The optimal sequencing of surgery and chemotherapy in advanced epithelial ovarian cancer remains debated. While primary debulking surgery (PDS) has been considered the standard approach, recent randomized trials have questioned its survival advantage over neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). The study aimed to systematically evaluate phase III randomized controlled trials comparing PDS and NACT.

Following PRISMA guidelines (PROSPERO ID 1169057), PubMed and Scopus were systematically searched in October 2025 for phase III randomized clinical trials evaluating cytoreductive strategies in ovarian carcinoma. Only full-text English studies reporting overall survival (OS) or disease-free survival (DFS) were included. Risk ratios (RR) with 95% confidence intervals (CI) were calculated.

Five phase III trials (EORTC 55971, CHORUS, JCOG0602, SCORPION, TRUST) comprising 2296 patients met the inclusion criteria. PDS (n = 1139) and NACT (n = 1157) showed comparable OS (RR 0.99, 95% CI 0.94–1.03, p = 0.55, I² = 0%) and DFS (PDS RR 0.98, 95% CI 0.95–1.02, p = 0.27, I² = 0%). Subgroup analyses confirmed the absence of significant differences for patients with CC0 (RR 0.96, 95% CI 0.87–1.05, p = 0.35, I² = 0%), FIGO stage III disease (RR 0.97, 95% CI 0.92–1.03, p = 0.34, I² = 0%), or age under 70 years (RR 1.03, 95% CI 0.97–1.09, p = 0.38, I² = 0%).

PDS and NACT provide no significant survival outcomes in advanced ovarian cancer. No clear survival benefit for PDS was observed. Refinement of patient selection, integration of predictive biomarkers, and re-evaluation of PDS in the context of HIPEC and Poly-ADP-Ribose Polymerase (PARP) inhibitor use are warranted to guide individualized treatment strategies.