Treatment Outcomes and Toxicity of Cisplatin-Etoposide-Based Regimens and Carboplatin-Paclitaxel as Adjuvant Chemotherapy for Ovarian Adult Granulosa Cell Tumors: A Multicenter Retrospective Cohort Study.

Background/Objectives: Adult granulosa cell tumors (AGCTs) of the ovary are rare sex cord-stromal malignancies characterized by an indolent clinical course and a persistent risk of late recurrence. Although adjuvant chemotherapy is considered for selected patients with higher-risk disease, the optimal platinum-based regimen remains uncertain because comparative evidence is limited. This study compared disease-free survival (DFS), treatment delivery, and toxicity between bleomycin-etoposide-cisplatin/etoposide-cisplatin (BEP/EP) and carboplatin-paclitaxel (CP) in the postoperative adjuvant setting. Methods: This retrospective, multicenter, nonrandomized comparative cohort study included 58 patients with AGCTs who underwent primary surgery and received adjuvant platinum-based chemotherapy at five tertiary oncology centers in Türkiye between 2010 and 2024. Patients received BEP/EP or CP according to institutional practice and physician discretion. The primary endpoint was disease-free survival (DFS), while secondary endpoints included treatment delivery and treatment-related toxicity. Results: A total of 58 patients were included, with 26 receiving BEP/EP and 32 receiving CP. Patients treated with CP were older, whereas fertility-sparing surgery was more common in the BEP/EP group. After a median follow-up of 75.5 months, 14 recurrences were observed; when deaths without prior recurrence were included according to the prespecified DFS definition, a total of 19 DFS events occurred. Median DFS was 77.2 months in the BEP/EP group and 126.2 months in the CP group. The estimated 5-year DFS rates were 75.5% and 83.5%, respectively, with no statistically significant difference between treatment groups (log-rank p = 0.296). In an exploratory multivariable Cox model restricted to age and treatment regimen, increasing age was associated with a higher risk of a DFS event (adjusted HR 1.046 per year, 95% CI 1.011-1.082; p = 0.010), whereas CP versus BEP/EP was not significantly associated with DFS (adjusted HR 0.426, 95% CI 0.167-1.083; p = 0.073). Treatment completion rates were numerically higher with CP (84.4% vs. 69.2%; p = 0.17). Peripheral neuropathy occurred more frequently with CP (p = 0.007), whereas nephrotoxicity occurred only in the BEP/EP group (p = 0.014). Pulmonary toxicity was observed only with bleomycin-containing treatment, and one patient developed secondary acute myeloid leukemia following BEP. Conclusions: No statistically significant difference in DFS was detected between BEP/EP and CP, while distinct toxicity patterns were observed. Given the retrospective design, limited sample size, and potential for treatment-selection bias and residual confounding, these findings should be considered exploratory and should not be interpreted as evidence of equivalent efficacy between the regimens.