Therapeutic outcomes and prognostic determinants of neoadjuvant chemotherapy plus interval debulking surgery compared with primary debulking surgery in advanced-stage epithelial ovarian cancer

Objective To compare the therapeutic outcomes of neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) and primary debulking surgery (PDS) in patients with advanced epithelial ovarian cancer (AEOC) and to evaluate factors associated with prognosis. Methods This retrospective study included 97 patients with AEOC treated between April 2015 and July 2020. According to treatment strategy, 36 patients underwent PDS and 61 underwent NACT-IDS. Overall survival (OS), progression-free survival (PFS), and perioperative outcomes were compared between the two groups. Kaplan–Meier analysis and Cox proportional hazards regression were used to evaluate survival outcomes. Additional adjusted models were used to account for baseline imbalance. Because CA-125 normalization occurred after treatment initiation, it was defined as a serum CA-125 concentration of ≤35 U/mL and analyzed as a time-dependent covariate. Results Significant baseline differences were observed between the groups in age, BMI, baseline CA-125 level, and FIGO stage (all P<0.05). During a median follow-up of 43 months [95% CI (39.87, 50.32)], 53 of 97 patients (54.64%) died. Median OS was 41 months in the PDS group and 43 months in the NACT-IDS group, and median PFS was 20 months in both groups. No significant differences were found in unadjusted OS or PFS between the groups (OS: log-rank P = 0.484; PFS: log-rank P = 0.410). After adjustment for age, BMI, log-transformed baseline CA-125 level, and FIGO stage, treatment strategy was not associated with OS [adjusted HR = 0.88, 95% CI (0.49, 1.58), P = 0.667] or PFS [adjusted HR = 1.07, 95% CI (0.64, 1.79), P = 0.798]. Patients who achieved complete cytoreduction (R0) had longer median OS than those with incomplete cytoreduction (R1+R2) [43 vs. 38 months, P = 0.025] and longer median PFS [22 vs. 18 months, P = 0.040]. After adjustment, NACT-IDS remained associated with shorter operation time, lower intraoperative blood loss, earlier initiation of postoperative chemotherapy, and a lower likelihood of drainage-tube placement, whereas its association with postoperative complications was no longer statistically significant. Residual disease was associated with higher mortality [adjusted HR = 2.61, 95% CI 1.10–6.18, P = 0.029]. CA-125 normalization was associated with lower hazards of death [time-dependent adjusted HR = 0.59, 95% CI 0.35–0.99, P = 0.047] and progression or death [time-dependent adjusted HR = 0.63, 95% CI 0.42–0.95, P = 0.026]. Conclusion In this exploratory single-center retrospective non-randomized cohort, NACT-IDS was associated with shorter operation time, lower intraoperative blood loss, earlier initiation of postoperative chemotherapy, and less frequent drainage-tube placement than PDS, but not with a significantly lower adjusted postoperative complication rate or with OS or PFS. These findings should not be interpreted as evidence of equivalent survival efficacy or causal treatment benefit. Residual disease was associated with poorer survival, whereas documented CA-125 normalization showed a favorable time-dependent prognostic association.