Background: Rectal squamous cell carcinoma (RSCC) is an extremely rare malignancy, whereas Anal squamous cell carcinoma (ASCC), though still uncommon, occurs more frequently.Definitive chemoradiation (CRT) remains the standard treatment for both tumors across disease stages.While previous studies reported overall survival advantages for ASCC, they did not evaluate stage-specific survival after CRT or assess whether treatment response differs between RSCC and ASCC across early and advanced disease.This study addresses this gap by comparing stage-stratified survival outcomes following definitive CRT between RSCC and ASCC using a large populationbased dataset.Methods: 17 population-based registries within the SEER database were used.Patients diagnosed with RSCC or ASCC who received both chemotherapy and radiation were included.Cases were grouped as localized or distant using the SEER Combined Summary Stage (2004+).Survival analyses were performed using Kaplan-Meier curves and the log-rank test (SPSS v27).Results: A total of 8,995 ASCC and 1,019 RSCC cases were included.In localized disease, survival after definitive CRT was comparable between ASCC and RSCC, with nearly identical 5-year survival (69.7% vs 70.0%, respectively; p = 0.592).In distant disease, however, outcomes diverged markedly: patients with advanced ASCC had significantly better 5-year survival compared with RSCC (50.0%vs 39.9%, respectively; p < 0.001), suggesting better CRT responsiveness in late-stage ASCC despite similar treatment. Conclusions:Our findings show that RSCC and ASCC have comparable survival after definitive chemoradiation in localized disease; however, a clear survival gap emerges in distant-stage tumors, with advanced RSCC showing significantly poorer outcomes despite receiving the same therapy.This pattern suggests potential biological or treatment-response differences that may limit CRT effectiveness in advanced RSCC.These results highlight the need for further studies to understand the reasons behind this disparity and to guide the development of more tailored treatment strategies-particularly for late-stage RSCC, where current CRT approaches appear insufficient.
Antonova et al. (2026) studied this question.