The role of intervention debulking surgery in advanced epithelial ovarian cancer: an EORTC Gynecological Cancer Cooperative Group study

Abstract

Chemotherapy is only moderately effective against advanced epithelial ovarian cancer. Patients with large residual tumors after primary surgery seldom attain long-term survival with chemotherapy alone, whereas patients with an optimal primary cytoreduction have a median survival of about 5 years. It is not clear whether the survival benefit associated with optimal cytoreduction is related to the tumor reduction itself or simply to selection of good-prognosis patients. In this prospective, randomized study, the European Organization for Research and Treatment of Cancer/Gynecological Cancer Cooperative Group investigated the effect of intervention debulking surgery on progression-free and overall survival in patients with advanced epithelial ovarian cancer. Eligible patients had epithelial ovarian carcinoma, International Federation of Gynecology and Obstetrics stage IIB-IV disease, lesions >1 cm after primary surgery, a performance status ≤2, and were ≤75 years old. After three cycles of cyclophosphamide-cisplatin, patients with stable disease or a response to chemotherapy were randomly assigned to undergo debulking surgery or to undergo no surgery, followed by further cyclophosphamide-cisplatin therapy. The study end-points were progression-free survival and overall survival. Of the 278 patients evaluable for progression-free and overall survival, 140 underwent debulking surgery and 138 did not. All known prognostic factors were well balanced between the two groups. The median follow-up was 3.5 years (maximum, 5.7). At intervention debulking surgery, 65% of the patients had lesions measuring>1 cm. In 45% of these patients, the lesions were surgically reduced to<1 cm. Surgery was not associated with death or severe morbidity. Intraoperative complications were observed in 5% of patients, and mild postoperative complications were observed in 14%. Progression-free and overall survivals were both significantly longer for the patients assigned to intervention debulking surgery (P= 0.01). Median progression-free survival was 18 months for the surgery group and 13 months for the no-surgery group. At 2 years follow-up, 38% of surgery patients and 26% of those who did not have surgery were alive and free of disease progression. Median survivals were 26 months (surgery) and 20 months (no surgery), and the proportion of patients alive at 2 years was 56% and 46%, respectively. Debulking surgery was an independent prognostic factor in the multivariate analysis(P= 0.012). Overall, after adjustment for all prognostic factors, surgery reduced the risk of death by 33% (P= 0.008) and significantly lengthened both progression-free and overall survival.