From chemotherapy to checkpoints: Survival trends in rectal adenocarcinoma.

Abstract

e15594 Background: Colorectal cancer is the fourth most common malignancy worldwide and the second leading cause of cancer-related mortality in the United States. Adenocarcinoma accounts for approximately 90% of cases, with nearly one-third arising in the rectum. Management of rectal adenocarcinoma has evolved over the past two decades with advances in multimodality therapy and the introduction of immunotherapy. Pembrolizumab was approved in 2017 for select molecular subtypes of colorectal cancer. Our aim was to evaluate overall survival differences before (2005–2016) and after (2017–2022) 2017 and to assess associated sociodemographic and clinical factors. Methods: We conducted a retrospective cohort study using the SEER Plus database (December 2025 release) and identified patients diagnosed with rectal adenocarcinoma between 2005 and 2022 using ICD-O-3 code 8140/3 and site code C20.9. We stratified patients into pre-2017 and post-2017 cohorts, extracting 55,833 and 40,572 cases, respectively. We then used multivariable Cox proportional hazards regression models to assess associations between overall survival and age, sex, race, stage, median household income, and treatment modalities (surgery, chemotherapy, radiotherapy). Statistical analyses were performed using GraphPad Prism version 10.6.1, with p values < 0.05 considered statistically significant. Results: Each 1-year increase in age was associated with a 3.6% higher risk of death pre-2017 and a 3.4% higher risk post-2017 (p < 0.0001). Female sex was associated with an 11% lower risk of death pre-2017 and a 13% lower risk post-2017 compared to males (p < 0.0001). Distant stage was associated with a 3.5-fold higher risk of death in both eras (p < 0.0001). Higher income ( > 100K) was associated with a 14% lower risk pre-2017 and 16% lower risk post-2017 compared to income < 100K (p < 0.0001). Radiotherapy was associated with a 7% lower risk pre-2017 and 14% lower risk post-2017 versus no radiotherapy (p < 0.0001). Chemotherapy was associated with a 30% lower risk pre-2017 and 50% lower risk post-2017 versus no chemotherapy (p < 0.0001). Surgery was associated with a 60% lower risk pre-2017 and 74% lower risk post-2017 versus no surgery (p < 0.0001). Conclusions: Overall survival for rectal adenocarcinoma improved modestly in the post-2017 era, with greater gains across sex, income, and treatment subgroups, while age and advanced stage remained dominant predictors. These improvements likely reflect advances in systemic therapy, local control, screening, and multidisciplinary care. Although the post-2017 period coincides with the adoption of pembrolizumab, we did not assess immunotherapy exposure directly, precluding attribution of benefit specifically to checkpoint inhibition. Further studies incorporating molecular and treatment-specific data are needed to define the impact of immunotherapy and address socioeconomic disparities in rectal cancer outcomes.