Clinical Ovarian Cancer

Clinical Ovarian … & Other Gynecologic Cancer Too!

David M. Allen — 2011-12-01

Clinical Ovarian Cancer & Other Gynecologic Malignancies has always sought to evolve along with the interests of our readership. Since our debut in June 2008, we have striven to provide physicians and health care professionals with the information needed to effectively combat gynecologic malignancies. Our scope has remained unchanged since the launch of the journal: published debates on controversial topics in gynecologic oncology; review articles on the detection, diagnosis, prevention, and treatment of gynecologic cancers; original research articles focusing primarily on clinical and translational research in gynecologic cancer; and unique gynecologic cancer case reports.

PRO: Therapy for a Patient With Platinum–Resistant/Refractory Recurrent Ovarian Carcinoma Should be Selected Based on the Result of an In Vitro Chemoresistance Assay

J. Tate Thigpen — 2011-12-01

Ovarian cancers are the second most frequent group of invasive malignancies of the female genital tract (an estimated 21,650 new cases in 2008); however, the lack of an effective early diagnostic test for ovarian cancer results in ovarian cancers accounting for more deaths than the other 2 major gynecologic cancers combined (an estimated 15,520 deaths in 2008). Stage distribution at diagnosis explains the lethality of ovarian cancer because 75%-80% of cases present as stage III-IV (advanced) disease and require systemic therapy as the mainstay of treatment.

CON: Therapy for a Patient With Platinum–Resistant/Refractory Ovarian Cancer Should Not be Selected Based on Results of an In Vitro Extreme Drug Sensitivity/Resistance Assay

John Farley, Michael J. Birrer — 2011-12-01

Ovarian cancer remains an important health problem for women in the United States. It is estimated that there will be 21,650 cases of invasive ovarian cancer resulting in 15,520 deaths in 2008. Ovarian cancer has the highest case-fatality rate of all gynecologic cancers, and it is the most common cause of death from cancers of the female genital track. The high case-fatality rate results from the frequent diagnosis of epithelial ovarian cancer at an advanced stage: 75% of all cases are diagnosed as stage III or IV, in which the disease has spread throughout the abdomen. Patients with advanced-stage disease have a 5-year survival of only 29%. Epithelial ovarian cancer is initially a very chemoresponsive tumor with response rates of approximately 80%. Unfortunately, ≤ 75% of patients with advanced-stage disease will develop recurrent disease, which rapidly acquires chemoresistance, leading to death from the disease. The best strategy for selection of second-line chemotherapy after relapse in chemoresistant ovarian cancer has yet to be fully elucidated. Most commonly, patients are treated with a series of second- and third-line drugs that have been demonstrated to produce a modest response rate in this patient population. The precise selection of drug usually depends on a number of factors, including previous therapies, toxicities, patient wishes, and physician bias. Over the past 20 years, in vitro drug assays have been proposed as a solution to the accurate selection of a chemotherapeutic agent for patients with cancer. This article will address whether this is a rational approach to this selected platinum–refractory/resistant population.

PRO: Patients With Endometrial Carcinoma Involving Extrauterine Disease Should, After Any Indicated Surgery, Receive Chemotherapy

J. Tate Thigpen — 2011-12-01

Patients with endometrial carcinoma involving extrauterine disease should, after any indicated surgery, receive chemotherapy. The following discussion supports the pro side of this thesis. To determine whether this thesis is true and consistent with the current standard of care, several issues should be discussed: the general facts about endometrial carcinoma, the data favoring the use of chemotherapy in such patients, rational implications of the data, answers to counterarguments, and final conclusions.

CON: Not All Patients With Endometrial Cancer With Extrauterine Disease Should Receive Chemotherapy After Any Indicated Surgery

Marcus E. Randall — 2011-12-01

The adoption of primary surgical therapy and staging (including lymph node assessment and/or dissection) has given us a better understanding of prognostic groups, risk factors, and patterns of recurrence. Furthermore, the recognition of clear-cell and papillary carcinomas of the endometrium (PCE) as distinct subtypes of endometrial carcinoma has provided further information along these lines. Although clinicians now have, in many cases, a more complete understanding of disease extent and surgicopathologic features in an individual patient, the manner in which this information should affect the choice of adjuvant therapy is still debated.

PRO: Patients With Recurrent Ovarian Cancer Should be Treated With Antiangiogenic Agents in Combination With Chemotherapy

David Boruta, John Farley, Michael J. Birrer — 2011-12-01

Ovarian cancer remains a serious health problem for women in the United States. The American Cancer Society estimates that 21,650 women will be diagnosed with ovarian cancer in 2008.1 Of the 28,490 deaths expected from all gynecologic malignancies in 2008, over 50% (15,520 deaths) will be attributed to ovarian cancer, making it the most lethal gynecologic malignancy in the United States. Up to 75% of women with ovarian cancer are diagnosed with advanced-stage disease. Current treatment algorithms for newly diagnosed patients incorporate surgical cytoreduction and platinum/taxane–based chemotherapy. Despite initial response rates approximating 80%, the disease recurs in > 75% of women, and drug-resistant disease eventually develops. New approaches to the management of women with recurrent advanced ovarian cancer are desperately needed.

CON: Patients With Recurrent Ovarian Carcinoma Should Not be Treated With Antiangiogenic Agents in Combination With Chemotherapy

Paul Sabbatini — 2011-12-01

The following discussion argues against the assertion that patients with recurrent ovarian cancer should routinely receive anti-angiogenic agents in combination with chemotherapy. In order to support the premise that antiangiogenic agents should not yet be routinely used in all patients, we will consider the following items: (1) standard approaches for patients with recurrent disease; (2) the activity and toxicity of bevacizumab as the predominant representative agent in recurrent ovarian cancer; (3) ongoing phase III clinical trials; and (4) critical questions that remain to be answered.

PRO: Secondary Surgical Debulking is an Acceptable Option in Patients With Recurrent Platinum-Sensitive Ovarian Cancer

Christa I. Nagel, Matthew J. Carlson, Larry J. Copeland — 2011-12-01

While cytoreductive surgery and platinum-based chemotherapy remain mainstays of the primary treatment of epithelial ovarian cancer, > 60% of patients will be diagnosed with a recurrence. Despite the large number of patients who experience recurrences, the secondary treatment of choice varies widely.

CON: Secondary Surgical Debulking is Not an Acceptable Option in Patients With Recurrent Platinum-Sensitive Ovarian Cancer

J. Tate Thigpen — 2011-12-01

Cancer of the ovary is the eighth most common invasive malignancy of women and accounts for over half of the deaths related to gynecologic cancer the United States. Over 90% of these cases arise from celomic epithelium which invests the ovary during development and also lines the entire peritoneal cavity. The relatively high mortality rate results from the fact that these celomic epithelial carcinomas usually present at an advanced stage (FIGO stage III or IV). The current standard of care for women with advanced celomic epithelial carcinoma includes an aggressive attempt at surgical bulk reduction followed by chemotherapy consisting of paclitaxel plus carboplatin for 6 cycles. Such an approach produces a clinical complete response in 75% of women with advanced disease, 95% in those who start chemotherapy with small-volume residual disease (no nodule larger than 1 cm remaining after surgical bulk reduction) and 50% in those with large-volume residual disease.

PRO: Patients at High Risk for Ovarian Cancer Should Undergo Routine Screening

Beth Y. Karlan — 2011-12-01

Ovarian cancer remains the most lethal of all the gynecologic cancers. This is due in large part to the stage distribution of ovarian cancer. At the current time, over two thirds of patients have late-stage metastatic disease at the time of initial diagnosis. Early detection is a primary objective because of its promise for improved survival and quality of life. Five-year survival is > 90% when ovarian cancer is diagnosed at stage I and still confined to the ovaries. However, < 25% of cases are detected at stage I. For the vast majority of women, the disease remains undetected until it is already widely metastatic. In these cases, the survival rate has remained around 30% for many decades despite aggressive surgery and aggressive chemotherapy. If even half of the stage III and IV cases of ovarian cancer could be detected while they are still confined to the ovary, we could significantly improve the overall survival for this disease.

CON: Patients at High Risk for Ovarian Cancer Should Not Undergo Routine Screening

Thomas P. McNally, Michael J. Birrer — 2011-12-01

Ovarian cancer represents a significant and continuing health problem among women. For 2009, the American Cancer Society estimates that 21,550 women in the United States will have been newly diagnosed with ovarian cancer, with 14,600 deaths attributable to the disease. Ovarian cancer is the second most common gynecologic cancer but accounts for 55% of all deaths associated with gynecologic malignancies. This high case-fatality rate is directly attributable to the late stage at which most ovarian cancers are diagnosed. Only 15% of all ovarian cancers are diagnosed at stage I, with the tumor confined to the ovary, whereas 79% are diagnosed at stages II, II, and IV and have already spread to the surrounding tissues. When one considers the 5-year survival rates of 93.8% for stage I and only 28.2% for stages II, III, and IV, the true threat from this disease becomes apparent.

PRO: Patients With Metastatic/Recurrent Cervical Cancer Should be Treated With Cisplatin Plus Paclitaxel

Krishnansu S. Tewari — 2011-12-01

Invasive cervical cancer was once one of the most common malignancies to affect women in the United States. Although it remains a worldwide epidemic with greater than 500,000 new cases diagnosed annually, resulting in 250,000 deaths each year, the incidence of the disease in developed countries has decreased over the preceding 60 years. In 2009, it was estimated that there were 11,270 new cases of invasive cervical cancer and approximately 4070 deaths. The vast majority of these deaths occur among patients with untreated locally advanced and metastatic disease as well as those whose disease recurs after definitive therapy for locally advanced lesions.

CON: Patients With Metastatic/Recurrent Cervical Cancer Should Not be Treated With Cisplatin Plus Paclitaxel

J. Tate Thigpen — 2011-12-01

The success of assessment of cervical cytology as a screening test for carcinoma of the uterine cervix has markedly reduced the number of deaths caused by this cancer in developed countries such as the United States. In 2009 in the United States, the number of invasive cases was estimated to be 11,270, and the number of deaths was estimated to be 4070. Such is not the case in less well developed countries, in which carcinoma of the uterine cervix still is the most common cause of death related to gynecologic cancer. Most deaths relate to recurrent disease after initial treatment of earlier-stage disease with either surgery or concurrent chemoradiation. Although highly selected patients can be treated successfully with surgery and/or radiation in the recurrent-disease setting, the mainstay of therapy for the vast majority of patients with recurrent carcinoma of the cervix will be systemic therapy in the form of chemotherapy. This debate, whether or not patients with recurrent cervical cancer should be treated with cisplatin/paclitaxel, focuses on what constitutes the optimal systemic therapy for these patients with recurrent disease. In the great spirit of the debate, this side could take the position that not all patients with recurrent disease should be treated with chemotherapy and that selected patients may be candidates for surgery with potentially curative results. Instead, this article will point to solid reasons for not treating most patients with paclitaxel/cisplatin.

PRO: Systemic Therapy for All Endometrial Cancers Should be Paclitaxel Plus Carboplatin

Matthew A. Powell — 2011-12-01

The American Cancer Society estimates that approximately 1 in 40 women in the United States will develop uterine cancer during their lifetime. The majority of the patients diagnosed with endometrial carcinoma will present with early-stage cancers. They are usually cured with appropriate surgical therapy. The most appropriate therapy for patients determined to be at intermediate and high risk for recurrence of their cancer remains unknown. Traditionally, these patients have been treated with adjuvant pelvic external-beam radiation therapy (PEBRT). Multiple randomized trials have evaluated this treatment modality and have not demonstrated convincing improvements in patient survival. Cytotoxic chemotherapy had been, until only recently, used in patients with advanced or recurrent endometrial cancer not amendable to or only following the use of radiation therapy. The Gynecologic Oncology Group (GOG) has over the past several decades undertaken a rational evaluation of both multiple single agents and combinations of chemotherapy regimens in patients with advanced stage and recurrent disease. These patients typically all have had measurable disease as criteria for entry to the trials. GOG 177 demonstrated the combination of paclitaxel, doxorubicin, and cisplatin (PDC) to be superior to doxorubicin and cisplatin (DC) alone. Unfortunately, even with this most aggressive therapy, responses are usually only partial and are of a relatively short duration, with most patients ultimately dying of their disease. Thus, chemotherapy in this setting is largely palliative, with a modest impact on survival. The trend in therapy development has been to focus on patients at an intermediate and high risk for relapse and to intervene with adjuvant systemic therapy when the chance for cure is hopefully improved.

CON: Systemic Therapy for All Endometrial Carcinomas Should Not be Paclitaxel Plus Carboplatin

J. Tate Thigpen — 2011-12-01

The thesis of the pro side of this debate is that systemic therapy for all endometrial carcinomas should be paclitaxel/carboplatin. To determine whether this thesis is true and is consistent with the current standard of care, several issues should be discussed: (1) facts about endometrial carcinoma that affect the decision to use systemic therapy, (2) data favoring the use of chemotherapy in such patients, (3) rational implications of the data, (4) answers to counterarguments, and (5) final conclusions.

PRO: All Patients With Serous and Clear Cell Carcinomas of the Endometrium Should Receive Chemotherapy as Part of Their Treatment

Todd P. Boren, David S. Miller — 2011-12-01

Uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC) represent 2 rare endometrial cancer subtypes with significantly worse outcomes than the more common endometrioid endometrial cancer (EEC) subtype. Homogeneous prospective data are lacking that inform upon optimal treatment strategies for these cancers. Phase III chemotherapy trials in advanced-stage disease that include UPSC and UCCC as well as retrospective and phase II trials specifically addressing the role of chemotherapy in advanced-stage UPSC and UCCC suggest that all of these patients should receive adjuvant platinum- and taxane-based chemotherapy. There are no completed prospective trials addressing chemotherapy in early-stage UPSC and UCCC and retrospective data alone have driven treatment recommendations for these tumors. Given the tendency of UPSC and UCCC to recur distally, the low salvage rates observed after recurrence, and the survival benefit associated with adjuvant chemotherapy, the available retrospective data suggest that all patients with early-stage UPSC and UCCC should receive platinum- and taxane-based chemotherapy as part of the adjuvant treatment plan.

CON: Not All Patients With Serous and Clear Cell Carcinomas of the Endometrium Should Receive Chemotherapy as Part of Their Treatment

Eric L. Eisenhauer — 2011-12-01

Although endometrial cancer is the most common gynecologic malignancy among women in the United States, serous and clear cell carcinomas are less common and more virulent histologic types. Uterine papillary serous carcinoma (UPSC) accounts for < 10% of new endometrial cancers, but almost 40% of subsequent deaths. Uterine clear cell carcinoma represents only 3% of new cases, but 8% of deaths. The relative incidence of both of these type II endometrial cancers appears to be increasing.

Editorial Board

2011-12-01

Clinical Ovarian Cancer

Clinical Ovarian … & Other Gynecologic Cancer Too!

PRO: Therapy for a Patient With Platinum–Resistant/Refractory Recurrent Ovarian Carcinoma Should be Selected Based on the Result of an In Vitro Chemoresistance Assay

CON: Therapy for a Patient With Platinum–Resistant/Refractory Ovarian Cancer Should Not be Selected Based on Results of an In Vitro Extreme Drug Sensitivity/Resistance Assay

PRO: Patients With Endometrial Carcinoma Involving Extrauterine Disease Should, After Any Indicated Surgery, Receive Chemotherapy

CON: Not All Patients With Endometrial Cancer With Extrauterine Disease Should Receive Chemotherapy After Any Indicated Surgery

PRO: Patients With Recurrent Ovarian Cancer Should be Treated With Antiangiogenic Agents in Combination With Chemotherapy

CON: Patients With Recurrent Ovarian Carcinoma Should Not be Treated With Antiangiogenic Agents in Combination With Chemotherapy

PRO: Secondary Surgical Debulking is an Acceptable Option in Patients With Recurrent Platinum-Sensitive Ovarian Cancer

CON: Secondary Surgical Debulking is Not an Acceptable Option in Patients With Recurrent Platinum-Sensitive Ovarian Cancer

PRO: Patients at High Risk for Ovarian Cancer Should Undergo Routine Screening

CON: Patients at High Risk for Ovarian Cancer Should Not Undergo Routine Screening

PRO: Patients With Metastatic/Recurrent Cervical Cancer Should be Treated With Cisplatin Plus Paclitaxel

CON: Patients With Metastatic/Recurrent Cervical Cancer Should Not be Treated With Cisplatin Plus Paclitaxel

PRO: Systemic Therapy for All Endometrial Cancers Should be Paclitaxel Plus Carboplatin

CON: Systemic Therapy for All Endometrial Carcinomas Should Not be Paclitaxel Plus Carboplatin

PRO: All Patients With Serous and Clear Cell Carcinomas of the Endometrium Should Receive Chemotherapy as Part of Their Treatment

CON: Not All Patients With Serous and Clear Cell Carcinomas of the Endometrium Should Receive Chemotherapy as Part of Their Treatment

Editorial Board

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