Gynecologic Cancers

Early presentation of endometrial cancer permits effective managementwith excellent clinical outcome. The addition of hysteroscopy todilatation and curettage (D&C) in the evaluation of postmenopausalbleeding adds little to the detection of malignancy. Imaging studies suchas computed tomography, magnetic resonance imaging, and positronemissiontomography may be of use in determining the presence ofextrauterine disease in patients medically unfit for surgical staging.However, these studies are not sufficiently sensitive to replace surgicalstaging and have little role in routine preoperative evaluation. Clinicalstaging alone is clearly inadequate, as 23% of preoperative clinicalstage I/II patients are upstaged with comprehensive surgical staging.Preoperative tumor grade from D&C or office biopsy may be inaccurateand lead to an underestimate of tumor progression if used to determinewhich patients should be surgically staged. Clinical estimationof depth of invasion, with or without frozen section, is inaccurate andmay lead to underestimation of disease status when surgical staging isnot performed. The practice of resecting only clinically suspicious nodesshould be discouraged as it is no substitute for comprehensive surgicalstaging. Comprehensive surgical staging provides proper guidance forpostoperative adjuvant therapy, avoiding needless radiation in 85% ofclinical stage I/II patients. Finally, resection of occult metastasis withsurgical staging may improve survival.

The review by Vergote et al[1]presents a well-organized andcomprehensive summary of thedata addressing neoadjuvant chemotherapyfor ovarian cancer. The timingof debulking surgery for thisdisease is a common and clinicallyimportant question, but one that lacksdefinitive trial data. The assembleddata suggest a rationale for decisionmaking.The European Organizationfor Research and Treatment of Cancer(EORTC) and Gynecologic OncologyGroup (GOG) 152 trialspresent compelling evidence supportinga “maximal surgical effort” by anexperienced gynecologic surgeon,preferably at a specialty hospital, atsome point during primary therapy.

Neoadjuvant, or induction, chemotherapyhas been usedextensively in selected carcinomas,particularly head andneck cancer (recently reviewed inONCOLOGY)[1] and locally advancedbreast cancer. Despite beneficialeffects on morbidity, long-termsurvival has not been significantly improvedby neoadjuvant chemotherapy.

Primary debulking surgery by a gynecologic oncologist remains thestandard of care in advanced ovarian cancer. Optimal debulking surgeryshould be defined as no residual tumor load. In retrospective analyses,neoadjuvant chemotherapy followed by interval debulking surgerydoes not seem to worsen prognosis compared to primary debulking surgeryfollowed by chemotherapy. However, we will have to wait for theresults of future randomized trials to know whether neoadjuvant chemotherapyfollowed by interval debulking surgery is as good as primarydebulking surgery in stage IIIC and IV patients. Interval debulking isdefined as an operation performed after a short course of induction chemotherapy.Based on the randomized European Organization for Researchand Treatment of Cancer–Gynecological Cancer Group (EORTC-GCG)trial, interval debulking by an experienced surgeon improves survival insome patients who did not undergo optimal primary debulking surgery.Based on Gynecologic Oncology Group (GOG) 152 data, intervaldebulking surgery does not seem to be indicated in patients who underwentprimarily a maximal surgical effort by a gynecologic oncologist.Open laparoscopy is probably the most valuable tool for evaluating theoperability primarily or at the time of interval debulking surgery.

Few would question the statementthat the role of surgery in themanagement of epithelial ovariancancer is unique in solid tumoroncology.

The management of ovarian cancer entails a complex blend of medicaland surgical interventions. Managing patients with recurrent ovariancancer increases the complexity of therapies and adds palliative interventions.The presence of recurrent ovarian cancer is both emotionally andphysically taxing for patients as well as their caregivers. With an increasinglyinformed patient population, a balance must be achieved betweeneasily accessible information enabling patients to know that they nowhave an incurable disease and support for their hopes and desires to stillovercome their cancer. The decision tree in the management of recurrentovarian cancer blends many different factors. This discussion will separatethose factors as if they are pure elements. We will address managementbased on response to primary therapy and time to recurrence, thelocation of recurrence, symptoms of recurrence, the patient’s histopathology,and the patient’s primary stage as it relates to the extent of diseasepresent at the start of chemotherapy.

In their article, Drs. Michener andBelinson make the case for treatingrecurrent ovarian cancer as achronic disease, with limiting morbidityand providing palliation of symptomstheir major goals. A review ofrecent literature would support their contention and management strategy.The cure rate for patients with recurrentovarian cancer is < 5%, and theaverage patient in the United Statesreceives more than five separate regimensof chemotherapy for recurrentdisease. Previous attempts at aggressivetreatment for recurrent disease haveshown, at best, very modest benefitwith significant expense and morbidity.What we are left with is a strategy oftrying to determine which patients maybenefit from aggressive salvage therapyand which are better managed witha chronic palliative attempt.

The Michener/Belinson articledeals not so much with what isnew in the treatment of ovariancancer, but with the changing managementparadigm. The authorscorrectly point out that one cannotexpect to offer curative options inovarian cancer patients who recur.Consequently, in planning therapy,the focus should be on the ability toprovide a lifelong strategy to controlthe disease through maintenance therapy.After first-line chemotherapy,complete responders have reasonablylong remissions in the absence of anyintervening therapies, but this is notlikely to be the case with recurrentdisease. In fact, Markman et al[1] havestressed that remissions followingtreatment for recurrence are neverlonger than the preceding ones.

In this installment of Second Opinion, we are presenting two cases of tumors of the female genital tract, specifically, the ovary and uterus, which contain both epithelial and mesenchymal components and therefore have unique diagnostic and therapeutic implications. The first has an unusually poor prognosis and the second is notoriously difficult to diagnose.

Ovarian cancer is the deadliestof the gynecologic malignancies.Approximately threequartersof patients present with advanced-stage disease. With aggressivecytoreductive surgery followed byplatinum-based chemotherapy, mostpatients will achieve remission. Despitethis initially good response totreatment, most patients experiencerecurrence and ultimately die of theirdisease. Novel treatment strategies areneeded. Molecularly targeted therapiesoffer the promise of improvedefficacy with decreased toxicity. Inthis article, Drs. Stephanie Blank, RichardChang, and Franco Muggiapresent an excellent summary of thecurrent status of epidermal growth factorreceptor (EGFR) inhibitors in thetreatment of ovarian cancer. They describethe promise of these drugs aswell as some of the questions regardingthe best way to integrate theminto therapy for ovarian cancer.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

SAN DIEGO-For the first time, a combination regimen has shown improved survival over single-agent cisplatin (Platinol) for the treatment of advanced cervical cancer, according to the Gynecologic Oncology Group (GOG) protocol 179, which was presented at the 35th Annual Meeting of the Society of Gynecologic Oncologists (abstract 9).

A review of sentinel node mapping in vulvar and cervical cancer, a technique intended to reduced lymphadenectomy-associated morbidity, and the related controversies.

Iwould like to compliment the authorson an excellent review ofsentinel node evaluation in gynecologiccancer-in particular, vulvarand cervical cancer. The authors havebeen at the forefront of minimally invasivesurgery for gynecologicmalignancies. They have publishedextensively about their experiencewith laparoscopy and radical trachelectomy.Now this group brings forthanother technique that may revolutionizethe way we treat women withvulvar and cervical carcinoma.

By a long-standing strategy,practitioners have sought tolessen the morbidity associatedwith the treatment of pelvic malignancies.With careful understandingof pathologic prognostic factors andthe natural histories of recurrence andmetastatic disease, as well as improvementof imaging studies, there hasbeen a significant reduction in the radicalityof gynecologic surgery.[1-3]

Cervical cancer rates have fallen in the United States; regardless, thedisease remains a significant concern for women, especially those whoare premenopausal. The management of cervical cancer is dependenton stage of disease at diagnosis, and specific needs emerge for patientsboth during and following treatment. Over the past decade, the focus hasbeen to maintain adequate tumor control while reducing long-termnegative consequences. However, problems with sexuality and fertilitypersist for women treated for cervical cancer despite these advances.Sexual dysfunction following treatment for gynecologic cancer hasbeen well documented in the literature, and recent studies demonstratethe success of brief psychosexual interventions. Treatment of sexualdifficulties in cancer patients can be achieved through the provision ofinformation, support, and symptom management, ideally as part of asexual health program. Resources are not always available to developsuch a program. However, medical professionals can identify individualsand organizations with expertise in treating sexual and fertilityconcerns, which can be provided to their patients, making help withthese problems more accessible as needs arise.

Carter et al provide a nice summaryof current knowledge ofsexual dysfunction in and rehabilitationof women with invasivecervical cancer. The prevailing perspectiveof their review, however,seems to be that most women treatedfor cervical cancer are white, middleclasspatients at major cancer centers.In order to make a difference in thequality of life of the majority of cervicalcancer survivors, we have to understandwho they are and recognizethe impact of social and gender inequalityon their lives and relationships.

The importance of quality of lifeduring and after treatment forcervical cancer has been ignoredfor too long. The pervasive attitudethat focuses on cure, withmorbidity an afterthought, is stillparamount in many patients’ and oncologists’minds. However, at the insistenceof patients and families, manyclinicians have recognized and startedto address these issues over thepast 2 decades.

NEW ORLEANS-In women with locally advanced cervical cancer, smoking is an independent risk factor for a significantly worse outcome, a new study from the Gynecologic Oncology Group (GOG) has shown.

ROCKVILLE, Maryland-Physicians can discontinue cervical cancer screening for many women age 65 and older, and delay screening for some young women until age 21, according to new guidelines developed by the US Preventive Services Task Force (USPSTF).

During 1973–1999, both the incidenceof and death rates forcervical cancer decreased byapproximately 50% in the UnitedStates. For 2002, approximately13,000 new cases of invasive cervicalcancer are expected, and approximately4,100 women will die of the disease.Although invasive cervical cancer canbe prevented by regular screening, theprevalence of Pap testing remains relativelylow among minority populationssuch as Hispanic women.

NEW ORLEANS-In the treatment of locoregionally advanced cervical cancer, the addition of cisplatin (Platinol)-containing chemotherapy to a radiation therapy regimen significantly improves overall and disease-free survival, according to RTOG 90-01. Patricia J. Eifel, MD, of the Department of Radiation Oncology, M.D. Anderson Cancer Center, presented the data at the American Society for Therapeutic Radiology and Oncology plenary session (abstract plenary 1).

CHICAGO-Adding paclitaxel (Taxol) and G-CSF support to the standard regimen of doxorubicin and cisplatin (Platinol) improved response rates and increased survival by about 3 months for patients with advanced or recurrent endometrial cancer in a randomized controlled phase III trial conducted by the Gynecologic Oncology Group (GOG) (ASCO abstract 807).

Dr. Grigsby has done a masterful job of summarizing current information on the use of radiation in the management of patients with endometrial carcinoma. In the summary, he offers clear recommendations as to the appropriate management of various subsets of patients-recommendations that are based, at least to some extent, on the data reviewed. Such decision-making based on often incomplete information is necessary in the absence of appropriately designed randomized trials addressing the specific clinical situation. It is important, however, to understand clearly what we actually know and what we deduce from bits and pieces of data.

Dr. Grigsby does an excellent job of summarizing the accepted, stage-by-stage treatment recommendations as well as the controversies surrounding the treatment of endometrial carcinoma. This review is both important and timely, as we have seen the incidence of endometrial cancer increase over the past few years to the point where it is now the most common gynecologic malignancy.

The best clinical outcomes for patients with endometrial cancer seem to be achieved with either surgery alone or a combination of surgery and radiation therapy. Although once administered preoperatively, irradiation is now

Topoisomerase inhibitors have been widely studied for the treatment of refractory or recurrent cervical cancer. Various schedules have been used, with response rates ranging from 13% to 20%. The combination of cisplatin and irinotecan (CPT-11, Camptosar) is being studied in cervical cancer.

WASHINGTON-Health and Human Services Secretary Tommy Thompson has given nine more states the go-ahead to extend Medicaid benefits to uninsured women diagnosed with cancer under the federal Breast and Cervical Cancer Prevention and Treatment Act of 2000.

HOUSTON, Texas-Irinotecan (Camptosar) is active in platinum-refractory cervical cancer and should be tested with cisplatin (Platinol) in randomized trials, declared Claire F. Verschraegen, MD. The use of irinotecan might enable clinicians in developing countries (where radiotherapy equipment is in short supply) to downsize many cervical cancers to resectable size, Dr. Verschraegen added. She is assistant professor in the Division of Cancer Medicine Section of Gynecologic and Medical Therapeutics at the University of Texas M. D. Anderson Cancer Center in Houston, Texas.