The standard of care for patients with advanced ovarian cancer has been primary debulking surgery; ovarian carcinoma is often not diagnosed until it is at an advanced stage. Treatment involving neoadjuvant chemotherapy prior to interval debulking surgery has been investigated by several institutions, but prospective, randomized, controlled trials assessing the role of primary debulking surgery in the treatment of advanced ovarian cancer have not been conducted. However, such a study would provide needed clarification concerning these treatments, because a meta-analysis involving 835 patients indicated that neoadjuvant chemotherapy resulted in a worse outcome as compared to primary debulking surgery.
In the September 2, 2010 edition of the New England Journal of Medicine, Ignace Vergote et al., reported for the the EORTC Gynecological Cancer Group and the NCIC–Clinical Trials Group on a Gynecologic Cancer Intergroup study, the results of the EORTC 55971 trial demonstrating that neoadjuvant chemotherapy followed by interval debulking surgery is not inferior to primary debulking surgery followed by chemotherapy as a treatment option for patients with bulky stage IIIC or IV ovarian carcinoma. In this study 670 patients with biopsy-proven stage IIIC or IV invasive epithelial ovarian carcinoma, primary peritoneal carcinoma, or fallopian-tube carcinoma were randomly assigned to receive either primary debulking surgery followed by platinum-based chemotherapy or to receive neoadjuvant platinum-based chemotherapy followed by interval debulking surgery and then platinum-based chemotherapy. Comparing the group assigned to neoadjuvant chemotherapy followed by interval debulking to the group assigned to primary debulking surgery followed by chemotherapy, the hazard ratio for death (intention to treat analysis) was 0.98 (90% CI, 0.84 to 1.13; P = 0.01 for noninferiority), and the hazard ratio for progressive disease was 1.01 (90% CI, 0.89 to 1.15). Complete resection of all macroscopic tumors (at primary or interval surgery) was the strongest independent variable predicting overall survival. The authors note that whenever debulking surgery is performed, be it as the primary treatment or following neoadjuvant chemotherapy, complete resection of all macroscopic disease should be the objective. Interval debulking was associated with a lower postoperative mortality, shorter operation time, less grade 3 hemorrhage, venous complications and infections.
Vergote concludes “This study is the first randomized study on surgery in the primary treatment of advanced ovarian cancer. The study shows neoadjuvant chemotherapy followed by interval debulking results in the same survival but fewer complications than primary debulking surgery. Surgical consultation and careful analysis of important predictive factors of debulking surgery resulting in no residual macroscopic tumor, such as co-morbidities, age, disease burden, location of metastatic sites, performance status, and stage, should be taken into account when deciding whether a patient is a candidate for primary debulking surgery with an acceptable morbidity. In addition to computerized axial tomography and/or positron emission tomography, laparoscopy might provide additional information on the disease burden.
EORTC, Medical Science Writer
 Bristow RE, Chi DS. Platinum-based neoadjuvant chemotherapy and interval surgical cytoreduction for advanced ovarian cancer: a meta-analysis. Gynecol Oncol 103:1070-6, 2006.  Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, Verheijen RHM, van der Burg MEL, Lacave AJ, Panici PB, Kenter GC, Casado A, Mendiola C, Coens C, Verleye L, Stuart GCE, Pecorelli S, and Reed NS, for the Gynecologic Cancer Intergroup study of the European Organization for Research and Treatment of Cancer–Gynaecological Cancer Group and the NCIC–Clinical Trials Group. Treatment Options in Stage IIIc or IV Ovarian Cancer: Neoadjuvant Chemotherapy or Primary Surgery in Stage IIIC or IV Ovarian Cancer. N Engl J Med 363(10):943-953, 2010.