Optimal number of neoadjuvant chemotherapy cycles prior to interval debulking surgery in advanced epithelial ovarian cancer: a systematic review and meta-analysis of progression-free survival and overall survival

Abstract

Objective: Neoadjuvant chemotherapy (NACT) represents a treatment option in patients with advanced epithelial ovarian cancer (AEOC) who are not good candidates for primary debulking surgery. Usually, 3 cycles of chemotherapy before surgery have been considered the best option for patient survival, although quite often some patients receive more than 3 cycles. The aim of this systematic review and meta-analysis was to identify the optimal number of NACT cycles reporting better survival in AEOC patients.

Methods: PubMed, Cochrane Library, and Scopus were searched for original articles that analyzed the relationship between the number of chemotherapy cycles and clinical outcomes in AEOC patients before interval debulking surgery (IDS). The main outcomes were progression-free survival (PFS) and overall survival (OS).

Results: A total of 22 studies comprising 7,005 patients diagnosed with AEOC were included in our analysis. In terms of survival, the reviewed studies dividing the patients in ≤3 NACT cycles vs. >3, showed a trend for a decrease in PFS and a significant reduction in OS with an increasing number of cycles, while a difference in both PFS and OS was revealed if early IDS included patients with 4 NACT cycles. These results should be interpreted with caution due to the complex characteristics of AEOC patients.

Conclusion: In conclusion, our review and meta-analysis revealed that there is not enough evidence to determine the optimal number of NACT treatments before surgery. Further research in the form of well-designed randomized controlled trials is necessary to address this issue.

Trial registration: PROSPERO Identifier: CRD42022334959.

Keywords: Cytoreductive Surgery; Neoadjuvant Chemotherapy; Ovarian Cancer; Prognosis; Survival.

Fig. 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart showing the selection of studies for the systematic review and meta-analysis and the stepwise exclusion.

AEOC, advanced epithelial ovarian cancer; IDS, interval debulking surgery; IP, intraperitoneal; NACT, neoadjuvant chemotherapy; OS, overall survival; PFS, progression-free survival.

Fig. 2. The forest plot for PFS (A) and OS (B) in studies with a NACT threshold of 3 shows a trend towards a poorer prognosis for patients undergoing delayed IDS, but this did not reach statistical significance. HRs are for NACT ≥4/NACT ≤3 and 95% CI.

CI, confidence interval; HR, hazard ratio IDS, interval debulking surgery; NACT, neoadjuvant chemotherapy; OS, overall survival; PFS, progression-free survival; SE, standard error.

Fig. 3. Forest plot for PFS (A) and OS (B) of studies with a NACT threshold set at 4 shows a significant decline in PFS for patients who underwent delayed IDS. However, only a tendency towards a worse OS was noted. HRs are for NACT ≥5/NACT ≤4 and 95% CI.

CI, confidence interval; HR, hazard ratio IDS, interval debulking surgery; NACT, neoadjuvant chemotherapy; OS, overall survival; PFS, progression-free survival; SE, standard error.