay the appearance of other painful bone metastases.163

One of the most useful treatments to relieve bone pain is external beam radiation. A short course of radiation, usually about two to four weeks to the specific area of pain, can bring about dramatic relief and strengthen the bone, prevent fracture, and prevent or treat spinal cord injury. This can be very important to preserve a high quality of life and keep patients independent and at home.164

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 131 Investigational Therapies

New drugs and treatments to fight prostate cancer are under constant development. Here’s a brief rundown of some of the more promising investigational treatments.

 Immune Therapy:

Several treatments are now being explored to see whether the body’s own immune system can fight prostate cancer.  Dendritic cells — which are from the immune system — are taken from the patient’s blood, treated in the lab to generate a response to fight prostate cancer, and injected back into the patient.

 Anti-CTLA-4 is an antibody that stimulates T-cells, which are cells from the immune system that can fight prostate cancer.

 Vaccine trials examine whether specific substances elicit an immune response to kill prostate cancer cells.

Vaccine Trial Summary165 Aiming to increase treatment options for prostate cancer patients who have an early relapse, investigators from a multi-institutional cooperative group -- including Rutgers Cancer Institute of New Jersey -- have demonstrated that a vaccine therapy that stimulates the body's own immune defenses can be given safely and earlier in the course of prostate cancer progression.

As part of a Phase II clinical trial, adult patients with advanced prostate cancer (as evidenced by two rising prostate-specific antigen or PSA values and no visible metastasis) whose cancer is resistant to hormone therapy and had either surgery or radiation were recruited from member institutions in the ECOG-ACRIN Group. In their work, published in the current online edition of European , ECOG-ACRIN investigators examined two different experimental treatment options.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 132 In step one, patients were treated with PROSTVAC-V/TRICOM and PROSTVAC- F/TRICOM. PROSTVAC-V is derived from a vaccinia virus that was used for many years to vaccinate against smallpox. This virus is modified to produce a PSA protein that helps focus the body's immune response to the PSA in the prostate tumor. In addition, it is modified to produce three other proteins that help increase an immune cell's ability to destroy its target (TRICOM).

PROSTVAC-F is made from the fowlpox virus, which is found in birds and not known to cause any human disease. It contains the same genetic material as PROSTAC-V, but is given multiple times to further boost the body's immune system.

Patients in the study were given one cycle of PROSTVAC-V/TRICOM followed by PROSTVAC-F/TRICOM for subsequent cycles in combination with a drug known as GM-CSF. GM-CSF is a protein normally made by the body to increase the amount of certain white blood cells and make them more active. When in drug form, it is used to boost the body's immune system to fight off disease. After six months from first treatment, 25 of 40 eligible patients (63 percent) were found to have no disease progression and experienced minimal toxicity. Median pre-treatment PSA velocity was 0.13 log (PSA)/month as compared to median post-registration (six months) velocity of 0.09 log (PSA)/month, which represents an improvement in PSA doubling time from 5.3 months to 7.7 months. The second part of the study included the addition of hormone therapy (androgen ablation) to the PROSTVAC-VF/TRICOM combination. In the 27 patients eligible for this step, 20 patients (74 percent) experienced a complete response at seven months.

"Previous studies by the ECOG-ACRIN Cancer Research Group and others have shown it is optimal to explore agents like PROSTVAC that harness the body's own defenses in shutting down cancer. With our current findings demonstrating the safe use of combination vaccine therapy earlier in the course of prostate cancer progression, we are laying the groundwork for future immunotherapy options for this patient population," says Cancer Institute of New Jersey Director Robert S. DiPaola, MD, who is the lead author on the publication. Dr. DiPaola and colleagues note that while this research is supportive of larger federally funded studies, the small number of patients and the absence of a control group limit this study.

There are also investigations into drugs that block growth factors — these are the proteins that cause tumor cells to divide and grow. Current studies are also examining whether drugs that impede the tumor’s ability to generate a network of blood vessels will kill the tumor. It’s thought that starving the tumor will stop it from growing. These are only a few of the many new therapies under development, with many more on the horizon.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 133 Dietary and Lifestyle Recommendations

There a number of things a patient can do once diagnosed to slow the growth of early stage prostate cancer. Reducing the amount of saturated fat in the diet appears to be one of the best ways to impact prostate cancer. Substantially cutting down on saturated fat — dairy fat, the fat in red meats, and other animal fats — could slow the growth of the prostate cancer tumor. In a recent study, researchers carefully reviewed the diets of more than 425 prostate cancer patients. Their conclusion was that the number one factor from these patients’ diets that favorably influenced prognosis was reducing saturated fat intake.166

No one is exactly sure why reducing saturated fat is beneficial in fighting cancer, but it could be that the structure of saturated fat “feeds” tumor growth. It is recommended that saturated fat make up less than 10 percent of the patient’s daily calorie intake. Please note that it doesn’t do any good to cut out excess amounts of saturated fat only to replace all of those calories with sugar. Prostate cancer seems to like a high caloric intake. Medical providers are now seeing higher rates of prostate cancer in obese men. Obesity is also a problem because it not only increases the risk of being diagnosed with prostate cancer in the first place, but it can worsen the prognosis.

There’s some disagreement about whether physical activity reduces the risk of prostate cancer, but there are definitely some favorable studies indicating exercise helps overall prostate health. The best part about exercise is that there is little downside. Physical activity will benefit both mental and overall physical health. For those reasons alone, it makes sense for prostate cancer patients to incorporate more activity into their lives. It doesn’t matter what the patient does — walking, swimming, jogging, rowing, or other activities.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 134 It is most important that the patient moves his body regularly, and exercise enough to maintain a healthy body weight. In some individuals this means 30 minutes per day about three times a week, but in others it could mean 30 minutes per day seven days a week.

In the countries that have a low risk of prostate cancer, foods with a high source of naturally occurring plant estrogens — such as soy — are regularly incorporated into the diet. Providers recommend making soy a regular part of the diet, giving it as much priority as increasing fruits and vegetables and decreasing saturated fat. Soy is one of the only foods approved by the FDA that is allowed to advertise that it lowers the risk of heart disease.167

Flaxseed is a good source of a type of plant estrogen called lignans. In fact, flaxseed is the most concentrated source of lignans. Researchers at Duke University had men with prostate cancer use several servings of flaxseed daily and reduce their daily fat intake before they had their prostates removed. In one month, the average cholesterol level dropped by 27 points and the subjects’ PSA levels also decreased. The researchers found enough changes in the cancer cells to suggest that a fat-restricted diet supplemented with flaxseed may affect the biology of prostate cancer. It’s too early to make a definite claim, but researchers say such findings warrant more study into this dietary approach.

There is one minor drawback to the use of flaxseed. Flaxseed is quite high in fiber. If patients take it at the same time that they take other medications, it reduces the absorption of those prescription medicines. So, patients will need to be sure to take flaxseed, even flaxseed oil, at a different time than they take prescription medications. Also, moderation is a good rule. One or two servings a day of flaxseed are all that is needed. In addition, it is

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 135 important to remember that most cancer and cardiovascular studies have focused on the flaxseed itself, not the oil or the pills.168

Supplements and Treatment Considerations

For patients on external beam radiation or seed implantation, it is recommended that they avoid all dietary supplements during the therapy and for several months afterward. One of the ways radiation works is to create free radicals that destroy prostate cancer cells. Because some high- dose antioxidant pills are designed to destroy free radicals, they might interfere with radiation therapy. Once the radiation is complete or the radioactive prostate seeds have spent their energy, then it’s reasonable to resume these supplements. This should usually take three to six months (depending on the half-life of the seed implant being used). During this time, it’s a good idea to focus more on lifestyle changes (regular exercise, weight loss or maintenance, and a good diet).169

Osteoporosis is bone loss or a weakening of the bones. While women are more prone to osteoporosis as they age, some men also experience it. Furthermore, when men are on hormonal therapy, they may show an accelerated loss of bone. That’s why it’s important for men who are on long- term hormonal therapy (more than four months) to talk with their providers about taking vitamin D and calcium supplements to help promote bone growth.170 The precise dosage of calcium and vitamin D will vary, depending on bone loss experienced before, during, or after treatment. Patients should consult with their providers about getting an osteoporosis screening test. After this is complete, the provider will assess the results and determine if there is a need for possible supplements and/or drug treatments for osteoporosis prevention.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 136 These osteoporosis supplements appear to decrease the risk of colon cancer in high-risk patients, help prevent fractures, and aid in cardiovascular health. A cardiovascular trial showed that patients who took calcium supplements for a year increased their good cholesterol by 7 percent. Interestingly, the countries that have the lowest rates of cardiovascular disease and prostate cancer also have the lowest rates of bone fracture.

Summary

This course provided a general overview of current concepts, diagnostic advances, and novel therapeutic approaches to the management of prostate cancer. It is widely reported that prostate cancer is the most common malignancy diagnosed in men in the United States. The current lifetime risk of developing prostate cancer is 17%, with an estimated lifetime cancer specific mortality risk of 3%. The diagnosis of prostate cancer rapidly increased in the mid-1980s, with the advent of the serological biomarker prostate specific antigen (PSA) which has played a pivotal role in the screening and early detection of prostate cancer worldwide.

Prostate cancer is the most commonly diagnosed non–skin cancer in men in the U.S., with a lifetime risk for diagnosis currently estimated at 15.9%. Most cases of prostate cancer have a good prognosis even without treatment, but some cases are aggressive; the lifetime risk for dying of prostate cancer is 2.8%. Prostate cancer is rare before age 50 years, and very few men die of prostate cancer before age 60 years. Seventy percent of deaths due to prostate cancer occur after age 75 years.

Although prostate cancer is the most prevalent cancer amongst men after skin cancer, it is also one with a very high rate of successful treatment and recovery. It also tends to be one of the slowest growing types of cancer.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 137 Over two million men in the U.S. count themselves as prostate cancer survivors, and this number continues to grow. However, it is important to understand that there is not yet a 100% cure rate for prostate cancer, and that it can be fatal even with treatment, so medical professionals need to be aware of the symptoms, stages, and various treatments to ensure the best possible outcome for their patients.

From what was almost uniformly a poor prognostic malignancy associated with highly morbid therapies, prostate cancer has emerged as a potentially curable disease, with state of the art diagnostic and therapeutic approaches. Advancements in the last 30 years have redefined the surgical approach of localized prostate cancer with minimally invasive surgical approaches for the most part being the primary treatment approach.

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nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 138 1. Prostate cancer typically develops in the ______zone of the prostate.

a. transition b. central c. anterior d. peripheral

2. The ______is primarily comprised of muscle tissue.

a. anterior zone b. vas deferens c. central zone d. seminal vesicles

3. Lack of vegetables in the diet (especially broccoli-family vegetables) is linked to

a. slow-growing tumors. b. low-risk prostate cancer. c. higher risk of aggressive prostate cancer. d. genetic factors related to prostate cancer.

4. True or False: Body mass index, a measure of obesity, IS linked to being diagnosed with prostate cancer.

a. True b. False

5. In most instances, when physicians discuss prostate cancer, they’re referring to

a. urothelial cell carcinoma. b. bladder cancer. c. sarcoma. d. adenocarcinoma.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 139 6. Which of the following is NOT a risk factor for prostate cancer?

a. Tall height b. High calcium intake c. Alcohol consumption d. African-American race

7. True or False: If prostate cancer cells begin to grow in the bones, it is still considered prostate cancer, not bone cancer.

a. True b. False

8. Prostate cancer can spread in several ways but it usually spreads first through the

a. lymphatic vessels around the prostate. b. lymph nodes in the pelvis. c. capsule of the prostate. d. seminal vesicles.

9. Enlargement of the prostate in Benign Prostatic Hyperplasia (BPH) squeezes the urethra, making it difficult and often painful for men to urinate because

a. BPH is a fast-growing tumor. b. the bladder is in close proximity to the prostate. c. the urethra runs through the central zone of the prostate. d. the urethra runs through the prostate.

10. Prostatitis is a/an ______the prostate.

a. infection in b. enlargement of c. of d. None of the above

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 140 11. A medical provider may predict a tumor’s speed of growth in prostate cancer by

a. watching how fast the PSA level is rising. b. a patient’s Gleason score. c. MRIs or bone scans. d. All of the above

12. One of the concerns raised about prostate-specific antigen (PSA) testing is

a. it has a low success rate. b. its over-diagnosis of prostate cancer. c. it does not diagnose aggressive prostate cancers. d. it does not detect bone cancer.

13. True or False: Over-diagnosis and overtreatment of prostate cancer means that many men will experience the adverse effects of diagnosis and treatment of a disease that would have remained asymptomatic throughout their lives.

a. True b. False

14. ______is a symptom specific to metastatic prostate cancer.

a. Urinary urgency b. Bone pain c. Decreased stream d. Hematuria

15. With respect to prostate-specific antigen (PSA) testing, the following is true:

a. it is proven to lower prostate cancer mortality rates. b. it is universally recommended by the medical establishment. c. it can lead to unnecessary biopsies. d. “normal” PSA levels are the same for men of all ages.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 141 16. Prostate-specific antigen-based screening that results in the detection of asymptomatic prostate cancer cases leads to

a. reduction of prostate cancer mortality. b. over-diagnosis of prostate cancer. c. discovery of aggressive tumors. d. fewer biopsies.

17. True or False: All contemporary recommendations for prostate cancer screening incorporate the measurement of serum PSA levels.

a. True b. False

18. The evidence from studies shows that the number of men who avoided dying of prostate cancer (after 10-14 years) because they were screened for the disease is

a. high. b. about 50%. c. very small. d. one in ten.

19. The consequence(s) of false-positive prostate-specific antigen (PSA) tests include(s)

a. hospitalization. b. more biopsies. c. psychological negatives (worrying about prostate cancer). d. All of the above.

20. U.S. Preventive Services Task Force recommends

a. raising the PSA threshold before ordering a biopsy. b. PSA screening should be done in all cases. c. employer-based PSA screening should be continued. d. that physicians should decide whether to do a PSA test.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 142 21. In most prostate cancer cases diagnosed today, the Digital Rectal Exam (DRE) may find

a. nonpalpable tumors. b. palpable tumors. c. cancer located in the vas deferens. d. cancer located in the transitional zone.

22. Noncancerous conditions may elevate prostate-specific antigen (PSA), such as

a. benign prostatic hyperplasia (BPH). b. prostate inflammation or trauma. c. prostate infection. d. All of the above

23. True or False: An elevated PSA does not necessarily indicate cancer: It only points to something that needs further investigation.

a. True b. False

24. The National Cancer Institute recommends that a patient with a PSA level ______should get a PSA test every other year.

a. less than 1.0 ng/mL b. lower than 4.0 ng/mL c. between 1.0 - 2.0 ng/mL d. above 2.0 ng/mL

25. The most recent information suggests that it may be reasonable to consider PSA levels of 2.5 or 3.0 ng/mL as

a. requiring a biopsy. b. normal. c. evidence of prostate cancer. d. above normal.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 143 26. Which of the following is true with respect to adjusting PSA levels based on a patient’s age?

a. PSA decreases as a man ages. b. PSA levels are the same regardless of age. c. adjusting PSA levels based on age is controversial. d. adjusting PSA levels based on age is widely accepted.

27. True or False: Most PSA (called “complexed PSA”) binds to other proteins in the blood; the remaining unattached PSA is termed “free PSA.”

a. True b. False

28. Men with a lower percentage of “free PSA” have a/an _____ risk for prostate cancer when compared to men with a higher percentage.

a. lower b. higher c. zero d. equal

29. True or False: PSA testing is scientifically proven to reduce the risk of dying from prostate cancer.

a. True b. False

30. If the patient has a large prostate, an elevated PSA level may be due to the presence of

a. prostate inflammation b. prostate cancer. c. more glandular tissue. d. All of the above

31. A urinalysis is the best test to evaluate an infection

a. of the central zone. b. of the prostate. c. of the bladder. d. vas deferens.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 144 32. Prostate-specific antigen (PSA) velocity measures the rate at which PSA

a. rises over time. b. is discharged through urination. c. is discharged during ejaculation. d. is expressed through the prostate.

33. If prostate cancer does not cause PSA to elevate, it may be that the tumor is

a. faster-growing and has lost the ability to produce PSA. b. in the central zone of the prostate. c. in the bladder. d. in the vas deferens.

34. Common side effects of a biopsy for prostate cancer is/are

a. a small amount of bleeding from the rectum. b. a small amount of blood in the urine. c. blood in the semen. d. All of the above

35. Prostate-specific antigen (PSA) levels that rise more than ______in a given year may suggest that further testing for prostate cancer is needed.

a. 4.25 ng/mL b. 2.00 ng/mL c. 0.75 ng/mL d. 1.00 ng/mL

36. To reduce the risk of bleeding, patients should avoid aspirin, anticoagulants, and nonsteroidal anti-inflammatory medications ______the biopsy.

a. the day of b. the week following c. a week prior to d. the day before and after

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 145 37. A pathologist looking at tissue samples from a prostate biopsy is looking for ______of these cells and glands.

a. changes in the shape and size b. the most common cell pattern c. the second most common cell pattern d. All of the above

38. The Gleason score for a patient assigns a number from one to five to the most common cell pattern seen, and to the second most common pattern, with 5 being

a. the least malignant. b. the most malignant. c. slow-growing tumors. d. benign tumors.

39. True or False: Higher Gleason scores mean that the prostate cancer is faster-growing and aggressive and will require more aggressive treatment.

a. True b. False

40. “Atypical hyperplasia” is an overgrowth of cells that are somewhat abnormal and

a. normal cells. b. do not have the characteristics of cancer. c. have the characteristics of cancer. d. indicates a higher risk for cancer.

41. Ploidy analysis examines

a. the DNA content of cells. b. perineural invasion of cells. c. prostatic intraepithelial neoplasia. d. the Gleason score.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 146 42. Transrectal Ultrasound helps

a. diagnose perineural invasion of cells. b. often to determine a cancer’s stage. c. detect prostate cancer. d. guide the biopsy needle.

43. The presence of cancer in an ultrasound is present as evidenced by

a. abnormal cells. b. hyperechoic (white) regions. c. hypoechoic (black) regions. d. almost any ultrasound pattern.

44. If a patient has a PSA less than 20 ng/mL and a Gleason score of 7 or less, the risk of detectable spread of cancer to the bone is

a. 10%. b. 50%. c. less than 1 percent. d. high.

45. A CT scan is useful to determine or show

a. enlarged pelvic lymph nodes. b. if lymph nodes are cancerous. c. the presence of bone cancer. d. All of the above

46. True or False: Endorectal MRIs are particularly useful in determining if cancer has spread outside the prostate.

a. True b. False

47. Stage is the determination of the ______of cancer.

a. grade b. type c. tumor growth-rate d. extent

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 147 48. When a physician conducting a digital rectal examination (“DRE”) can feel the tumor in not more than half of one side (one lobe) of the prostate the patient has

a. stage T2a disease. b. stage T1a disease. c. stage T1 disease. d. stage T3a disease.

49. The specific treatment used will depend on a number of factors, including the

a. severity of the cancer. b. patient’s age. c. patient’s overall health. d. All of the above

50. Androgen deprivation therapy (ADT) to treat prostate cancer is known as

a. brachytherapy. b. hormone therapy. c. palliative care. d. stereotactic radiation therapy.

51. The likely treatment for a patient who is diagnosed with low- grade, low-stage prostate cancer but who has suffered multiple heart attacks and has an unstable heart is

a. external beam radiation therapy. b. immediate surgery (prostatectomy). c. watchful waiting. d. the radical retropubic approach.

52. True or False: During radical retropubic surgery, the surgeon will immediately remove the prostate if cancer is detected in the pelvic lymph nodes.

a. True b. False

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 148 53. Decreased rates of urinary incontinence, erectile dysfunction (ED), and other side effects have resulted from

a. technical advances in radiation therapy. b. sural nerve graft. c. unilateral nerve-sparing surgery. d. bilateral nerve-sparing prostatectomy.

54. ______is a form of radiation treatment in which radioactive materials are placed directly into a cancer-affected organ with the intent of destroying the malignancy.

a. External beam radiation b. High-energy photon radiation c. Brachytherapy d. Pelvic radiotherapy

55. Which of the foods listed below is NOT likely to be a bladder irritant?

a. Pears b. Cantaloupe c. Coffee d. Cranberries

Correct Answers:

1. d 11. d 21. b 31. c 41. a 51. c 2. a 12. b 22. d 32. a 42. d 52. b 3. c 13. a 23. a 33. a 43. d 53. a 4. b 14. b 24. c 34. d 44. c 54. c 5. d 15. c 25. b 35. c 45. a 55. a 6. c 16. b 26. c 36. c 46. b 7. a 17. a 27. a 37. d 47. d 8. c 18. c 28. b 38. b 48. a 9. d 19. d 29. b 39. a 49. d 10. a 20. a 30. d 40. b 50. b

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 149 References Section

The reference section of in-text citations include published works intended as helpful material for further reading. Unpublished works and personal communications are not included in this section, although may appear within the study text.

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