Prostate Cancer: Screening and Management Dr. Lynnetta Faith Payne Board Certified Urological Surgeon Quiz 1. The most common site of prostate cancer in the prostate is the transition zone. T or F 2. Studies have shown that 70% of 70 year olds have prostate cancer. T or F 3. Most prostate cancers are hormone sensitive and respond favorably to androgen hormonal ablation the effect is long-lived. T or F 4. Anything that inflames the prostate can cause a rise in the PSA. T or F 5. Since the introduction of PSA as a screening tool in 1986, the number of total prostate cancer deaths has decreased by approximately 5%. T or F 6. The greatest benefit of screening appears to be in men ages 40-52 years. T or F 7. The PSA velocity is best determined by checking the PSA every 3 months for 1 yr. T or F 8. Prostate cancer was the first malignancy to be shown to be hormone dependent. T or F Case #1 July 13, 2013, a 59-year-old African American male presents with lower urinary tract symptoms, a of PSA 28 ng/ml, and an AUA symptom score of 24 Allergies: NKDA Medications: finasteride, 5 mg daily; terasozin, 10 mg daily; metformin; lisinopril Med: (+) HTN, NIDDM Surgical History: NONE FH: (+) Prostate cancer, HTN, DM Physical Exam: Prostate: 3+, no nodules August 15, 2013, he is referred to urology for TRUS of prostate, US-guided needle biopsy U/S: 43 gram prostate, mixed echogenicity Path: 10/14 cores (+), Gleason 4 + 5 August 24, 2013, CT: (+) (B) Iliac adenopathy, (+) obturator adenopathy to right, 1-1.6 cm(+) lesions to pelvis, sacrum, coccyx, L5 Bone scan: question of L4/5 involvement ECOG: 0 Treatment for Metastatic ACP Leuprolide, bicalutamide initiated September 20, 2013, PSA 0.85 Alkaline phosphatase 236, calcium 9.7 September 30, 2013, denosumab started for SRE prevention October 17, 2013, PSA 1.32, test <10; treatment options discussed November 14–December 19, 2013, 3 cycles of sipuleucel-T March 19, 2014: PSA 1.85, ALP 202 June 20, 2014: PSA 2.14, ALP 258, new onset back pain (right SIJ) requiring NSAID, occasional opiates Discussion Based on guidelines, this patient with asymptomatic, metastatic castration-resistant prostate cancer has several treatment options. This patient is a candidate for sipuleucel-T. Additionally, other options include abiraterone with prednisone, enzalutamide, and docetaxel. Objectives 1. Identify and name the basic anatomic zones of the prostate gland, including the locations where prostate cancer develops 2. Describe the physiologic role of the prostate – "what does the prostate do?" 3. Describe the distinctive epidemiological features of prostate cancer 4. Understand the controversy surrounding the use of serum PSA as a screening tool for prostate cancer. 5. List the signs & symptoms of prostate cancer 6. Describe the natural history and the common patterns of progression of prostate cancer 7. List the major components in the staging of prostate cancer 8. Briefly describe the treatment options for localized and metastatic prostate cancer 9. Describe when prostate cancer does NOT need to be treated 1. Identify and name the basic anatomic zones of the prostate gland, including the locations where prostate cancer develops The prostate is a male sex accessory gland located within the pelvis below the bladder and above the urogenital diaphragm. The prostate encircles the urethra like a doughnut and is derived from the urogenital sinus. There are 4 basic anatomic zones of the prostate: the anterior zone, the peripheral zone, the central zone, and the transition zone. The vast majority of prostatic carcinomas arise in the peripheral zone of the prostate, whereas benign prostatic hyperplasia (BPH) occurs in the transition zone. Peripheral Zone; the most common site of ACP The vast majority of prostatic carcinomas arise in the peripheral zone of the prostate, whereas benign prostatic hyperplasia (BPH) occurs in the transition zone. 2. Describe the physiologic role of the prostate – "what does the prostate do?" The role of the prostate is to secrete fluid into the ejaculate that accompanies sperm and seminal vesicle fluid to make up the semen. The contributions of the prostate to the ejaculate include; acid, zinc and a serine protease known as PSA (prostate specific antigen) that is an enzyme responsible for the liquefaction of semen. 2. Describe the physiologic role of the prostate – "what does the prostate do?" The prostate continues to grow (hyperplasia) with age and may cause voiding dysfunction. Prostate cancer is the most common solid organ cancer in men and is currently the second leading cause of cancer death in men after lung cancer. Bones, stop growing after puberty and muscle and fat cells also stop dividing. But cartilage – in ears and noses - continues to grow until the day you die. Likewise the prostate continues to grow with age. Cystoscopic image of BPH and bladder outlet obstruction. 3. Describe the distinctive epidemiological features of prostate cancer Studies suggest that this cancer is much more common than observed clinically and thus any screening strategy must take care not to diagnose cancer in patients that will not suffer clinically from the disease. Autopsy studies have shown about 70% of men deceased in their seventies have prostate cancer present. The incidence of clinically diagnosed prostate cancer and mortality is highest in Blacks, intermediate in Caucasians and least in Asians. Early detection is key Being derived from a sex accessory gland, most prostate cancers are hormone sensitive and respond favorably to androgen hormonal ablation BUT the effect is short-lived due to either the development of or selection for hormone insensitive clones within the malignancy. Thus, the treatment stratagem for prostate cancer today is early detection whilst the tumor is confined to the prostate or surrounding tissues and can be cured by either removal or treatments aimed at the primary. Metastatic Prostate Cancer Although there are low response rates to currently available chemotherapies and immunotherapies and a palliative effect of hormonal therapy, there are no cures for metastatic prostate cancer. Traditionally, androgen deprivation therapy (ADT) has been the standard initial treatment for metastatic hormone-sensitive prostate cancer (mHSPC), with chemotherapy utilized in the castration-resistant setting. Clinical Trials (Chaarted and Stampede) The CHAARTED study showed a 13.6-month survival improvement and the STAMPEDE study showed a 10-month survival improvement with ADT plus docetaxel, compared with ADT alone, in the hormone-sensitive setting. Mitoxantrone, docetaxel, and cabazitaxel are three chemotherapeutic agents currently approved for the treatment of metastatic prostate cancer, after castration resistance has developed. Trials Chemotherapy has also been evaluated in the neoadjuvant and adjuvant settings for high-risk localized prostate cancer. Numerous neoadjuvant trials evaluating docetaxel or paclitaxel, alone or in combination with hormone therapy prior to radical prostatectomy, have shown a low rate of pathologic complete responses and mixed toxicity profiles. So again I will say there are low response rates to currently available chemotherapies and immunotherapies and a palliative effect of hormonal therapy, there are no cures for metastatic prostate cancer. SCREEN! Objectives 4. Understand the controversy surrounding the use of serum PSA as a screening tool for prostate cancer. 5. List the signs & symptoms of prostate cancer 6. Describe the natural history and the common patterns of progression of prostate cancer 7. List the major components in the staging of prostate cancer 8. Briefly describe the treatment options for localized and metastatic prostate cancer 9. Describe when prostate cancer does NOT need to be treated PROSTATE CANCER SCREENING While there are no symptoms with early stages of prostate cancer; early detection, including PSA screening, has played a part in decreasing prostate cancer mortality. The serum PSA test and the digital rectal exam are complimentary tests that, along with other key variables including patient ethnicity, age and family history, should serve as a strategic fund of knowledge to be used when deciding whether or not to proceed with biopsy. PSA A flawless and standardized interpretation of elevated PSA values has yet to be determined. Although it has been well demonstrated that patients with elevated serum PSA levels are more likely to be harboring aggressive disease, elevated PSA levels can also be seen in less biologically aggressive prostate cancers. Causes of elevated PSA Adenocarcinoma of the prostate Benign prostatic hypertrophy Infection Urogenital tract instrumentation (i.e. catheter placement) Anything that can cause inflammation within the prostate gland. Over diagnosis Serum PSA screening interpreted outside the context of important patient-specific variables carries with it a significant risk of what has been called over diagnosis. The identification and treatment of patients who might otherwise have lived out the rest of their lives without experiencing any of the terrible symptoms associated with advanced prostate cancer. Since the treatment of prostate cancer is associated with a significant level of patient morbidity (including bowel dysfunction, urinary dysfunction, and impotence), the use of serum PSA as a screening tool has been a topic of significant controversy. United States Preventative Services Task Force (USPSTF) In May 2012, a