Abstract
Objective: Metastatic rectal and rectosigmoid cancers remain associated with poor prognosis despite advances in systemic therapy. Although outcomes in metastatic colorectal cancer have improved overall, population-level survival trends specific to rectal cancer and their evolution across calendar time remain incompletely characterized.
Material and Methods: This population-based retrospective cohort study used data from the surveillance, epidemiology, and end results program. Adults diagnosed with metastatic rectal or rectosigmoid adenocarcinoma between 2000 and 2022 were included and categorized into prespecified diagnosis eras (2000-2007, 2008-2017, and 2018-2022). Overall survival (OS) was estimated by the Kaplan-Meier method and evaluated with multivariable Cox proportional hazards models adjusted for demographic and treatment-related factors. Adjusted survival curves were generated using regression standardization, and restricted mean survival time (RMST) was calculated over 60 months. Effect modification by age was assessed using stratified analyses and testing for interaction; proportional hazards assumptions were formally evaluated.
Results: A total of 33,277 patients with metastatic rectal or rectosigmoid cancer were included in the study. Median OS for the overall cohort was 16.2 months. Survival improved among patients diagnosed during 2008-2017 compared with those diagnosed during 2000-2007, with higher observed and adjusted survival estimates and longer RMST. In contrast, no statistically significant improvement in OS was observed in the most recent era (2018-2022). Older age was independently associated with worse OS, whereas receipt of chemotherapy and surgery to the primary tumor were associated with improved OS. Age-by-era interaction analyses did not demonstrate significant effect modification.
Conclusion: In this large population-based analysis, OS among patients with metastatic rectal and rectosigmoid cancer improved during the mid-diagnosis era, but appeared to plateau in more recent years. These findings indicate that survival gains have not occurred uniformly over time and underscore the importance of interpreting population-level outcomes within specific calendar eras and disease subtypes.