Primary Care Update: Cervical Cancer

Continuing Medical Education Primary Care Update: Cervical Cancer

1.5 AMA PRA Category 1 Credits™, including 1.5 hours Ethics/Professional Responsibility

A Case-Based Discussion Salvatore J. LoCoco, MD, FACOG Original release date: July 1, 2010 Expiration date: July 1, 2013 Providing Oncology Education for Primary Care Physicians History pain management, tobacco cessation, ovarian cancer, late effects of cancer TMA formed the Physician Oncology treatment, and genetic cancers. All Education Program (POEP) in 1987 to these topics have been approved for carry out the recommendations of the AMA PRA Category 1 Credits™, Texas Cancer Plan regarding physician including ethics and/or professional education. POEP is funded in large part responsibility. Physicians and other by the Cancer Prevention and Research health care professionals may Institute of Texas and is directed by a download the items free of charge; steering committee of experts focused however, there is a small fee for those on all facets of cancer prevention wishing to receive continuing medical and control. Since its creation, POEP education (CME) credit for their has provided cancer prevention and participation. screening training to more than 100,000 Texas physicians and other professionals. Speakers’ Bureau TMA’s Physician Oncology Focus Education Program Speakers’ Bureau encompasses more than 100 cancer POEP’s focus is educating primary experts across the state who volunteer care physicians about state-of-the- their time to speak to physicians and art advancements in science and other health care professionals on technology as they relate to cancer cancer prevention, screening, early prevention, screening, early detection, detection, and control issues. Many control, and survivorship issues, lectures are approved for CME credit, including the physician role in including ethics. influencing behavior. It’s easy to request a POEP speaker. Contact us with your topic choices Educational Materials and ideal dates for programs. We recommend 60 to 90 days lead time POEP has developed cancer education for the recruitment of speakers. The resources and clinical tools for POEP staff will contact members of practicing physicians to enhance their the Speakers’ Bureau to determine ability to reduce cancer morbidity and availability for the requested dates and mortality in Texas. coordinate the speaker’s schedule. We provide educational posters and POEP reimburses the speaker for travel, pocket guides on cancer screening lodging, meal expenses, and any fees guidelines, tobacco cessation, skin associated with his or her services. In cancer, and human papillomavirus some cases, we may be able to assist vaccination. These items are available with costs associated with room rentals, at no cost for Texas medical offices. audio-visual needs, and production of supplemental materials. There is no In addition, our website offers home cost to the requesting institution or study and Internet-based courses on organization.

2 Target Audience Hour Designation “Primary Care Update: Cervical Cancer” The Texas Medical Association is designed for primary care physicians designates this educational activity for a and physician assistants. maximum of 1.5 AMA PRA Category 1 Original release date: July 1, 2010 Credits™. Physicians should only claim Expiration date: July 1, 2013 credit commensurate with the extent of their participation in the activity. Instructions for Completing TMA has designated “Primary Care This Course Update: Cervical Cancer” for 1.5 hours Physicians who complete the entire of education in medical ethics and/or activity, including the knowledge professional responsibility. assessment and evaluation, may receive continuing medical education Author Disclosures of credit. To receive credit, please mail Commercial Affiliations the assessment, the evaluation, and Policies and standards of the payment in the amount of $25 to POEP, American Medical Association and the 401 W. 15th St., Austin, TX 78701, or fax Accreditation Council for Continuing the documents (including credit card Medical Education require that authors information) to (512) 370-1693. of continuing medical education articles If you have any questions, please disclose any relevant financial interest, contact Laura Wells at (512) 370-1673 or relationships, or affiliations they may [email protected]. have with commercial entities whose The expiration date for this activity products, devices, or services may be is July 1, 2013. TMA considers the discussed in their articles. The planners postmark or date stamp the completion and authors of this module have date of the activity. Items postmarked advised the Texas Medical Association or faxed after the expiration date that they have nothing to disclose. will not be considered for continuing Salvatore LoCoco, MD medical education credit. Chair, Department of Obstetrics and Gynecology Funding University of Illinois, College of The Physician Oncology Education Medicine at Peoria Program is funded primarily by the Table of Contents Cancer Prevention and Research Learning Objectives Introduction...... 4 Institute of Texas. Upon completion of this activity, Pelvic Exenteration...... 4 participants should be able to: Rates of Incidence, ...... 4 Accreditation 1. Associate cervical cancer with Death, and Survival The Texas Medical Association is the incidence rates of human Case Study: Teen-Aged ...... 7 accredited by the Accreditation Council papillomavirus, Patient for Continuing Medical Education to 2. Appraise a patient’s risk of cervical Guidelines Are Just That...... 7 provide continuing medical education cancer, Staging Cervical Cancer...... 8 for physicians. 3. Cite countries with the highest rates Case Study: Patient Presents ...... 9 of cervical cancer, and Surveillance Challenges Barriers to Follow-Up Care...... 10 4. Integrate strategies for surveillance challenges. Case Study: When a Patient ...... 11 Falls Through the Cracks Treating Extrapelvic Disease...... 12 Need for Communication ...... 12 and Education Education About the HPV ...... 12 Vaccine Knowledge Assessment...... 14 “Primary Care Update: ...... 14 Cervical Cancer” Evaluation

3 Pelvic Exenteration 1957-88, the survival range was 34-45 ince the time of Hip- percent. From 1989 to present, cumula- pocrates, cervical cancer In 1950, Alexander Brunschwig, MD, tive statistics in the literature still report has been thought incurable. published his initial work on pelvic only a mean of 33.8-percent five-year 1 Indeed, this cancer is as exenteration. A pelvic exenteration is survival. Slethal to women in many parts of an extirpative surgical procedure used These are salvage (oncology code the world today as it was 50 years to remove extensive local and regional word for achieving long-term remission ago, and likely even 100 years ago. cancer of the female genital tract, most or cure) statistics that represent only Fortunately today, through early commonly advanced or recurrent potential for survival for cervical cancer detection, diligent surveillance, cervical cancer. Typically the surgery patients who have lived long enough and advanced surgical techniques, entails an ultra-“radical” excision of the to experience a treatment failure (and we are learning to make inroads cervix, uterine corpus, parametrium, thus become candidates for pelvic into treating this terrible disease. and ligamentous supports that are exenteration). Current state, national, But even in the United States, and structurally and functionally attached to and worldwide trends illustrate the true certainly in Texas, many women the pelvic bones and muscles. In many magnitude of this cancer’s severity. are unable to get the treatment instances the bladder and rectum must they need. be resected in order to achieve “clear” margins. The goal of the procedure is Comparing statistics on cervical surgical cure. Reconstruction includes Rates of Incidence, Death, cancer incidence and survival from urinary and fecal diversion to an incon- decade to decade and between and Survival tinent ventral stoma. Modern surgical cities, states, countries, and conti- The Surveillance, Epidemiology and techniques allow for restoration of a nents is not as easy as one might End Results Program estimated inci- continent urinary stoma such as a Mi- expect. Many health professionals dence of new cancers of the “cervix ami pouch and reanastomosis of recto- involved with women’s health care uteri” in the United States in 2009 to sigmoid colon. For women desirous of feel that most reported cervical be 11,270 cases and 4,070 expected maintaining a functional vagina, plastic cancer statistics for incidence and deaths. The World Health Organization surgical harvesting of musculocutane- death rates essentially boil down (WHO) estimates that 473,000 cases ous grafts allows for a neovagina. to “educated guesses.” Because will occur worldwide this year with this disease occurs much more Table 1 shows Dr. Brunschwig’s re- 253,500 deaths expected;2 here in the frequently in those with lower so- ported morbidity and survival statistics Western Hemisphere, the Pan Ameri- cioeconomic status — and limited in his first 100 patients. Seventy-nine can Health Organization reported in access to care — there appears to were dead of disease by 12 months, 2007 that 74,855 deaths occurred from be underreporting of actual cases. and only 13 percent were alive by cervical cancer in 13 Latin American There likely is a sizable group of 33 months. Compare this with the countries between 1996 and 2001. unscreened patients who typi- summary of the published modern Figure 1 shows the Western Hemi- cally gain entry to the health care literature on pelvic exenteration in the sphere population concentrations of system through an emergency same table. Over the 30-year interval of cervical cancer patients. department, by which time they are found to be symptomatic from more advanced disease. Table 1: Cervical Cancer Survival After We do recognize, however, that Pelvic Exenteration cervical cancer is not a disease Perioperative Mortality (%) Cause of Death just found in the poor. Because transmission of the human papil- Dr. Brunschwig’s Data lomavirus (HPV) is ubiquitous, this 1950 (N=100) 20% (< 30 days) Uremia, sepsis disease affects women of all ages 49% (< 8 months) 36/49 metastasis, uremia and all walks of life. The diagnosis 10% (> 8 < 12 months) 8 with metastasis of cervical cancer in the life of a woman at any age is life-altering 13% (12-33 months) 13% survival at 33 months to say the least, and frequently Published Modern Literature still means premature death. Few clinicians practicing in the trenches 1957-88 14-24% 34-45% 5-year survival today would agree that monitored 1989-present 2-10% 23-61% 5-year survival modern epidemiologic trends truly Mean survival of 33.8% convey the magnitude of devas- tation this disease imposes on women, their families, and their communities. 1. Brunschwig A, et al. Partial and complete pelvic exenteration. AJOG. February 1950; 59 No. 2:972-74. 2. Disease and injury country estimates. World Health Organization. 2009.

4 Figure 1: Cervical Cancer Population Density in Western Hemisphere3 Cervical Cancer Incidence Rates in North, Central, South America and the Caribbean

The Bahamas

Cuba Turks and Caicos Islands Canada Dominican Cayman Islands Republic U.S. & British Haiti Virgin Islands

Jamaica Puerto Rico U.S.A.

Netherlands Antilles The Caribbean Mexico Trinidad and Venezuela Tobago Central America Guyana Suriname Guatemala Colombia French Guiana Belize Ecuador Honduras Brazil < 10.0 Peru 10.0 < 20.0 Nicaragua Bolivia El Salvador Chile 20.0 < 30.0

Paraguay 30.0 < 40.0 Costa Rica Uruguay 40.0 < 50.0 Argentina Panama 50.0 < 60.0

60.0 < 70.0

> 70.0

Data Not Available

In Texas, 5,298 cases of invasive cervi- never make it into a hospital-based cal cancer were reported to the Texas tumor registry, and some, as noted Department of State Health Services 4 above, are so advanced at diagnosis cancer registry during 2002-06, an that they are admitted to the hospital incidence of 9.7 per 100,000 women with life-threatening end organ involve- (Figure 2, page 6). The U.S. incidence ment, and the cervical cancer diagnosis is 8.7 annually, and estimated incidence is never confirmed. in Mexico is 40.4, explaining why During the same reporting period, border communities such as El Paso 1,702 deaths occurred in Texas from experience a much higher incidence invasive cervical cancer, an overall than the rest of the state at 15.3 per death rate of 3.4 per 100,000 5. By com- 100,000 women. Many consider the parison, the U.S. annual rate of death Texas numbers to be an underestimate is 2.5 per 100,000 women. Texas ranks of the true incidence mainly due to the seventh nationally in annual incidence functional limitations of reporting to and ninth in annual mortality.6 the statewide database. Some patients

3. Lewis, MJ. A Situational Analysis of Cervical Cancer in Latin America & the Caribbean. Pan American Health Organization. 2004. 4. Texas Department of State Health Services, Cancer Epidemiology and Surveillance Branch. Submission Nov. 26, 2008. 5. Texas DSHS. 6. Data from the National Vital Statistics System.

5 Figure 3 shows that death rates from Figure 2: Incidence Rates of Cervical Cancer in Texas invasive cervical cancer are 4.9 in El Paso, and 5.5 and 6.4 in Cameron and Webb counties respectively. By comparison with other cancers such as lung, breast, and colorectal cancer, these numbers do not seem excessive; however, we would be remiss in our discussion of the current understanding of cervical cancer if we did not focus attention on the pragmatic realities of what it means in 2010 to be newly diagnosed with cervical cancer. It has been said that given the state of medicine today in a country such as the United States, women should not have to die from this cancer. For years we have understood the pathophysiology. We can screen for the precancerous condition and treat it. We even have an effective preventive treatment, HPV vaccination. In fact, there has been a 50- percent reduction in occurrence and death from cancer of the cervix uteri between 1975 and 2006. Texas medical pioneers such as Felix Rutledge, MD, and Gilbert Fletcher, MD, from M.D. Anderson Cancer Center helped formalize the training of gynecologic oncology surgeons and radiation oncologists to standardize a very effective multidisciplinary treatment approach using radical surgery and/or radiation therapy. Still, in spite of a significant amount of medical resources and funding devoted to screening and treatment in Texas, especially in the public sec- tor, our incidence at 9.7 is 50 percent greater than the age-adjusted U.S. rate of 6.5. 7 Texas mortality is 20 percent higher than the national average. Rec- ognizing that we can and must perform better for the sake of all Texas women and their families at a local and state level, we are going to exam- ine, through a case-based approach, the impact of a new diagnosis of cervical cancer on a woman’s life.

7. Rates are age-adjusted to the International Agency for Research on Cancer world standard population. 6 Figure 3: Death Rates in Texas From Cervical Cancer Case Study: Teen-Aged Patient The first patient is an 18-year-old woman who was referred by her general gy- necologist with a tissue biopsy of a cervical lesion that showed carcinoma in situ, “cannot rule out invasion.” Upon presentation to our gynecologic oncology clinic, a 3.0 x 2.5 cm. exophytic growth was visible without a colpo- scope, and a deeper biopsy was taken of the leading edge at the transformation zone. Histologically, a moderately differentiated (grade 2) squamous cell carcinoma was confirmed. Guidelines Are Just That In the context of current thinking and public discussion in recent months about the guideline changes for cervical cancer screening, this patient’s case illustrates the need to be diligent and responsive in evaluating individual patients by their presenting signs and symptoms as opposed to just following “cookbook” guidelines. Remember, guidelines serve as recommendations for a framework to screen asymptomatic patients in the general population. Table 2 (page 8) is a review of the new American Cancer Society cervical cancer screening recommendations. As a teenager, this patient clearly falls outside the expected norms. However, she presented with a several-month history of postcoital spotting and discharge and was properly evaluated with thin prep cytology and a biopsy. One can argue that the Pap smear was not necessary because she had a visible lesion. She needed only a biopsy with or without colposcopic direction; the Pap is intended to be a screen of asymptomatic, normal patients only. Further history on the patient finds that she is gravida 2 para 2 and 21 months postpartum from her second vaginal delivery. She experienced coitarche at age 13 and delivered her children at age 16 and 17. She had an ASCUS Pap smear after her first pregnancy and negative colposcopy and negative endocervical curettage. The patient was also a nontobacco user, had no history of substance use, and reported a history of three sexual partners in her life. She had no prior history of HPV genotyping.

7 Table 3 is a review of the known risk Table 2: Screening Guidelines factors associated with the development of cervical cancer. The patient in ques- Summary of New Cervical Cancer Screening Guidelines tion has a number of these risk factors (American Cancer Society) including early age of intercourse; 1. Cervical cancer screening should begin about three years after a multiple sexual partners during early woman begins having vaginal intercourse, but no later than 21 years maturation of the genital tract; and of age. likely, although impossible to confirm, high-risk HPV exposure. Any practicing 2. Cervical screening should be done every year with regular Pap tests primary care physician, advanced nurse or every two years using liquid-based Pap tests. At or after age 30, practitioner, or physician’s assistant women who have had three normal test results in a row may get must have a working knowledge of risk screened every two to three years. A doctor may suggest getting the factors if he or she is going to provide test more often if a woman has certain risk factors such as HIV annual well-woman care and gyneco- infection or a weakened immune system. logic cancer screening. Patients with 3. Women 70 years of age and older who have had three or more normal multiple risk factors need regular access Pap results in the last 10 years may choose to stop cervical cancer to care to receive proper evaluations in screening. a timely manner so that cervical cancer might be diagnosed and treated as 4. Screening after a total hysterectomy (with removal of the cervix) is early as possible. not necessary unless the surgery was done as a treatment for cervical cancer or precancer. Some other special conditions may require Survival statistics are improved with continued screening. Women who have had a hysterectomy without early diagnosis and treatment (Table removal of the cervix should continue cervical cancer screening at 4). Treatment morbidity is usually least until age 70. lessened as well, and it is less likely a patient’s cancer will recur and require an exenterative type procedure. Staging Cervical Cancer What does staging mean for this patient Table 3: Risk Factors now that the cancer is diagnosed? What Risk Factors for Cervical Cancer (American Cancer Society) is the next step? The International Federation of Gynecology and Early coitarche Obstetrics, in collaboration with WHO Multiple sexual partners and with input from 124 international High-risk HPV exposure societies about treating gynecologic Tobacco use cancers, has set basic standards for the staging of gynecologic malignancies. Sexually transmitted diseases such as chlamydia and HIV In the United States, all hospitals and DES (diethylstilbestrol) exposure and family history of cervical cancer tumor registries follow the American Multiple pregnancies Joint Committee on Cancer TNM Stag- Dietary factors 8 ing System . The two systems have Hormonal contraception similar criteria. The main purpose for Possible genetic link to HLA-B7 staging is to standardize how we com- municate with regard to breakdown of patients by extent of disease, response to treatment, and survival. The important thing to note for data interpretation is extent of disease prior to treatment and subsequent response to treatment. From WHO’s perspective, staging criteria have been kept as simple and as technologically free as possible. Since cervical cancer is a worldwide problem, and many countries do not have sophisticated equipment for diagnosis and staging, the patient’s stage is assigned clinically. The physician conducts a physical exam to determine tumor size and local extension of tumor, cystoscopy and proctoscopy for 8. The TNM Staging System is based on the extent of the tumor (T), the extent of spread to the lymph nodes (N), and the presence of metastasis (M). Source: American Joint Committee on Cancer. 8 Table 4: Cervical Cancer Staging and Survival Rates Case Study: Patient Presents Surveillance Challenges Stage Description Survival Rate* Our next patient is a 42 year old who Tis In situ, no invasion 93% presented with a vaginal hemorrhage I A Microscopic invasion 93% and hemodynamic instability to the I B Visible tumor, confined to cervix 80% emergency room of the main hospital II A Tumor growth beyond cervix onto vagina 63% of a moderately populated, relatively poor rural county adjacent to an urban II B Parametrial extension 58% county. The patient received fluid III A Tumor extends to lower 1/3 of vagina 35% resuscitation, six units of packed red III B Pelvic sidewall extension with/without 32% blood cells, and fresh frozen plasma, IV A Tumor has direct extension into rectum or bladder 16% and was stabilized and transferred to ureteral obstruction the tertiary referral private hospital after IV B Distant metastases 15% being found to have a large necrotic tumor of the cervix and vagina. The *Survival data from the National Cancer Database from patients diagnosed between 2000 and patient was indigent and morbidly 2002. obese and had been receiving “guid- ance” from a free clinic for her type II insulin-dependent diabetes mellitus larger lesions if necessary, and a simple urinary collecting system. Her assigned and hypertension. She was unem- urologic imaging study using computed stage is IB1 (Table 4). Most cervical ployed and lived with her mother, who tomography (CT scan) when available cancers less than stage IB2 are ame- also was chronically ill. An attempt or IV pyelography. Nodal assessment nable to surgical treatment alone. This was made to transfer her to the county is not a part of clinical staging. Posi- patient had a traditional type III radical hospital of the urban community; 9 tron emission tomography (PET scan) hysterectomy and bilateral pelvic however, transfer was denied because is rapidly becoming a very useful and lymphadenectomy. The surgery the patient lived “out of county.” When reliable part of patient assessment, was uncomplicated; her parametrial we received the patient in our intensive especially in the face of advanced margins were negative as were her care unit, she was still bleeding around disease or to determine whether a lymph nodes. a vaginal pack. This is a very common patient has extrapelvic occult disease. Table 4 is a simple breakdown of presentation for a cervical cancer that Prior to the availability of PET/CT scan- actual survival by stage from data is locally advanced. We (gynecologic ning, patients were treated for what on patients reported to the National oncology and radiation oncology) took was thought to be early-stage disease Cancer Database between 2000 and her to the operating room for an exam with either a radical hysterectomy and 2002. Because all stage IB tumors are under anesthesia, cystoscopy, and proc- pelvic lymph node dissection or whole grouped together in this table, the toscopy. We confirmed the presence pelvic radiotherapy for cure. Patients expected outcome in this case is listed of a 5.5 x 6.0 cm. exophytic, friable would achieve good pelvic control of as a five-year survival of more than 80 squamous cell carcinoma with central the disease and then subsequently fail percent. However, if we look at other necrosis. The tumor extended onto the treatment because of unrecognized prognostic features such as grade 2 anterior vagina by direct extension, giv- retroperitoneal nodal disease or occult histologic differentiation and the ing her a clinical stage IIIA squamous metastases. If we acquire accurate absence of lymph vascular space cell carcinoma of the cervix (see Table knowledge of the extent of disease, invasion (LVSI), expected survival can 4). Computed tomography and a chest then we have the ability to modify be as high as 87-90 percent. x-ray had been obtained. There was or “individualize” treatment plans to no ureteral obstruction, no suspicious Preinvasive, microscopic, and low- extend radiation fields, surgically excise lymphadenopathy, and no extra pelvic volume macroscopic disease (stages I0 isolated nodes, or give radiosensitizing metastatic disease. chemotherapy for disease that would through IB1) has a very good progno- have been ignored in the past. Herein sis. Stages IB2 through IIB have inter- Our first objective with a patient such lies the major failing of the clinical stag- mediate survival outcome that averages as this is to clinically stabilize her and ing system. When patients fail, we have 50-60 percent. Advanced stages III and initiate therapy as soon as possible. The to ask ourselves: Is it due to inadequate IV do relatively poorly, with not only intent is twofold: to alleviate the imme- treatment or because we missed dis- low survival rates but also fairly sig- diate life-threatening symptoms and if ease at the beginning? nificant treatment side effects for many possible achieve a clinical remission. As of these patients. Most efforts to treat noted in Table 1, the expected survival Our 18-year-old patient, for example, these patients rapidly become palliative for this stage of cancer is in the order had a visible lesion less than 4 cm. for symptom management. Fortunately, of 35 percent at five years. To offer pa- confined to the cervix. There was no our patient remains disease-free three tients every possible chance for surviv- involvement of the bladder, rectum, or and a half years after her surgery. al, it is very important to have accurate information on the extent of disease 9. Piver, MS et al. Five Classes of Extended Hysterectomy of Women with Cervical Cancer. 44:265, 1974. so we can initiate therapy as quickly

9 as possible. (Many people outside the and, as in this case, sometimes do not mild skin reaction and discoloration of realm of gynecologic oncology — even take them or defer to another facility. her panniculus from radiation. At the those in health care — are surprised Currently in Texas, patients receiving completion of therapy, patients like to find that as many as one in three tertiary care services for diseases such this one are assessed for any residual of these types of patients will survive as cancer may have to leave their coun- central tumor; if disease-free, they long term.) For this patient, we placed ty because many of those services are can enter a surveillance regimen used a foley catheter and packed the tumor not available (even though each county by most programs that includes an tightly with as much Kling gauze as is responsible for the health care of its oncologist office evaluation every three possible. She was “simulated” (the term indigent population). For years, M.D. months for two years, followed by six- for radiation treatment planning) and Anderson has served as the safety net month evaluations through five years. began her first fraction of whole pelvic, for all indigent cancer patients in the Future imaging is based on clinical external beam radiotherapy that day. state. The burden has become too great findings. This happened, as is usually the case, fiscally for one institution to bear. As This patient’s situation illustrates the to be a Friday, but due to the symptom- part of the current national debate over need for primary care physicians atic hemorrhage she received radiation health care, Texans involved in public (PCPs) to be familiar with surveillance treatment fractions daily throughout the health must advocate for agreements strategies. Frequently, oncologists have weekend. After 48 hours, we removed that promote cooperation between the to coordinate follow-up with the PCP, the vaginal pack to find the acute counties in a statewide regional cancer and they attempt to maintain a liberal, bleeding had arrested. On that Mon- network of at least the major public in- open-door policy, especially in the day, we began radiosensitizing che- stitutions. A public-private partnership first several months after treatment motherapy in the form of single agent probably would facilitate more timely has been completed. Patients who fail cisplatin at a dose of 40mg./M2 (total access to care. therapy locally have a fairly narrow dose of 70 mg.) intravenously. Current This patient presented another chal- window of opportunity for salvage. We treatment recommendations are that if lenge because neither she nor her treat central recurrences or persistence patients do not have surgically ame- mother was able to drive, and the of disease today as Dr. Brunschwig pio- nable disease, weekly cisplatin is to be cancer center was 40 miles away. neered it in 1950, by ultraradical surgi- given along with fractionated radiation. Fortunately, the American Cancer cal removal of the affected tissue, a pel- We have mature data from the Radia- Society11 has a framework of volun- vic exenteration. The goal is to remove tion Therapy Oncology Group protocol teers in place to help ensure all cancer any residual disease with a healthy 90-01 that shows superior survival with patients have transportation for treat- margin of tissue to ensure the cervical 10 chemoradiation. At the completion of ment and surveillance. This patient was cancer has been removed. (PET scan- this patient’s first five radiation treat- planned to 28 total fractions of radio- ning helps us select out patients with ments and her first cycle of chemotherapy to the pelvis to a total dose of extrapelvic disease and spare them the therapy, she was doing well enough to 5,280 cGy, along with weekly cisplatin obvious extensive surgical morbidity go home. infusion followed by intracavitary in the face of disease that is deemed Barriers to Follow-Up Care brachytherapy to deliver an ablative incurable.) This surgery traditionally is dose of radiation to the central tumor. accomplished through a laparotomy; While it seems simple enough to con- In addition, she required narcotic anal- however, as we are able to perform vert a patient from inpatient therapy to gesia for some time while on treatment more and more radical procedures via ambulatory status, arranging this for as well as a couple of outpatient visits a minimally invasive approach, the an indigent patient from a poor rural to the infusion center for hydration surgical “trauma” of this procedure con- Texas county was challenging, to say and another transfusion. The logistical tinues to lessen. The availability of the the least. complications, not to mention the costs daVinci® Robotic device manufactured Most oncologists, whether surgical, of care for a patient like this, are exor- by Intuitive Surgical, Inc. has given our gynecologic, radiation, or medical, bitant. Every bit of her care had to be program a sophisticated surgical device are willing to treat unfunded patients. approved, requested in advance, and to perform technically precise radical The professional fees are easy enough ultimately donated. Morbidity for this surgery using three 8 mm. incisions for to donate, since they actually place patient included pain, bleeding, and the robotic arms and two 12 mm. inci- demands on the physicians’ time. The stress incontinence, all related to the sions, one for the camera port and the technical costs of imaging, delivery of presence of the tumor. Treatment-relat- other for the surgical assistant. See the chemotherapy, ancillary drugs, and ed side effects were excessive nausea, photo comparison in Figure 4 to see radiation therapy frequently are expen- occasional emesis after cisplatin infu- the difference in accessing the abdo- sive and require participation of third- sion, and some diarrhea and cramping men for the same procedure in two party entities, many of which have no due to enteritis from radiation, plus a different patients. obligation to provide services. Coordi- nation of these services can be a logis- 10. Morris M, Eiffel P, et al. Pelvic Radiation with Concurrent Chemotherapy versus Pelvic and Para-Aortic Radiation Therapy for High- tical nightmare and requires dedicated Risk Cervical Cancer (a randomized RTOG clinical trial). NEJM. 340(15): 1137-43, 1999. and motivated social workers, nurses, 11. See www.cancer.org. and physicians. Hospitals are under no legal obligation to accept these patients 10 Figure 4 more a month than she was allowed for coverage. She understood that her Traditional Exenteration Robotic Exenteration follow-up after treatment called for physician evaluations according to the standard schedule above. After her first three-month evaluation, she was lost to follow-up. This is a worrisome problem for most of us in cancer care, especially early in the patient’s post-treatment course because many early loco-regional recurrences are salvageable. During the following six years she had five separate admissions to the hospital for bowel symptoms. She usually reported several days of nausea and emesis and eventually would present to any one of three emergency depart- ments in the urban community where she lived. Because she did not have The patient in this case study, after treatable recurrence and overtesting to regular medical supervision, no single 13 months, developed central the point of causing continuous fear physician or hospital got to know her progression of her cancer involving of death. The latter sometimes creates well. This patient’s bowel symptomatol- the cervix, upper vagina, and bladder. unnecessary paranoia in patients and ogy actually is typical of patients who She was one of our first patients to their families, even when the patient is have been cured of cervical cancer whom we offered a robotic approach doing very well. using modalities of both radical surgery for her anterior exenteration. Much and radiotherapy.13 The suspected to our surprise, we were able to Case Study: When a Patient pathophysiology is that of a chronic, completely remove the disease with Falls Through the Cracks subacute, small bowel obstruction. the robotic instrument.12 The impact The story of this next patient illustrates After radical pelvic surgery, adhesive of the surgery on the patient’s life was the abovementioned dilemma. She is disease can be a problem for some coping with urinary diversion and a 29 year old who was diagnosed at patients. Adhesions can form between fecal diversion, not to mention the the age of 20 with a Stage IB1, grade the rectum and sigmoid colon to the psychological trauma of fear over 2 squamous cell carcinoma of the exposed retroperitoneum or vaginal future recurrence and ultimate mortal- cervix. Her original private gynecologic cuff. Chronic symptoms with periodic ity. She died from disease at 40 months oncologist performed a type III radi- exacerbations seem to generally wors- from diagnosis with distant metastases. cal hysterectomy on her and bilateral en when terminal ileum is involved. While following patients who have pelvic lymphadenectomy. She had clear Once these adhesions have formed, been treated for cervical cancer, one margins but had two positive pelvic loops of small intestine become fixed must strike a balance between being lymph node metastases. After her surgi- to certain areas of the pelvis, pre- diligent about surveillance and help- cal recovery she received whole pelvic cluding normal peristalsis. If we add ing the patient maintain as normal a external beam radiation therapy to treat radiation to the mix, patients can find quality of life as possible. The key to the regional “field.” She did not receive it impossible to live a normal life due helping survivors live with a history of radiosensitizing chemotherapy because to chronic abdominal pain and an in- cancer is to not treat them like “cancer that was not the standard in 1999 when ability to maintain proper nutrition. In patients” while they are disease free. she was treated. She tolerated therapy the mechanism of action in radiation, Also, in a medical system today that is well with no significant sequelae other the affected tissue goes through regular so driven by “cookbook” algorythms, than some nausea and diarrhea during cycles of inflammation and repair as we have to remember that we, as phy- her pelvic radiation. When she turned the fractionated doses are delivered sicians, are here to serve the needs of 21, she went off her parents’ insur- five days a week over five weeks. At our patients. They are not here to serve ance and was not eligible for cover- a microscopic level, the tissue in the us, our office staff, or our protocols. age through her employer because treatment field is devascularized. This Oncologists have to strike a balance of the preexisting cancer condition. ultimately interferes with normal bowel between gathering appropriate infor- She applied for public aid through the or bladder function after treatment. mation in a timely manner to detect a county but learned that she made $150 If that happens to a single loop of bowel fixed to the pelvis by adhesions, patients can experience this type of 12. LoCoco, SJ. Feasibility of Pelvic Exenteration Utilizing the daVinci® Robotic Device, A Case Series. Oral presentation, Western Association of Gynecologic and Gynecologic Oncologists of Canada. Vancouver, June 2009. complicated course. The good news 13. Cola, LR, et al. Late effects of radiation therapy on the gastrointestinal tract. Int J Radiation Oncology Biology and Physics. 5: for patients receiving modern treatment 1213-36, 1995. schema with new-generation linear accelerators is that toxicity to 11 normal tissues is much less than what Today, we take a more individualized treating specialists in the urban areas was seen historically. approach to planning treatment for often must rely on the family doctors, With this understanding, those of us known disease. PET scans in squa- internists, pediatricians, and general in the gynecologic oncology commu- mous tumors have been found to be surgeons who tirelessly serve Texans nity are fairly rigid in getting to know extremely reliable over the last four on the front lines at great personal our patients after they have completed to five years. In certain instances, this sacrifice. Collectively, specialists and treatment. The continuity is essential to knowledge has allowed us to be more subspecialists such as gynecologic advising patients who are experiencing aggressive locally for cure than we oncologists have tried to maintain good symptoms. The key is to discern when would have been in the past. lines of communication to the referring to manage conservatively and when Anyone with experience of caring for physicians in the outlying areas. No to intervene surgically, while making cervical cancer recognizes that the one would argue that, with the rela- sure the symptoms are not from recur- prognosis for our patient in this case tive physician shortage and disparity rent disease. This patient is a prime study is poor. However, if theoretically of available resources and manpower example of how patients who fall this is a late recurrence, biologically between the urban and rural areas through the cracks can wind up with this has to be a slow-growing tumor. If of the state, we have to get better at more intervention than necessary and it is limited to the area identified on the coordinating services if we are going add costs to an arguably already over- PET scan, perhaps this disease can be to improve patient outcomes. Treating whelmed system. This patient wound eradicated. This is where a multidisci- malignancies such as cervical cancer up with three exploratory laparotomies plinary approach to treatment decisions depends on proper screening, stag- by nongynecologic oncology services is critical. In planning with a radiation ing, and treatment. Ready and efficient with no disease ever found. When oncologist who had extensive knowl- lines of referral and patient transfer our service became involved with her edge and experience in the disease, must be established to ensure timely care through another emergency room we chose to treat the affected area, left and universal access to cancer care evaluation in 2008, we were able to upper lung, hilum, and mediastinum, services. This is essential to optimizing manage her chronic bowel enteritis with intensity-modulated radiation outcomes for Texas patients. During conservatively with nasogastric decom- therapy. We considered chemosensitiza- my time serving on the Texas Medical pression and hydration over a five-day tion with cisplatin during radiation but Association steering committee for the hospitalization. were concerned about patient tolerance Physician Oncology Education Program to treatment in this area and decided to (POEP), it became clear that POEP is This patient was chosen for discussion an underutilized resource for helping to for another reason. During this admis- give cytotoxic chemotherapy for four 15 bridge the gap among Texas physicians. sion, a computed tomography scan was cycles with cisplatin and topotecan after radiation. This patient completed The internal structure of the committee performed of her thorax (because she is organized into two segments, one had a chronic, dry cough), abdomen, therapy without delays. It is now nearly two years after completion of her treat- for monitoring patient care trends, and and pelvis. She was found to have an one for devising educational programs isolated 3.3 cm. lesion in the left upper ment, and she is asymptomatic and remains disease free. We have made and materials for physicians as well as lobe of her lung, which was confirmed midlevel providers in cancer. by biopsy to be squamous cell car- sure that she has not gotten lost to cinoma. This was nearly nine years follow-up. We have her on an effective Education About the after discovery of her primary cervical bowel regimen that has kept her out HPV Vaccine cancer. Because she was a nonsmoker of the emergency room and out of the operating room. She is now working An example of how TMA and POEP, with no other relevant medical history the latter now overseen by the Cancer or exposures, we regarded this new and has qualified for health insurance through her employer. and Prevention Research Institute of development as a late recurrence, not Texas (CPRIT)16, have been successful a new primary cancer. We assessed in assessing a trend and subsequently her for any other disease using PET/ Need for Communication implementing an educational initiative CT scanning and found a small lymph lies in the area of HPV vaccination. node in the hilum of the affected lung. and Education This topic is now an important part of Treating Extrapelvic Disease Review articles such as this are impor- any discussion of cervical cancer; after tant to foster improved communication decades of treating patients with the Our thinking has evolved over the between specialists and primary care same tools and strategy, we finally are last two decades when it comes to physicians. In our large state of Texas, able to talk about the real probability of treatment planning for a patient with with many communities and regions prevention. We now know after years extrapelvic disease. This type of patient served by small numbers of medi- of study and research that the large traditionally would have been con- cal professionals, patients and their majority of invasive cervical cancers sidered incurable, given a fairly toxic multidrug chemotherapy regimen until 14 Brader KR, Morris M, Levenback C et al. Chemotherapy for cervical carcinoma: factors determining response and implications for she progressed, and died. Even though clinical trial design. J Clinical Oncology. 1998; 16: 1879. dozens of cytotoxic agents have been 15. Long HJ III, Bundy BN, Grendys, EC Jr., et al. Randomized phase III trial of Cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clinical Oncology. 2005; 23(21): 4626-33. studied in recurrent cervical cancer, the 16. Formerly, POEP was under the oversight of the Texas Cancer Council. most active agent to date is cisplatin.14 12 are caused by a viral infection of the Useful Internet Resources genital tract. Statistics suggest that as much as 70 percent of invasive cervical American Cancer Society cancer worldwide is a result of HPV www.cancer.org type 16 and 18 17. As noted above, other Centers for Disease Control and Prevention genetic and behavioral risk factors www.cdc.gov/std/hpv make some patients more susceptible Cure Research.com to developing the disease; something www.cureresearch.com/c/cervical_cancer/treatments.htm in the viral DNA makes it the predomi- nantly virulent epidemiologic agent Lance Armstrong Foundation www.laf.org when it infects the squamocolumnar junction cells of the transformation M.D. Anderson Cancer Center — cervical cancer zone of the cervix. In 2007, the Federal information Drug Administration approved Garda- www.mdanderson.org/patient-and-cancer-information/cancer-information/ sil® based on fairly impressive research cancer-types/cervical-cancer/index.html evidence that it is nearly 100-percent National Cancer Institute effective at eradicating precancerous www.cancer.gov/cancertopics/types/cervical/ genital tract lesions known commonly National Cervical Cancer Coalition as dysplasia18. Prior to Gardasil’s release www.nccc-online.org/ that same year, the POEP Trends Society of Gynecologic Oncologists Committee had already put together www.sgo.org a physician survey to assess general understanding of the science behind The vaccine is safe and noninfectious however it is achieved, ensures that all the vaccine. We also were interested because no viral DNA is used; there- young women in Texas will have ac- in physician sentiment with regard to fore, it is not transmittable.19 The data cess to HPV prophylaxis with the vac- recommending the vaccine as well as from the preliminary trials culminating cine in the hope of one day preventing physician intent to offer the vaccine in with a Phase III clinical trial known this deadly disease. 20 the office. As fate would have it, the as FUTURE II were gleaned from a The most important take-home mes- survey was completed the same time randomized double-blinded study, pla- sage with regard to the HPV vaccine is that Gov. Rick Perry issued an execu- cebo controlled, to determine efficacy. that for the first time ever, we actually tive order mandating the vaccine for In the study, 12,167 women between have a treatment that has real potential admission to school. Unfortunately, the the ages of 15 and 26 received the vac- to prevent cervical cancer. Public health ensuing public controversy over this cine on day 1 and again at two months epidemiologists who have studied the order fairly drowned out the actual and six months. Data analysis showed issue estimate it will take a generation safety and efficacy of the vaccine found 98-percent efficacy in prevention of of vaccinating girls and young women in the premarket trials, and the theoreti- cervical epithelial neoplasia grade 2 or to bring about a major reduction in cal public health probability of elimi- 3, adenocarcinoma in situ, and invasive the incidence of cervical cancer. This nating HPV-related genital tract cancer, HPV 16- and 18-related cervical cancer will require universal acceptance and 21 especially that of the cervix. at the initial three-year endpoint. application of the vaccine. Subsequent POEP uncovered a profound knowl- These data, along with several large strategies for screening will have to be edge gap about the vaccine, which con- series from European studies, are very modified as the incidence of invasive tributed to relatively low planned rates compelling and support use of the vac- and preinvasive lesions diminish, and of administering it at the practice level. cine with the eventual hope of eradi- more and more resources can be al- The vaccine is a noninfectious recom- cating the ravages of cervical cancer. located to prevention. If the dialogue binant quadrivalent vaccine prepared The public discourse at the time, and to continues based on the proper delivery from highly purified viral-like proteins some extent still today, focused on the of scientific information to physicians (VLPs) of the L1 capsid protein of HPV social concerns about recommending in our communities, we can hope types 6, 11, 16, and 18. The L1 proteins the vaccine. Fears were raised about that one day cervical cancer will be are produced by fermentations of Sac- patients getting the infection from the as scarce as smallpox is today. What a charomyces cerevisiae with vitamins, vaccine, or promoting sexual promis- fantastic possibility for the good health amino acids, mineral salts, and car- cuity among young girls if they were of women around the world. bohydrates. Aluminum hydroxyphos- vaccinated. To Governor Perry’s credit, phate sulfate is used as an adjuvant. he recognized that a funded mandate,

17. Lowry DR, Schiller. Prophylactic human papillomavirus vaccines. J Clinical Investigation. 116(5): 1167-1173. 18. Gardasil. U.S. Food and Drug Administration. www.fda.gov. 19. Merck & Co. product manufacturing information. 20. Females United to Unilaterally Reduce Endo/Ectocervical Disease. 21. Koutsky, Laura A. et al. Quadrivalent Vaccine against Human Papillomavirus to Prevent High-Grade Cervical Lesions. NEJM. Vol 356:1915-1927, 2007. 13 Cervical Cancer Knowledge Assessment 1. Cervical cancer survival rates after pelvic exenteration are now 23-61 percent.  True  False 2. Texas ranks ninth nationally in annual cervical cancer mortality rates.  True  False 3. Staging for cervical cancer can involve:  a. Nodal assessment  b. PET scans  c. CT scans  d. All of the above  e. B and C only 4. Twenty-fivepercent of cervical cancer is the result of HPV types 16 and 18.  True  False 5. The American Cancer Society states that screening for average-risk women:  a. Should begin three years after she begins having intercourse but no later than age 21  b. Is not necessary after a total hysterectomy  c. Can stop for women 70 and older with three or more normal Pap results  d. All of the above 6. Risk factors for cervical cancer include:

 a. Tobacco use

 b. Multiple pregnancies 7.

 c. STDs such as chlamydia and HIV 6.

 d. All of the above 5.

False

7. Survival rates are increased for cervical cancer patients 4. e

when they are seen by a/an: 3. True

 a. Surgeon 2. True

 b. OB-Gyn 11.  c. Gynecological oncologist Answers:  d. Any of the above Evaluation Using the five-point scale, please check the rating that best reflects how much you knew about each of the following areas before the course, and how much you know after this activity.

1=Not at all knowledgeable 2=A little knowledge 3=Neutral 4=Some knowledge 5=Extremely knowledgeable Association of cervical cancer with the incidence rates of human papillomavirus Knowledge before activity Knowledge after activity

14 Cervical cancer risk factors Knowledge before activity Knowledge after activity Geographic areas with higher incidence rates of cervical cancer Knowledge before activity Knowledge after activity Strategies for surveillance challenges Knowledge before activity Knowledge after activity Referral to appropriate health care professional for cervical cancer treatment Knowledge before activity Knowledge after activity Efficacy of HPV vaccine Knowledge before activity Knowledge after activity

Will this education improve the quality of patient care in your office? Yes_____ No_____ What barriers do you see in the implementation of this education in your practice?

After completing this course, I will be more likely to recognize possible Yes_____ No_____ symptoms of cervical cancer. Which strategies you will employ if you suspect cervical cancer?

After completing this course, I will be more likely to refer patients to Yes_____ No_____ a gynecological oncologist. The content met objectives. Yes_____ No____ The content was free of commercial bias. Yes_____ No_____ The processing fee for continuing medical education credit for this activity is $25. ❑ Check enclosed ❑ Charge my ❑ Visa, ❑ MasterCard, ❑ AMEX, or ❑ Discover Card No.:

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15 Learn About Cancer Prevention From a Trusted Source

TMA’s Physician Oncology Education Program offers options that are timely, convenient, and informative.

Speakers’ Bureau: Opportunities for oncology education across the state u 100 -plus Texas cancer experts ready to speak to health care professionals on topics including the HPV vaccine, tobacco cessation, the Texas Cancer Plan, and many others. u No cost to the requesting organization. u POEP can assist with the AMA PRA Category I Credit™ CME accreditation process. u POEP pays speaker travel costs.

Online continuing medical education opportunities, including ethics credits

Free resources including pocket guides and office posters

POEP — Increasing Texas physicians’ knowledge, skills, and roles in cancer prevention, screening, and diagnosis

For more information about these opportunities, or to order materials, visit www.poep.org.