Clinicopathological characteristics and stage-adjusted outcomes of sporadic pMMR/MSS early-onset colorectal cancer

BACKGROUND: The global incidence of early-onset colorectal cancer (EOCRC) is increasing. The prognostic impact of EOCRC remains controversial, as it is largely confounded by hereditary syndromes and mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) tumors. We aimed to evaluate the clinicopathological features and stage-adjusted outcomes of sporadic, proficient MMR/microsatellite stable (pMMR/MSS) EOCRC. METHODS: We retrospectively reviewed 1,600 consecutive patients who underwent primary tumor resection for Stage 0-IV CRC. After excluding patients with known hereditary cancer syndromes or inflammatory bowel disease (IBD)-related CRC, as well as those with dMMR/MSI-H tumors or unknown MMR/MSI status, 1,218 patients with sporadic pMMR/MSS CRC were analyzed. Patients were stratified into EOCRC (< 50 years, n = 86) and late-onset CRC (LOCRC, ≥ 50 years, n = 1,132) cohorts. Cancer-specific survival (CSS) and time to recurrence (TTR) were evaluated. RESULTS: Patients with EOCRC were more often diagnosed at an advanced stage than those with LOCRC (P < 0.001). Unadjusted CSS was worse in the EOCRC group (P = 0.042); however, multivariable analysis showed that EOCRC was not an independent predictor of worse CSS (adjusted hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.49-1.37, P = 0.512). Among 987 patients with curatively resected Stage I-III disease, the EOCRC group received significantly more intensive perioperative treatments (P < 0.001). Unadjusted TTR did not significantly differ between the age groups (P = 0.510), and multivariable analysis showed a non-significant tendency toward a lower recurrence risk in patients with EOCRC (adjusted HR 0.52, 95% CI 0.23-1.03, P = 0.084). CONCLUSIONS: After exclusion of hereditary syndromes, IBD-related CRC, and dMMR/MSI-H tumors, pMMR/MSS EOCRC more often presented with advanced disease, but its stage-adjusted cancer-specific survival and recurrence outcomes did not significantly differ from those of LOCRC.