Feasibility of laparoscopic management of presumed stage I endometrial carcinoma and assessment of accuracy of myoinvasion estimates by frozen section: a gynecologic oncology group study.

INTRODUCTION: To assess laparoscopic management of presumed stage I endometrial cancer, and to compare gross, frozen, and paraffin section methods measuring myoinvasion. PATIENTS AND METHODS: Eligible patients underwent laparoscopic exploration. Patients with preoperative grade 1 histology underwent laparoscopic-assisted vaginal hysterectomy and bilateral salpingo-oophorectomy (LAVHBSO). Pelvic and periaortic lymph node sampling (PPANS) was performed for deep (> or =50%) myoinvasion confirmed by frozen section. Patients with preoperative grade 2 or 3 histology without evidence of extrauterine metastasis underwent PPANS + LAVHBSO. RESULTS: Of 50 eligible patients selected, LAVHBSO was successfully completed in all but five. There was one trocar bowel perforation. Myoinvasion depth was correlated between paraffin section and gross estimate, and between paraffin and frozen section estimate, in 89 and 90% of cases, respectively. Myoinvasion was underestimated by gross versus paraffin in three of five discrepancies, and by frozen versus paraffin section in one of three discrepancies. CONCLUSIONS: Laparoscopic surgical staging for early stage endometrial cancer is feasible. Gross/frozen section methods correlate with paraffin section to measure myoinvasion. Tumor grading and gross/frozen section myoinvasion estimates can guide operative management.

A dose-escalating study of weekly bolus topotecan in previously treated ovarian cancer patients.

OBJECTIVE: Topotecan is an established topoisomerase I inhibitor for the treatment of relapsed ovarian cancer. Myelotoxicity and suboptimal patient convenience associated with daily topotecan, however, have prompted investigators to explore alternate regimens, including a weekly regimen of topotecan. The objective of this study was to determine the maximum tolerated dose (MTD) of topotecan given as a weekly bolus in previously treated ovarian cancer patients. METHODS: Second- and third-line ovarian cancer patients with measurable disease or elevated cancer antigen 125 received weekly bolus topotecan intravenously starting at 1.5 mg/m(2). Topotecan was escalated in dose increments of 0.5 mg/m(2) every 21 days as tolerability allowed. Dose-limiting toxicity was defined as grade 3/4 neutropenia or thrombocytopenia. RESULTS: Thirty-two of 35 patients were evaluable for safety and tolerability. No notable toxicity was observed with weekly topotecan doses < 4 mg/m(2). Additionally, there was an absence of dose-limiting myelotoxicity and thrombocytopenia with weekly topotecan. The MTD of weekly topotecan without the use of granulocyte colony-stimulating factor support was 4 mg/m(2), with grade 2 anemia, chronic fatigue, and grade 2 gastrointestinal toxicity limiting further dose escalation. Weekly topotecan also demonstrated antitumor activity at doses >2 mg/m(2). CONCLUSIONS: The establishment of a well-tolerated, weekly regimen of topotecan (4 mg/m(2), with a maximum recommended dose of 6 mg/m(2)) provides the basis for further investigation in phase II studies of single-agent and combination regimens in previously treated ovarian cancer patients.

Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study.

PURPOSE: In two large Gynecologic Oncology Group studies of patients with advanced or recurrent endometrial carcinoma and no previous systemic therapy, progestins have demonstrated activity against advanced or recurrent endometrial carcinoma with response rates between 15% and 25%. Tamoxifen has been reported as variously active or inactive with or without previous systemic therapy. The purpose of this study was to determine whether tamoxifen exhibits enough activity in patients with advanced or recurrent endometrial carcinoma, who have not received systemic therapy, to warrant a phase III trial. PATIENTS AND METHODS: Sixty-eight eligible patients with advanced or recurrent endometrial carcinoma received oral tamoxifen 20 mg bid until toxicity was unacceptable or disease progressed. RESULTS: Three complete (4%) and four partial (6%) responses were observed for an overall response rate of 10% (90% confidence interval [CI], 5.7% to 17.9%). Patients with tumors that were more anaplastic tended to respond less frequently. The median progression-free survival for all 68 eligible patients was 1.9 months (90% CI, 1.7 to 3.2 months). The median survival was 8.8 months (90% CI, 7.0 to 10.1 months). CONCLUSION: Tamoxifen demonstrated modest activity at best against endometrial carcinoma and does not warrant further investigation as a single agent for this disease. Ongoing trials will assess the sequential use of tamoxifen and progestational agents.

Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group.

PURPOSE: Progestins have definite activity against advanced or recurrent endometrial carcinoma. Both parenteral and oral progestins yield similar serum levels and response rates, which range from 18% to 34%. The one major study that used oral medroxyprogesterone acetate (MPA) noted a response rate at the lower end of the range (18%) and much poorer progression-free and overall survival times (4 and 10.5 months, respectively) than previously reported. The present study sought to confirm this earlier study of oral MPA, to assess the importance of prognostic factors such as histologic grade and receptor levels, and to determine whether a higher dose of MPA would yield a higher response rate. PATIENTS AND METHODS: Two hundred ninety-nine eligible women with advanced or recurrent endometrial carcinoma were randomized to receive oral MPA either 200 mg/d or 1, 000 mg/d until unacceptable toxicity intervened or their disease progressed. RESULTS: Among 145 patients receiving the low-dose regimen, there were 25 complete (17%) and 11 partial (8%) responses for an overall response rate of 25%. The 154 patients receiving the high-dose regimen experienced 14 (9%) complete and 10 (6%) partial responses for an overall response rate of 15%. Median durations of progression-free survival were 3.2 months and 2.5 months for the low-dose and high-dose regimens, respectively. Median survival durations were 11.1 months and 7.0 months, respectively. The adjusted relative odds of responding to the high-dose regimen compared with the low-dose regimen was 0.61 (90% confidence interval, 0.36 to 1.04). Prognostic factors having a significant impact on the probability of response included initial performance status, age, histologic grade, and progesterone receptor concentration. Compliance with oral therapy was documented with serum levels 1 month after starting therapy, when possible. MPA levels were commensurate with the assigned dose and schedule. CONCLUSION: Oral MPA is active against endometrial carcinoma. Response to progestin therapy is more frequent among patients with a well-differentiated histology and positive progesterone receptor status. This study provides no evidence to support the use of MPA 1,000 mg/d orally instead of MPA 200 mg/d orally. In fact, the trends suggest the opposite. The use of oral MPA 200 mg/d is a reasonable initial approach to the treatment of advanced or recurrent endometrial carcinoma, particularly those lesions that are well-differentiated and/or progesterone receptor-positive (> 50 fmol/mg cytosol protein). Patients with poorly differentiated and/or progesterone receptor levels less than 50 fmol/mg cytosol protein had only an 8% to 9% response rate.

Bleomycin, etoposide, and cisplatin combination therapy of ovarian granulosa cell tumors and other stromal malignancies: A Gynecologic Oncology Group study.

OBJECTIVES: The objectives of this study were to assess efficacy and toxicity of the combination of bleomycin, etoposide, and cisplatin (BEP) in this Phase II trial as first-line therapy for ovarian stromal malignancies. METHODS: Patients with incompletely resected Stages II-IV or recurrent cancer underwent surgical debulking. There were two bleomycin-related deaths early in the trial; thus, the initial schedule of bleomycin (20 units/m2 x 9 weeks for a maximum dose of

Phase II trial of vinorelbine in recurrent and progressive epithelial ovarian cancer.

OBJECTIVE: A phase II, multicenter trial was conducted to define the efficacy and safety of vinorelbine (Navelbine (vinorelbine tartrate) injection, NVB) in the treatment of advanced epithelial ovarian cancer (EOC). METHODS: Patients with persistent or recurrent EOC who had received one prior platinum-based chemotherapy regimen were eligible. NVB was administered at 30 mg/m2 as a weekly outpatient intravenous infusion. RESULTS: Using an intent-to-treat analysis of the 38 patients who received at least one dose, 11(29%, 95% confidence limits 15-46%) objective responses (4 complete, 7 partial) were observed. The median duration of response was 19 weeks. For all 38 patients, the median time to treatment failure and median survival were 12 and 60 weeks, respectively. Four of the 12 patients with platinum-resistant disease responded, while 7 of the 24 patients with platinum-sensitive disease responded. Toxicity was evaluable in all 38 patients. During course 1, 15 patients required dose reduction and 21 required dose delays. Grade 3-4 granulocytopenia occurred in 23 (62%) of 37 reporting patients. Grade 3-4 anemia and thrombocytopenia occurred in 16 and 5%, respectively. The most common nonhematologic toxicities were nausea (grade 3 or less, in 34%), constipation (grade 3 or less, in 29%), and asthenia (grade 2 or less, in 24%). No life-threatening adverse effects were reported. CONCLUSIONS: NVB is an effective, palliative agent for women with recurrent EOC. Dose-limiting granulocytopenia is substantial, yet manageable.

Tomudex (ZD1694, NSC 639186) in platinum-pretreated recurrent epithelial ovarian cancer: a phase II study by the Gynecologic Oncology Group.

PURPOSE: Tomudex is a second-generation folate analogue that when polyglutamated is a potent inhibitor of thymidylate synthase (TS). METHODS: Based on indications of antitumor activity in phase I trials, the Gynecologic Oncology Group initiated a phase II study of Tomudex 3 mg/m2 intravenously every 3 weeks in patients with epithelial ovarian cancer, who had been pretreated with platinum drugs, and had subsequently recurred more than 6 months following such treatment. RESULTS: Of 30 patients entered into the trial, 2 were pathologically ineligible, leaving 28 fully evaluable. In this patient population, Tomudex was generally well tolerated, but only three objective (partial) responses were documented. CONCLUSIONS: With the level of activity seen, the drug was not considered for further clinical development in ovarian cancer by the Gynecologic Oncology Group. However, it may be worthwhile to explore whether quantitation of TS could lead to selection of patients more likely to respond to this TS inhibitor.

Gynecologic problems in older women.

Regular gynecologic evaluation in older women is an integral part of medical care, just as it is for women of reproductive age. This should be emphasized since older women often neglect early symptoms of gynecologic diseases, some of which are potentially lethal. With this in mind, the health care provider must be cognizant of not only gynecologic problems that affect all women, but also those disease processes which are either specific to or more prevalent in an older population. This article emphasizes these aspects in caring for the older gynecologic patient.

Single-agent therapy for nonmetastatic and low-risk gestational trophoblastic disease.

OBJECTIVE: To assess the effectiveness of single-agent chemotherapy in the treatment of nonmetastatic and low-risk metastatic gestational trophoblastic tumors. STUDY DESIGN: The medical literature was reviewed concerning single-agent chemotherapy in the treatment of nonmetastatic and low-risk metastatic gestational trophoblastic tumors. RESULTS: Methotrexate and actinomycin-D have achieved excellent and comparable remission rates with acceptable levels of toxicity. CONCLUSION: The optimal single-agent chemotherapy for nonmetastatic and low-risk metastatic gestational trophoblastic tumors has not yet been identified and can be best determined through a prospective, randomized trial.

Early invasive carcinoma of the cervix (3 to 5 mm invasion): risk factors and prognosis. A Gynecologic Oncology Group study.

OBJECTIVE: Our purpose was to evaluate the risk factors and prognosis in patients with stage IA squamous cell carcinoma of the cervix and 3 to 5 mm of invasion. STUDY DESIGN: From 1981 to 1984 the Gynecologic Oncology Group conducted a prospective clinicopathologic study of patients with stage I carcinoma of the cervix. A selective study group that was previously defined and reported included patients with squamous cell carcinoma of the cervix who were treated with radical hysterectomy and pelvic lymphadenectomy and who had disease confined to the uterus, with or without microscopically positive lymph nodes. RESULTS: One hundred eighty-eight patients had invasion of 3, 4, or 5 mm as determined by central pathology review. Patients who satisfied the 3 to 5 mm invasion definition of the current stage IA2 classification of the International Federation of Gynecology and Obstetrics (1995) are the subject of this report. CONCLUSIONS: Patients with stage IA2 carcinoma of the cervix who have 3 to 5 mm of invasion present on conization with no invasion in the hysterectomy specimen are at very low risk for lymph node metastases, recurrences, or death caused by cancer.

Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study.

PURPOSE: A phase II trial was conducted to determine the activity of prolonged oral etoposide in platinum-resistant and platinum-sensitive ovarian carcinoma. PATIENTS AND METHODS: Platinum-resistant disease was defined as progression on platinum-based chemotherapy or recurrence within 6 months of completing therapy. The starting dose was 50 mg/m2/d (30 mg/m2/d for prior radiotherapy) for 21 days, every 28 days. A dose escalation to a maximum dose of 60 mg/m2/d was prescribed. RESULTS: Of 99 patients entered, 97 were assessable for toxicity and 82 were assessable for response. Among 41 platinum-resistant patients a 26.8% response rate (7.3% complete response [CR] and 19.5% partial response [PR] rate) occurred. The median response duration was 4.3 months (range, 1.3 to 8.7), median progression-free interval (PFI) was 5.7 months (range, 0.8 to 30.8+), and median survival time was 10.8 months (range, 1.9 to 45.8). Twenty-five of 41 platinum-resistant patients had also previously received paclitaxel; of which eight (32%) responded. Among 41 platinum-sensitive patients, a 34.1% response rate (14.6% CR and 19.5% PR rate) occurred. The median response duration was 7.5 months (range, 1.9 to 15.2+), median PFI was 6.3+ months (range, 0.9 to 20.4), and median survival time was 16.5+ months (range, 0.9 to 34.8). Of 97 patients assessable for toxicity, grade 3 or 4 hematologic toxicity was common, with leukopenia occurring in 41.2% (grade 3, 29%; grade 4, 12%), neutropenia in 45.4% (grade 3, 20%; grade 4, 25%), thrombocytopenia in 9% (grade 3, 5%; grade 4, 4%), and anemia in 13.4%. Three treatment-related deaths occurred: two from neutropenic sepsis and one from thrombocytopenic bleeding after an overdose. One patient developed leukemia. CONCLUSION: This regimen is active in platinum-resistant and platinum-sensitive ovarian carcinoma. Additionally, the regimen is active in paclitaxel-resistant ovarian carcinoma.

A phase I study of weekly cisplatin and whole abdominal radiation for the treatment of stage III and IV endometrial carcinoma: a Gynecologic Oncology Group pilot study.

A Gynecologic Oncology Group Phase I study was designed to evaluate the toxicity of whole abdominal radiation therapy with concurrent weekly cisplatin in patients with surgical International Federation of Gynaecology and Obstetrics (FIGO) Stage III and IV endometrial carcinoma. Cisplatin 15 mg/m2 was given once weekly during radiation therapy to the whole abdomen with a pelvic boost and optional para-aortic radiation. All eight patients received the prescribed dose of radiation therapy. Cisplatin chemotherapy was halted in one patient due to increased serum creatinine after three cycles. Acute adverse effects were within acceptable limits, with one patient admitted to the hospital after completion of treatment for diarrhea. Hematopoietic toxicity was clinically unimportant. Serious late toxicities included one radiation enteritis requiring a bowel resection and chylous ascites in one patient. There was no late renal damage reported. This regimen appears to be tolerated acutely and the late toxicities were similar to those seen with whole abdominal radiation therapy alone.

An analysis of cell type in patients with surgically staged stage IB carcinoma of the cervix: a Gynecologic Oncology Group study.

The influence of cell type on recurrence-free interval (RFI) and survival after radical hysterectomy for patients with Stage IB carcinoma of the cervix was investigated. Patients with Stage IB carcinoma of the cervix (>3-mm invasion) underwent a radical hysterectomy and pelvic lymphadenectomy. Patients with involved paraaortic nodes or gross extracervical disease were excluded. Of 813 evaluable patients, 645 had squamous, 104 with adenocarcinoma, and 64 had adenosquamous cell type. The time to failure and the following clinical/pathologic characteristics were compared among the three cell types: age, Gynecologic Oncology Group performance status (PS), gross versus occult tumor, histologic grade, depth of invasion, node status, uterine extension, parametrial extension, surgical margins, and capillary-lymphatic space (CLS) involvement. A Cox proportional hazards model was used to compare the patients with adenosquamous and adenocarcinoma to those with squamous while adjusting for prognostic factors. The median age was 40 years (range, 21-87). Pelvic nodes were involved in 119 (15%) of patients. There were no significant differences between cell types in distributions of the following factors: age, PS, positive nodes, depth of invasion, uterine extension, surgical margins, or parametrial extension. There were statistically significant differences between cell types with regards to grade (P < 0.001), gross versus occult primary status (P = 0.016), and CLS involvement (P = 0.005). There was no statistically significant difference detected between cell types in crude comparisons of RFI (P = 0.29); however, there was a difference in survival (P = 0.02) with shorter survival seen in the adenosquamous cell type. After adjusting for CLS involvement, PS, depth of invasion, and clinical tumor size, survival remained worse for patients with adenosquamous primaries when compared to squamous carcinoma (P = 0.02) and adenocarcinoma (P = 0.007). In conclusion, no statistically significant differences were seen in RFI among cell types; however, in patients with Stage I carcinoma of the cervix overall survival after radical hysterectomy may be slightly worse for those with adenosquamous cell type.

Are more antiemetic trials with a placebo necessary? Report of patient data from randomized trials of placebo antiemetics with cisplatin.

BACKGROUND: Because of the predictability of significant emesis after its use, cisplatin serves as the standard emetic stimulus for trials of antiemetic drugs. To define better the incidence, severity, and pattern of emesis that follows cisplatin, facilitate the testing of new agents, and obviate the need for further placebo-controlled trials for this indication, individual patient data were compiled from completed studies with placebo antiemetics and cisplatin. METHODS: The time and number of emetic episodes during the 24 hours after cisplatin were obtained for 48 patients given a placebo antiemetic. Each was treated as part of a randomized, double-blind trial reported between 1981 and 1990. Emesis after antiemetic "rescue" therapy was also assessed. RESULTS: Emesis occurred in 47 of 48 patients (98% observed rate, 95% confidence interval, 89-99%). The median number of emetic episodes during the 24 hours after cisplatin was 6. Emesis continued after rescue in 77% of patients. CONCLUSIONS: Cisplatin caused severe emesis that persisted despite rescue in placebo-treated patients. Using the data presented, any therapy preventing acute emesis in 8 or more of the 48 individuals receiving cisplatin > 50 mg/m2 was an active antiemetic (P = 0.05). The four trials discussed here documented the antiemetic effectiveness of granisetron, metoclopramide, and ondansetron. The placebo-treated patients studied can serve as a control group for testing new therapies. Because of the certainty of severe emesis after cisplatin, and the availability both of these data and several proven drugs for this condition, prospective comparisons of antiemetics should employ active control medications.

A phase II trial of didemnin B (NSC #335319) in patients with advanced squamous cell carcinoma of the cervix. A Gynecologic Oncology Group Study.

Didemnin B (NSC #335319) was administered i.v. to 26 evaluable patients with advanced, persistent, or recurrent squamous cell carcinoma of the cervix at 6.3 mg/m(2) every 28 days until progression of disease. No patient had had prior cytotoxic therapy alone. Some patients (4) were exposed to radiation sensitizers. There was one complete responder (4.5%). Six patients had stable disease (27.3%) and 15 (68.2%) had increasing disease. The toxicities were significant, with 11 patients (42.3%) experiencing grade 3 or 4 adverse effects. Didemnin B, when used with this dose and schedule, has minimal activity in squamous cell carcinoma of the cervix.

Management of endometrial cancer.

Preoperative assessment requires only endometrial sampling for diagnosis. Curettage is needed when endometrial sampling is unsatisfactory. Transvaginal ultrasonography may be useful in screening high-risk patients, as well as in assessing myoinvasion or cervical extension. Postsurgical pathologic prognostic factor analysis is most accurate in assigning risk for recurrence. Once the extent of disease is confirmed by the surgical staging procedure of hysterectomy, bilateral removal of the ovaries, and selective pelvic and periaortic node dissection, adjunctive therapy can be considered. Patients with low-risk stage IA and IB grade 1 disease require hysterectomy and removal of the adnexa. The poorer prognosis of patients with grade 2 or 3 histologic features in stages IB to IIB dictates considerations for adjunctive therapy. Soon randomized controlled trials will elucidate objectively what may be optimal adjunctive therapy. Ongoing prospective trials will clarify the role of operative laparoscopy. Current management guidelines are based on independent prognostic factors derived from analysis of surgicopathologic studies.

Chemotherapy, early surgical reassessment, and hyperfractionated abdominal radiotherapy in stage III ovarian cancer: results of a gynecologic oncology group study.

PURPOSE: To determine outcomes and treatment toxicities in patients with optimal (< or = 1 cm residual) Stage III ovarian carcinoma treated with three courses of cisplatin-cyclophosphamide, surgical reassessment (SRA), and hyperfractionated whole abdominal irradiation (WAI). METHODS AND MATERIALS: Forty-two eligible patients entered this prospective Phase II study conducted by the Gynecologic Oncology Group (GOG). Disease characteristics were as follows: age range, 32-76 years (median 58); Stage IIIA (n = 1, 2%), IIIB (n = 2, 5%), IIIC (n = 39, 93%); histology-serous papillary (n = 21, 50%); other (n = 21, 50%); Grade 1 (n = 1, 2%); 2 (n = 14, 33%); 3 (n = 27, 54%); residual disease after initial surgery (present: n = 23, 55%; absent: n = 19, 45%). Five patients progressed while on chemotherapy, could not be effectively cytoreduced, and were not eligible for WAI. Of the remaining 37 patients, 35 received WAI. Surgical reassessment was not performed in five patients. RESULTS: Of 37 patients with known SRA status after chemotherapy, 21 (57%) were grossly positive, 4 (11%) were microscopically positive, and 12 (32%) were negative. Based on measurements recorded following initial laparotomy and surgical reassessment, progression during chemotherapy was noted in 40%, stage disease in 37%, and objective response in 23%. Toxicity during hyperfractionated WAI was limited and reversible. No patient beginning WAI failed to complete or required a significant treatment break. Following WAI, six patients underwent laparotomies for abdominal symptoms; five had recurrent disease. Five additional patients were managed conservatively for small bowel obstruction (SBO) or malabsorption, of whom three subsequently developed recurrence. Twenty-two patients having pelvic boosts were significantly more likely to require management for gastrointestinal morbidity (p = 0.0021). Considering all eligible patients, median disease-free and overall survivals were 18.5 and 39 months, respectively. Considering patients completing chemotherapy and WAI, median disease-free and overall survivals were 24 and 46 months, respectively. CONCLUSIONS: (a) Disease progression occurred within three cycles of cisplatin and cyclophosphamide chemotherapy in 40% of patients with optimal (< or = 1 cm residual) Stage III ovarian carcinoma. (b) Following limited chemotherapy, hyper-fractionated WAI was acutely well tolerated. (c) Late radiation-related toxicity was observed in only three patients (8.6%) in the absence of recurrent disease. Late gastrointestinal morbidity was significantly associated with the administration of a pelvic radiotherapy (RT) boost. (d) Short duration chemotherapy followed by SRA and hyperfractionated WAI without a pelvic boost is a promising management option for patients with optimal Stage III ovarian cancer. A Phase III trial will be necessary to determine how this treatment strategy compares with chemotherapy or RT alone in this patient population.

A phase II trial of gallium nitrate (NSC #15200) in nonsquamous cell carcinoma of the cervix. A Gynecologic Oncology Group study.

A Phase II trial of gallium nitrate for patients with recurrent or metastatic nonsquamous cell carcinoma of the cervix was conducted by the Gynecologic Oncology Group (GOG) from March 1988 to January 1992. Twenty-six evaluable patients were treated with 750 mg/m2 of gallium nitrate every 3 weeks. Age range was 30-74 years with a median of 48 years. GOG performance status was 0-1 for all but four patients. Two patients had a complete response (7.7%), 1 patient had a partial response (3.8%), 13 patients had stable disease (50.0%), and 10 (38.5%) had increasing disease. The 95% confidence interval for response is 2.4-30.2%. The major toxicities were nausea, vomiting, and anemia. Gallium nitrate has modest activity in patients with nonsquamous cell carcinoma of the cervix.

Management of vulvar cancer.

BACKGROUND: Current therapy of vulvar malignancies is reviewed with emphasis on screening, etiology, diagnosis, staging, and treatment of preinvasive and invasive cancer. METHODS: Screening procedures, etiologic possibilities, diagnostic techniques, staging implications, and treatment approaches are discussed in detail. RESULTS: All malignancies of the vulva should be detected at an early stage, when they are most amenable to curative therapy. Regular examination of all women and increased efforts to educate patients should in time reduce patient and physician delay in diagnosis. The cause of the disease remains unclear, because the precursor state has not been defined accurately. The impetus to perform more conservative surgery has been accompanied by the realization of the severe psychosexual sequelae associated with radical vulvectomy. High risk prognostic factors include number of positive groin lymph nodes and diameter of the primary lesion. Diameter of the largest metastasis, intracapsular versus extracapsular nodal tumor location, laterality of spread, and deep groin nodal spread may be predictors of survival. CONCLUSIONS: The overall incidence of vulvar malignancies will not be changed until the pathophysiology of the disease is better understood. Improved survival will depend on earlier and more accurate diagnosis and treatment, including use of radiation therapy.

Radiation-induced vesicosacral fistula: treatment with continent urinary diversion.

This is the first Case Report of a vesicosacral fistula related to prior radiation therapy. This patient developed recurrent adenosquamous carcinoma of the cervix 1 year after radical hysterectomy. She received 5000 cGy to the whole pelvis and a 1500-cGy boost to the area of recurrence in the right pelvic sidewall. The patient had significant toxicity with recurrent pelvic fistula formation ultimately requiring an end sigmoid colostomy. In addition, the patient required urethral catheterization due to urinary incontinence secondary to a hypertonic bladder. Approximately 14 years after radiation therapy the patient developed a vesicosacral fistula. With a nonfunctional bladder, the decision was made to proceed with a continent urinary diversion procedure. Despite a prior ileocecal resection due to radiation injury, a Miami pouch reservoir was created. Postoperatively, the patient remained continent using intermittent catheterization of the pouch.