COLORECTAL cancer patients with late-stage II disease had significantly poorer five-year overall and recurrence-free survival than those with early-stage III disease, according to an analysis of 1,933 patients.
The study evaluated patients with stage II or III colorectal adenocarcinoma treated at two quaternary referral centres between January 2010 and December 2023. Researchers assessed short-term and long-term outcomes using univariate and multivariate survival models, alongside propensity score matching.
Patients with stage IIIA disease, defined as early node-positive disease, received adjuvant chemotherapy more frequently than patients with stage IIB/C disease, defined as T4N0 disease, with the difference being statistically significant (p<0.001).
Five-year overall survival and recurrence-free survival were significantly worse among patients with stage IIB/C disease than among those with stage IIIA disease (p<0.001 for both).
The observed survival difference remained after adjustment through multivariate analysis and propensity score matching, which accounted for high-risk factors and adjuvant chemotherapy.
For overall survival, the weighted hazard ratio for stage IIB/C versus IIIA was 3.020 (95% CI: 2.060–4.427), while the corresponding hazard ratio for stage IIIB/C versus IIIA was 3.456 (95% CI: 1.824–6.549).
For relapse-free survival, weighted hazard ratios were 3.030 (95% CI: 2.078–4.419) for stage IIB/C versus IIIA and 3.623 (95% CI: 1.950–6.729) for stage IIIB/C versus IIIA.
The findings identified a survival paradox in which patients with late-stage II colorectal cancer had poorer outcomes than those with early-stage III disease. Importantly, this difference persisted despite accounting for high-risk characteristics and adjuvant chemotherapy.
The researchers suggested that the finding may warrant reassessment of the current staging approach in the next iteration of the AJCC criteria. The results also highlighted a potential need to investigate whether optimised adjuvant treatment strategies could improve outcomes for patients with stage IIB/C disease.
A prospective investigation was proposed to further evaluate these findings and determine whether treatment approaches for this group should be refined.
Reference
Surendran A et al. Propensity score matching reveals a survival paradox in prognostic outcomes for late-stage II and early-stage III colorectal cancer patients. Sci Rep. 2026;DOI:10.1038/s41598-026-63826-z
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