There is evidence that the survival of women with advanced ovarian cancer is improved when the surgeon is specifically trained to perform cytoreductive surgery and when there is centralization of care (168–171). Whenever feasible, patients with advanced ovarian malignancy should be referred to a subspecialty unit for primary surgery, and every effort should be made to attain as complete a cytoreduction as possible.
Stage I Epithelial Ovarian Cancer Early Stage, Low Risk
Guthrie et al. studied the outcome of 656 patients with early-stage epithelial ovarian cancer (140). Patients who had stage IA, grade 1 cancer and did not receive radiation or chemotherapy did not die of their disease; indicating that adjuvant therapy is unnecessary. The GOG carried out a prospective, randomized trial of observation versus melphalan for patients with stage IA and IB, grades 1 and 2 disease (114). Five-year survival for each group was 94% and 96%, respectively, confirming that adjuvant treatment did not improve survival. Therefore, no adjuvant chemotherapy is recommended for these patients.
Early Stage, High Risk
In patients whose disease is high risk (e.g., more poorly differentiated or in whom there are malignant cells either in ascites ﬂuid or in peritoneal washings), additional therapy is indicated. Most investigators recommend chemotherapy for these patients (172–185). Chemotherapy for patients with early-stage high-risk epithelial ovarian cancer can be either single agent or multiagent. Some researchers question the wisdom of overly aggressive chemotherapy in women with early-stage disease, suggesting that the evidence for a durable impact on survival is marginal (174,175,181). The risk of leukemia with alkylating agents and platinum make the administration of adjuvant therapy hazardous unless there is a significant benefit (186,187).
Because cisplatin, carboplatin, cyclophosphamide, and paclitaxel (Taxol) are active single agents against epithelial ovarian cancer, these drugs are administered in various combinations. There are some series in which cisplatin or cyclophosphamide (PC) or both have been used to treat patients with stage I disease (176–181). In a GOG trial of three cycles of cisplatin and cyclophosphamide versus intraperitoneal chromic phosphate (32P) in patients with stage IB and IC disease, the progression-free survival of women receiving the platinum-based chemotherapy was 31% higher than those receiving the radiocolloid (178). Similar results were reported by a multicenter trial performed in Italy by the Gruppo Italiano Collaborativo Oncologica Ginecologica (GICOG) for progression-free survival, although there was no overall survival advantage (179).
Two large parallel randomized phase III clinical trials were conducted on women with early-stage disease: the International Collaborative Ovarian Neoplasm Trial 1 (ICON1) and the Adjuvant Chemotherapy Trial in Ovarian Neoplasia (ACTION) (188,189).
In the ICON1 trial, 477 patients from 84 centers in Europe were entered. Patients of all stages were eligible for the trial if, in the opinion of the investigator, it was unclear whether adjuvant therapy would be of benefit. Most patients were considered to have stage I and IIA disease, but optimal surgical staging was not required, and it is likely that a significant number of these women had stage III disease. Adjuvant platinum-based chemotherapy was given to 241 patients, and no adjuvant chemotherapy was given to 236 patients. The 5-year survival was 73% in the group who received adjuvant chemotherapy compared with 62% in the control group (hazard ratio [HR] = 0.65, p = 0.01) (189).