Improved overall survival with combined chemotherapy and radiation in stage I uterine carcinosarcoma: A National Cancer Database study

Andrew Polio; Michael Goodheart; Jesus Gonzalez-Bosquet; Vincent Wagner

doi:10.1016/j.ygyno.2025.04.098

Objectives Uterine carcinosarcoma is a rare and aggressive cancer comprising less than 5 % of all uterine malignancies. Most patients will still present with early-stage disease. Unfortunately, there are higher rates of recurrence and worse survival than other histologies. This suggests the need for improved treatment strategies. Given the rarity of the disease, prospective, randomized data is lacking and treatment is informed largely by small retrospective studies. This study aimed to provide greater insight into appropriate adjuvant therapies in patients with uterine-confined carcinosarcoma. Methods Data from the National Cancer Database (NCDB) were analyzed for stage I uterine carcinosarcoma patients receiving no treatment (No Tx), chemotherapy alone (CT), radiation alone (RT) or combined chemotherapy and radiation (RT + CT). Kaplan-Meier survival analysis and Cox proportional hazards modeling, adjusted for confounding variables, were used to evaluate overall survival (OS). Results Among all stage I patients (n = 8394), the RT + CT group demonstrated a statistically significant improvement in OS compared to all other treatment groups. The 5-year OS rates were 69.9 % for RT + CT, 59.7 % for CT, 54.8 % for RT and 51.1 % for No Tx. The adjusted hazard ratio (HR) for RT + CT versus CT alone was 0.57 (95 % CI 0.52–0.63, P < 0.0001), indicating a 43 % reduction in mortality risk with the addition of radiation to chemotherapy, highlighting the superior benefit of multimodal adjuvant treatment. The multivariable Cox model identified several covariates significantly impacting OS, including advanced age (HR 1.04 per year increase, P < 0.0001), comorbid conditions (HR 1.47 for comorbidity score of 3, P < 0.0001), stage IB (vs IA) (HR 1.27, P < 0.0001) and presence of lymphovascular invasion (LVI) (HR 1.21, P = 0.0021). Race also influenced OS, with Black patients having a higher mortality risk (HR 1.24, P < 0.0001). The benefit of RT + CT remained significantly associated with improved OS after controlling for covariates (HR 0.691, 95 % CI 0.628–0.761). Subgroup analysis revealed the survival benefit of RT + CT persisted in both stage IA and IB patients. In stage IA, the 5-year OS for RT + CT was 76.1 % versus 66.9 % for CT alone. For stage IB, the 5-year OS was 66.1 % for RT + CT versus 54.0 % for CT alone. Within the RT + CT group, patients receiving vaginal brachytherapy (VB) showed greater survival benefit compared to those receiving external beam radiation therapy (EBRT). The adjusted HR for VB versus EBRT was 0.76 (95 % CI 0.66–0.88, P < 0.001). Conclusions Combined chemotherapy and radiation therapy significantly improved overall survival in patients with stage I uterine carcinosarcoma with consistent benefits in both stage IA and IB subgroups. This benefit persists after adjusting for key covariates, emphasizing its independent impact. Vaginal brachytherapy was associated with the greatest survival advantage among radiation modalities. These findings support incorporating combined modality treatment in managing early-stage uterine carcinosarcoma.

Improved overall survival with combined chemotherapy and radiation in stage I uterine carcinosarcoma: A National Cancer Database study

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