Cytoreductive surgery in advanced epithelial ovarian cancer: a real-world analysis guided by clinical variables, homologous recombination, and BRCA status
Guidelines endorse both interval and primary debulking cytoreductive surgeries in the treatment of epithelial ovarian cancer, emphasizing that the treatment strategy should be tailored to the patient's clinical condition and tumor burden. Despite these recommendations, experts have yet to agree on a definitive surgical approach. A retrospective longitudinal analysis of 929 women diagnosed with advanced-stage (International Federation of Gynecology and Obstetrics stage III-IV) epithelial ovarian cancer between January 2002 and January 2025 was conducted. The effects of interval debulking surgery versus primary debulking surgery on median overall survival and progression-free survival were evaluated. Additionally, we aimed to identify patients who may benefit from a particular surgical approach based on clinical variables, mutation in either of the BRCA1 or BRCA2 genes, and homologous recombination profile. A total of 929 patients were diagnosed with stage III to IV disease (87.2%) and underwent either primary debulking (n = 389, 41.9%) or interval debulking surgery following neoadjuvant chemotherapy (n = 540, 58.1%). Patients treated with primary debulking had a longer median overall survival than those treated with interval debulking surgery (68.40 months, 95% CI 62.92 to 76.45 vs 52.01 months, 95% CI 47.15 to 57.86, HR 1.2, p = .0004). However, when adjusted for age at diagnosis, stage, histology, BRCA status, and tumor resectability, multivariate analysis demonstrated no significant difference in survival between the two surgical groups (HR 1.15, 95% CI 0.96 to 1.39, p = .12). Younger women (<69 years), stage III, and BRCA-wild-type and/or homologous recombination proficient had longer survival with primary debulking than with interval debulking surgery (74.55 months, 95% CI 65.35 to 93.27 vs 55.98 months, 95% CI 48.10 to 64.79, HR 1.38, p = .03). Patients with a pathogenic BRCA variant or homologous recombination deficient profile had similar survival outcomes with either debulking approach, regardless of age and disease stage (p > .05). Propensity score analysis demonstrated comparable median overall survival with the two surgical timings (64.39 months, 95% CI 58.38 to 71.23 vs 57.69 months, 95% CI 50.66 to 64.79, HR 1.33, p = .27). Our findings support the use of neoadjuvant chemotherapy followed by interval debulking surgery without compromising survival outcomes, regardless of age and stage, particularly among harder-to-treat patients. We identified a specific subset of patients who may benefit from primary debulking surgery as the optimal intervention. These findings advocate for a personalized treatment approach and the potential for tailored surgical strategies guided by patient clinical variables, homologous recombination, and genetic factors.