Radiotherapy for female non-gynecologic pelvic and adjacent cancers and secondary uterine Cancers: a SEER analysis

Population-based evidence on the incidence and long-term risk of secondary uterine cancer after radiotherapy (RT) for non-gynecologic pelvic cancers remains limited. This study evaluated the incidence, temporal risk patterns, and survival outcomes of secondary uterine cancers after RT.

Female patients with rectal cancer (RC), bladder cancer (BC), or lower pelvic cancers (LPC) were identified from the Surveillance, Epidemiology, and End Results database. Competing-risk regression models were used to estimate hazard ratios for secondary uterine cancer. Hazard ratios (HR) and standardized incidence ratios (SIRs) quantified excess risk associated with RT. Dynamic HR analyses were conducted by latency, age, and calendar year. Overall survival (OS) was evaluated with Kaplan-Meier analysis with propensity score matching.

The 20-year cumulative incidence of secondary uterine cancer was significantly higher in the RT groups than in the non-RT groups for patients with RC (2.59% vs. 0.84%), BC (1.46% vs. 0.41%), and LPC (2.30% vs. 0.80%). In multivariable analyses, RT remained an independent risk factor for the RC group (HR = 2.17, 95% CI 1.49-3.15) and BC group (HR = 2.82, 95% CI 1.06-7.48). Adjusted HRs were 3.36 for RC, 4.02 for BC, and 2.84 for LPC, predominantly driven by uterine corpus cancer, with corresponding SIRs of 3.04, 3.19, and 2.69. Among patients who developed secondary uterine cancer, those with prior RT demonstrated poorer observed OS than those without prior RT.

Radiotherapy for female pelvic cancers was associated with an increased long-term risk of secondary uterine cancer regardless of irradiation direction, although the absolute excess risk was modest. These findings suggest that the uterus may be a susceptible organ during pelvic radiotherapy and support risk-adapted treatment planning and long-term surveillance.