Higher local recurrence as the distinct failure pattern in early-onset rectal cancer: a tailored MRI score to guide therapy.

The unique biology of early-onset locally advanced rectal cancer (EOLARC) may drive distinct failure patterns, challenging current age-agnostic management. This multicenter retrospective study aimed to define these patterns compared to late-onset disease (LOLARC) and develop a tailored magnetic resonance imaging (MRI)-based risk score. We analyzed 1289 patients undergoing neoadjuvant chemoradiotherapy and surgery. After propensity score matching, EOLARC patients exhibited higher local recurrence rates (4.9% vs. 1.7%; P = 0.03) despite similar pathological complete response (pCR) rates (25.5% vs. 21.2%; P = 0.22). The novel mrTML score (incorporating tumor deposits, mesorectal fascia, and lateral lymph nodes) effectively predicted local recurrence (adjusted hazard ratio for score 3 vs. 0, 33.99). Notably, high pre-treatment risk persisted even among patients achieving pCR (HR 12.02; P = 0.003), highlighting failure patterns uncaptured by pathological response. The mrTML score is a robust tool to identify patients at high risk for local recurrence, providing an evidence-based framework for risk-adapted therapy.