Early-onset rectal cancer shows aggressive presentation without age-dependent survival effect

The global rise in early-onset colorectal cancer (EORC) contrasts with declining rates in older adults, suggesting emerging environmental and biological influences. Data from non-Western populations, particularly India, remain scarce despite a young demographic and distinct tumor biology.

A retrospective analysis was performed on all patients with rectal adenocarcinoma treated at a tertiary cancer center in India (2016-2018). Patients were categorized as early-onset (≤45 years) or later-onset (>45 years). Clinicopathological features, MRI-based high-risk factors, and survival outcomes were compared. Overall survival (OS) and disease-free survival (DFS) were analyzed using Kaplan-Meier and Cox regression methods.

Among 1352 patients, 652 (48.2%) were early-onset. Younger patients had significantly higher rates of low rectal tumors (56.9% vs. 33.0%), poorly differentiated adenocarcinoma (44.3% vs. 17.4%), signet ring histology (24.2% vs. 6.9%), and advanced T (34.7% vs. 16.1%) and N (53.8% vs. 30.1%) stages (all p < 0.001). MRI-defined high-risk features, including mesorectal fascia and lateral node involvement, were more frequent in EORC. The unadjusted 3-year OS was lower in EORC (70.0% vs. 79.2%, p < 0.001), but DFS was similar. After multivariable adjustment, age was not an independent predictor of OS (HR 0.87, 95% CI 0.68-1.13, p = 0.30) while stage and aggressive histologic features were significant predictors.

EORC in India demonstrates an aggressive phenotype with advanced locoregional disease and high signet ring prevalence, contributing to worse unadjusted outcomes. However, after accounting for tumor biology and stage, age alone does not independently influence survival.