Long-term survival with advanced ovarian cancer: an analysis of 5-year survivors in the Australian trial comparing combination versus sequential chlorambucil and cisplatin therapy.

Of 369 patients with apparent advanced ovarian cancer entered on a randomized trial between September 1979 and June 1983, 56 survived more than 5 years. Central pathology review confirmed the diagnosis in 318 cases (15 cases not ovarian primary, 36 slides did not reach central review). Two hundred ninety-eight were invasive cancer and 34 of these (11.4%) patients were alive at 5 years. The remaining 20 cases were tumors of low malignant potential and 17 (85%) were alive at 5 years. The clinical, pathological, and treatment characteristics of these long-term survivors has been ascertained. No significant difference in survival has emerged between the two treatment arms being compared--combination chlorambucil and cisplatin versus sequential chlorambucil followed by cisplatin on treatment failure. Of 298 cases of invasive cancer there were 133 with residuum less than 2 cm after initial surgery and 20 of these (15%) survived 5 years compared with 14/165 (8.5%) of those with more tumor residuum. Clinical response was a poor indicator of survival. Only 7 of 46 (15%) patients with complete clinical response survived 5 years; however, of 44 patients with complete surgical response, 29 (65.9%) were alive at 5 years. These results highlight the improved survival prospects of women with low-potential malignancy, even in advanced stage, compared to those with invasive tumors and make a strong case for central pathology review of all cases of apparent ovarian cancer entered on randomized trials.

Extraovarian peritoneal serous papillary carcinoma. A clinicopathologic study of 31 cases.

The rate and clinical features of patients admitted to King George V Hospital with extraovarian peritoneal serous papillary carcinoma during a 9-year period were reviewed. In this time, 31 of 236 (13%) patients with an initial diagnosis of invasive serous ovarian carcinoma fulfilled the surgicopathologic criteria for this entity. All patients had disseminated tumor equivalent to ovarian Stage III and IV disease (International Federation of Gynecology and Obstetrics [FIGO]) and with predominantly high-grade neoplasms. They were managed by surgical exploration, tumor debulking where possible, and postoperative chemotherapy. A comparison with a contemporaneous series of 139 patients with primary epithelial ovarian carcinoma matched for stage and grade of disease and managed similarly showed no difference in actuarial survival. The median survival times were 11.3 months for patients with extraovarian serous papillary carcinomas and 13.5 months for patients with equivalent primary ovarian neoplasms. The features of the disease and the treatment regimens used are discussed.

Changing character of cervical cancer in young women.

To examine the hypothesis that the pattern of cervical cancer is changing data on women presenting with the disease over 34 years were studied retrospectively. During 1953-86, 2628 women with cervical cancer were referred to a large tertiary referral hospital in Sydney; 418 were aged 35 or less. During the period of review the proportion of young women with the disease increased from under 9% in the 1950s and 1960s to about 25% in the 1970s and 1980s; a similar but less pronounced trend was apparent for the whole of New South Wales in the 1970s and 1980s. The prevalence of less common morphological types of cervical cancer increased throughout the period, particularly in the young. Pelvic lymph node metastases were identified in younger patients with stage Ib and IIa tumours more commonly in the later years of the study, suggesting that the disease was becoming more severe. Overall rates of recurrence improved over time, but an apparent increase in early recurrences was observed in young patients with Ib and IIa tumours and without nodal disease. The results suggest that the clinical and pathological behaviour of cervical cancer changed over the period of review.

Ovarian carcinoma: abdominopelvic irradiation following reexploration.

Twenty patients with ovarian cancer, who following reexploration were left with residual disease nodules of less than 2 cm diameter, received abdominopelvic irradiation. Of these patients 18 had previous chemotherapy. Fifteen patients completed treatment, 13 of whom had prior chemotherapy. Six of the 18 patients with invasive tumors were alive and disease free 18-53 months postradiotherapy, while only 4 patients had died at the time of follow-up. No patient with residual nodules greater than 1 cm remained disease free. There was no difference in outcome between patients with microscopic or macroscopic less than 1 cm residuum. Complications were acceptable with 3/20 (15%) developing treatment-related intestinal obstruction.

Combination chemotherapy followed by surgery or radiotherapy in patients with locally advanced cervical cancer.

Forty-seven patients with locally advanced cervical cancer at high risk of relapse received three cycles of chemotherapy with PVB (cisplatin, vinblastine and bleomycin) before definitive local treatment with either radical surgery or radiotherapy. Thirty-one of the 47 patients (66%) responded to initial chemotherapy, and 11 of them have relapsed compared with 13 of the 16 non-responders. Median time to recurrence was 31 weeks for PVB non-responders but has not yet been reached for PVB responders. After a median follow-up of 128 weeks, 14 of the 31 responders (45%) are alive and disease free compared with 3 of the 16 non-responders (19%). There was a positive correlation between response to chemotherapy and subsequent response to radiotherapy. PVB was in general well tolerated although one death is probably attributable to chemotherapy. A randomized study comparing radiotherapy alone with initial PVB chemotherapy followed by radiotherapy is in progress.

Randomised comparison of procedures for obtaining informed consent in clinical trials of treatment for cancer.

Methods of obtaining informed consent have evolved differently in Western countries without substantive information on the impact of these different practices on the patients. A randomised study was performed to compare two commonly adopted methods of seeking consent to randomised treatment: an individual approach at the discretion of each doctor and a uniform policy of total disclosure of all relevant information. The impact of both consent procedures on the patient's understanding and anxiety levels and on the doctor-patient relationship was assessed by means of a questionnaire given soon after the consent interview. Fifty seven patients were assigned at random to two groups: to 29 patients an individual approach to seeking consent was adopted and to 28 patients all relevant information was given. Seven patients refused consent to randomised treatment, with slightly more refusals by patients in the total disclosure group (5 v 2, p = 0.25). The main effects of total disclosure of all information compared with an individual approach to seeking consent were: a better understanding of treatment and side effects and of research aspects of the treatments; less willingness to agree to randomised treatment; and increased anxiety. No significant differences were found in patients' perceptions of the doctor-patient relationship. A repeat questionnaire given three to four weeks later no longer showed significant differences between the two groups.

Combined cyclophosphamide, adriamycin and cis-platinum in advanced ovarian cancer resistant to chlorambucil and cis-platinum.

Seventeen patients with advanced ovarian adenocarcinoma recurring or progressing after prior treatment with chlorambucil and cis-platinum were treated with cyclophosphamide, adriamycin, and cis-platinum (CAP) every 3 weeks. In seven patients there was objective tumor response (41%) with a median response duration of 7.6 months and a survival advantage over nonresponders. Patients whose tumors had previously responded to chlorambucil or cis-platinum were less likely to respond to CAP than those who had not responded. Myelosuppression was the main toxicity, febrile neutropenia occurring after 8% of treatments.

Multifocal tumorigenesis in the upper female genital tract--implications for staging and management.

A review of 128 cases of "primary" ovarian müllerian carcinoma treated at the King George V Memorial Hospital was undertaken to determine the relative frequency with which such tumors were associated with evidence of multifocal primary neoplasia. Of the 128 cases studied, 115 were invasive carcinomas and 13 were noninvasive or borderline ovarian tumors ("tumors of low malignant potential"). Eight of 10 borderline serous ovarian tumors (80%) and 37 of 75 invasive serous carcinomas (49%) exhibited evidence of independent primary neoplasia at more than one anatomical site in the biopsy material available for review. Many of these cases represented bilateral primary ovarian tumors, but autochthonous extraovarian neoplasia was also commonly encountered. A single borderline endometrioid ovarian tumor and six of 15 endometrioid carcinomas (40%) were associated with biopsy-proven multifocal primary tumorigenesis. These were predominantly neoplasms in one or both ovaries plus adenocarcinoma in the uterine corpus. Other histological types of malignant common epithelial tumors of the ovaries did not demonstrate any such tendency, highlighting major differences in pathogenesis between members of this loosely associated group of ovarian cancers. Our study suggests that gynecological endometrioid and serous malignancies are commonly multifocal and we feel this has significant implications for the way these neoplasms are staged and therefore treated.

The integration of chemotherapy into the management of locally advanced cervical cancer: a pilot study.

Chemotherapy has been traditionally reserved as a last-time treatment for cervical cancer patients and in this setting long-term remissions are unusual. Platinum-based combination chemotherapy has been associated with high tumor response rates in patients with advanced and metastatic cervical tumors and past experience encouraged evaluation of chemotherapy as a first-line treatment in patients with locally advanced tumors where there is a high likelihood of relapse with local treatment. Thirty patients were treated initially with three courses of cis-platinum, vinblastine, and bleomycin with an overall response rate of 67%, and then had either radiotherapy or surgical resection. The initial results have been encouraging and the integration of chemotherapy into the management of locally advanced cervical cancer warrants further investigation.

Bowel complications in the management of ovarian cancer.

In a consecutive series of 163 patients referred with malignant ovarian tumours there were 24 (14.7%) who developed major bowel complications; 21 patients were operated upon for bowel obstruction and had a mean survival time of 8.1 months; 8 of the 24 patients are alive with cancer and 4 are alive without evidence of residual tumour. It is concluded that laparotomy is indicated when bowel complications occur in patients with ovarian carcinoma.