Ten-Year Outcomes in Colorectal Cancer—Competing Risks and Patient Vulnerability: A Prospective Multicenter Observational Study

Background: As survival after colorectal cancer (CRC) has improved, an increasing proportion of patients live beyond five years, making long-term outcomes increasingly relevant. In addition to cancer-related mortality, survivors remain at risk of death from other causes influenced by clinical and psychosocial vulnerabilities. Methods: We conducted a 10-year prospective cohort study including 838 patients with stage I-IV CRC treated in public hospitals in the Basque Country (Spain). Patients were recruited between November 2010 and December 2012 and followed for up to 10 years after surgery. Clinical, sociodemographic, lifestyle, and patient-reported outcomes were collected. Competing risk regression models (Fine-Gray) were used to estimate sub-distribution hazard ratios (sHRs) for CRC-specific and non-CRC mortality, stratified by tumor site and sex. Results: After 10 years, 40% of patients had died, with 66% of deaths attributable to CRC and 34% to other causes. CRC-specific mortality was mainly driven by tumor-related factors, including advanced stage (stage IV: sHR 7.18, p < 0.001) and residual disease after surgery (R1/R2: sHR 2.68; p < 0.001), with larger effect sizes observed in rectal cancer. In contrast, non-CRC mortality was associated with patient vulnerability, including age ≥75 years (sHR 3.57, p < 0.001), absence of adjuvant chemotherapy (sHR 5.59, p < 0.001), anemia, alcohol consumption, and poor functional status. Patients with rectal cancer and women reported poorer baseline quality of life. Sex-stratified analyses suggested differential patterns of vulnerability, with psychosocial and quality-of-life-related factors appearing more relevant in women, whereas lifestyle and clinical factors appeared more prominent in men. Conclusions: Long-term mortality in CRC reflects the interplay between tumor-related factors and patient vulnerability. Competing risk models allow a more accurate characterization of cause-specific outcomes and may help identify high-risk subgroups for tailored follow-up and management strategies.