Use and Effectiveness of Neoadjuvant Chemotherapy for Treatment of Ovarian Cancer

Abstract

Purpose In 2010, a randomized clinical trial demonstrated noninferior survival for patients with advanced ovarian cancer who were treated with neoadjuvant chemotherapy (NACT) compared with primary cytoreductive surgery (PCS). We examined the use and effectiveness of NACT in clinical practice. Patients and Methods A multi-institutional observational study of 1,538 women with stages IIIC to IV ovarian cancer who were treated at six National Cancer Institute-designated cancer centers. We examined NACT use in patients who were diagnosed between 2003 and 2012 (N = 1,538) and compared overall survival (OS), morbidity, and postoperative residual disease in a propensity-score matched sample of patients (N = 594). Results NACT use increased from 16% during 2003 to 2010 to 34% during 2011 to 2012 in stage IIIC disease ( Ptrend < .001), and from 41% to 62% in stage IV disease ( Ptrend < .001). Adoption of NACT varied by institution, from 8% to 30% for stage IIIC disease (P < .001) and from 27% to 61% ( P = .007) for stage IV disease during this time period. In the matched sample, NACT was associated with shorter OS in stage IIIC disease (median OS: 33 v 43 months; hazard ratio [HR], 1.40; 95% CI, 1.11 to 1.77) compared with PCS, but not stage IV disease (median OS: 31 v 36 months; HR, 1.16; 95% CI, 0.89 to 1.52). Patients with stages IIIC and IV disease who received NACT were less likely to have ≥ 1 cm postoperative residual disease, an intensive care unit admission, or a rehospitalization (all P ≤ .04) compared with those who received PCS treatment. However, among women with stage IIIC disease who achieved microscopic or ≤ 1 cm postoperative residual disease, NACT was associated with decreased OS (HR, 1.49; 95% CI, 1.01 to 2.18; P = .04). Conclusion Use of NACT increased significantly between 2003 and 2012. In this observational study, PCS was associated with increased survival in stage IIIC, but not stage IV disease. Future studies should prospectively consider the efficacy of NACT by extent of residual disease in unselected patients.

Conflict of interest statement

Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

Figures

Fig 1.

(A) Stage IIIC disease. (B) Stage IV disease. Use of neoadjuvant chemotherapy (NACT) increased significantly over time (Ptrend < .001 for both groups). Intraperitoneal and intravenous (IP/IV) chemotherapy is shown for comparison. Three patients with stage IIIC disease and one with stage IV who were diagnosed in 2003 are included in the estimate for 2004. Twenty-three patients with stage IIIC disease and seven with stage IV who were diagnosed in 2012 are included in the estimate for 2011. PCS, primary cytoreductive surgery.

Fig 2.

Kaplan-Meier survival plots within propensity-score matched samples, separately by treatment with neoadjuvant chemotherapy (NACT) versus primary cytoreductive surgery (PCS). (A) Stage IIIC disease. (B) Stage IV disease. (C) Stage IIIC disease, ≤ 1 cm or optimal. (D) Stage IIIC disease, R0 resection. Panels C and D are limited to matched pairs who received interval cytoreductive surgery (NACT-ICS) versus PCS.

Fig A1.

Study cohort. IP/IV, intraperitoneal and intravenous; NACT, neoadjuvant chemotherapy; NCCN, National Comprehensive Cancer Network; PCS, primary cytoreductive surgery.

Fig A2.

Sensitivity analysis including patients who received intraperitoneal and intravenous chemotherapy: Kaplan-Meier survival plots within propensity-score matched samples. (A) Stage IIIC disease. (B) Stage IV disease. NACT, neoadjuvant chemotherapy; PCS, primary cytoreductive surgery.