Abstract Background Colorectal mucinous adenocarcinoma (MAC) is challenging due to its unique pathophysiology and increasing incidence in younger populations. Treatment guidelines for early‐onset MAC remain unclear, with clinical decisions often based on extrapolated data from classical adenocarcinoma. We aimed to assess the association between the extent of surgical resection and systemic therapy in patients with early‐onset colonic MAC and survival. Methods Retrospective cohort analysis of patients aged 20–50 with stage II–III colonic MAC using the SEER database (2000–2020). We evaluated overall survival (OS) and cancer‐specific survival (CSS) based on surgical resection (segmental vs. extended) and systemic therapy, using Kaplan–Meier and Cox regression analyses. Results The cohort included 2553 patients (58.5% male; mean age 42.7 years). Segmental resection was performed in 27.6%. Extended resection was more commonly performed in right‐sided and stage III disease. Systemic therapy was administered to 62.1%, predominantly for stage III disease with unfavourable tumour features. Systemic therapy was associated with improved restricted mean 5‐year CSS (51.7 vs. 47.8 months, p = 0.041) and OS (51.1 vs. 45.9 months, p = 0.008) in stage III, but not stage II, disease. Extended resection was associated with a modest survival benefit for CSS (56.5 vs. 54.3 months, p = 0.027) and OS (56.0 vs. 53.3 months, p = 0.007) in stage II, but not stage III, disease. Conclusion Systemic therapy was associated with a significant survival benefit in patients with stage III early‐onset MAC, supporting its role as a cornerstone of treatment despite the histology's presumed chemoresistance.
Perrone et al. (2026) studied this question.