Germline Mutations in Ovarian Carcinosarcoma: No Impact on Progression-Free Survival

A recent study evaluating the role of germline mutations in ovarian carcinosarcoma (OCS) found that these mutations do not significantly impact progression-free survival (PFS) or residual disease burden at surgery. Among patients who underwent germline testing, 21.0% had a detectable mutation, but their median PFS (14.0 months) was not significantly different from those without a germline mutation (15.6 months; hazard ratio [HR] = 0.70, P = .34). Given the rarity of OCS, larger studies are needed to further investigate the clinical implications of germline and somatic mutations in this population. 

OCS is a rare and aggressive biphasic tumor of the fallopian tube, ovary, and peritoneum, accounting for less than 5% of all ovarian carcinomas. Due to its rarity, optimal management strategies remain unclear, and patients with OCS are often excluded from clinical trials evaluating novel targeted therapies. Germline and somatic mutations have significantly influenced treatment paradigms in ovarian cancer, but their role in OCS remains largely unknown. This study aimed to determine the prevalence of germline and somatic mutations in patients with OCS and assess their impact on cancer-related outcomes. 

Researchers conducted a retrospective cohort study of patients diagnosed with OCS at Brigham and Women's Hospital between 2005 and 2023. OCS was confirmed through expert pathologic review, and patients without clinical or follow-up data were excluded. Statistical analyses, including chi-square testing and hazard ratios, were used to evaluate PFS and overall survival (OS) based on germline mutation status. 

A total of 112 patients were diagnosed with OCS during the study period, with most presenting with stage III disease (60.9%). Of the 62 patients (55.3%) who underwent germline testing, 13 (21.0%) had a positive germline mutation. Additionally, 43 patients (69.4%) had identifiable somatic mutations. Tumor characteristics showed that most cases were mismatch repair proficient, homologous recombination deficiency negative, and had low tumor mutation burden. There were no significant differences in initial treatment choice, extent of surgical excision, residual disease at surgery, or type and duration of chemotherapy between those with and without germline mutations. Maintenance therapy use was low in both groups, with 8.3% of mutation carriers receiving a PARP inhibitor compared to 6.3% of non-carriers. The median PFS for the entire cohort was 13.1 months, and the median OS was 37.4 months. 

“Germline mutations are found in approximately one-quarter of patients with OCS,” the authors concluded. “Germline mutation status does not appear to impact residual disease burden at the time of surgery or PFS, though we were limited by a small sample size.” 

Reference 
Abel MK. The impact of germline mutations in patients with ovarian carcinosarcoma. Paper presented at: Society of Gynecologic Oncology 2025 Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle, WA. Accessed March 11, 2025. https://www.sgo.org/events/annual-meeting/