Survival impact and prognostic factors of secondary cytoreduction in platinum-sensitive recurrent ovarian cancer: a systematic review and trial-level meta-analysis
Secondary cytoreductive surgery is considered for selected patients with recurrent ovarian cancer. Although evidence supports its impact on progression-free survival, its effect on overall survival remains controversial. This study aims to identify patient sub-groups that benefit most from secondary cytoreductive surgery. A systematic review and trial-level meta-analysis of randomized controlled trials published through March 2025 was conducted. The primary end points were pooled hazard ratio (HR) for overall survival and progression-free survival comparing secondary cytoreductive surgery plus chemotherapy versus chemotherapy alone. Sub-group analyses were performed based on histology, platinum-free interval, number of recurrent lesions, individualized model or Arbeitsgemeinschaft Gynäkologische Onkologie score, and residual disease status. Three randomized controlled trials involving 1249 patients were included in this meta-analysis. Patients with favorable validated selection scores (positive Arbeitsgemeinschaft Gynäkologische Onkologie or individualized model ≤4.7) showed significantly improved overall survival (HR 0.79, 95% confidence interval [CI] 0.66 to 0.96). Complete resection was associated with significantly better overall survival (HR 0.53, 95% CI 0.43 to 0.64) and progression-free survival (HR 0.51, 95% CI 0.42 to 0.61) than patients who had residual disease. A progression-free survival benefit was also observed in the non-high-grade serous histology (HR 0.52, 95% CI 0.38 to 0.72). In patients with a platinum-free interval of 6 to 12 months (SOC-1, 6-16 months), there was a significant trend toward improved overall survival (HR 0.70, 95% CI 0.55 to 0.91). Secondary cytoreductive surgery significantly improves progression-free survival and provides an overall survival benefit in carefully selected patients, particularly, those with a high likelihood of complete resection, favorable surgical selection scores, and a shorter platinum-free interval (<16 months). These findings highlight the critical role of patient selection and surgical completeness in optimizing outcomes for recurrent ovarian cancer.