Neoadjuvant chemotherapy followed by interval debulking was not inferior to the standard therapy of primary surgery followed by chemotherapy.
Standard therapy for advanced ovarian cancer consists of primary debulking surgery followed by chemotherapy. But some patients present with clinical features (e.g., extensive comorbid conditions, poor performance status, radiologically determined unresectable disease) that can preclude surgical intervention. Neoadjuvant therapy before cytoreductive surgery has been studied; however, a meta-analysis involving 835 patients showed that neoadjuvant chemotherapy was associated with worse prognosis (Gynecol Oncol 2006; 103:1070).
Now, investigators randomized 670 patients with stage IIIC or IV epithelial ovarian, fallopian, or peritoneal cancer to primary debulking surgery followed by platinum-based chemotherapy or to 3 cycles of platinum-based neoadjuvant therapy followed by interval debulking surgery and subsequent continuation of chemotherapy. The primary endpoint was overall survival (OS). The ultimate goal was complete resection of all macroscopic disease, whether performed as primary treatment or after neoadjuvant chemotherapy.
The largest residual tumor was 1 cm in 41.6% of patients after primary debulking and in 80.6% of patients after interval debulking. In an intent-to-treat analysis, median OS (29 months in the primary surgery group vs. 30 months in the neoadjuvant group) and median progression-free survival (12 months each) were similar in the two groups. The hazard ratio for death in the neoadjuvant group compared with the primary surgery group was 0.98 (P=0.01 for noninferiority). Post hoc analysis did not reveal any subgroup in which one treatment was superior to the other. In descending order, the strongest independent predictors of prolonged survival were absence of residual tumors after surgery (P<0.001), stage IIIC disease (P=0.001), small tumor size before randomization (P=0.001), endometrioid histology (P=0.005), and younger age (P=0.005). The authors concluded that neoadjuvant chemotherapy followed by interval debulking was not inferior to primary debulking surgery.
Comment: This study confirms the role of neoadjuvant chemotherapy followed by interval debulking for the management of patients with advanced ovarian cancer, particularly those whose condition at diagnosis limits surgical intervention. The issue is whether this approach should supersede primary surgery as a treatment option. Given the noted advantage of intraperitoneal chemotherapy in patients whose disease has been optimally debulked, the standard of care should remain primary surgical cytoreduction. Nonetheless, neoadjuvant therapy has other advantages; moreover, the approach is useful for assessing novel cytotoxic and biological therapeutics and might prove particularly beneficial in a selected cohort of patients.
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