SCRT (5×5Gy) + CAPOX Total Neoadjuvant Therapy Improves 5-Year OS vs Long-Course Capecitabine-CRT in LARC (STELLAR)

Short-course radiotherapy (SCRT; 5Gy×5) followed by consolidation chemotherapy (CAPOX) as total neoadjuvant therapy (TNT) was compared with standard long-course chemoradiotherapy (LCRT ~50Gy with concurrent capecitabine) in the Phase 3 STELLAR trial in distal/middle-third locally advanced rectal cancer (n=591; TNT n=302, CRT n=297; NCT02533271). At median follow-up 68.7 months, 5-year DFS was 62.0% with TNT vs 58.7% with CRT (HR 0.849, 95% CI 0.662–1.089), while 5-year OS favored TNT (78.1% vs 69.7%; HR 0.739, 95% CI 0.550–0.993)—an absolute +8.4% OS gain over the long-course CRT benchmark that has historically delivered ~70% 5-year OS in stage II–III populations treated with perioperative fluoropyrimidine-based chemoradiation. Distant metastasis and locoregional recurrence rates were similar, but in ESMO-defined high-risk patients TNT improved OS (HR 0.663) with a borderline DFS trend (HR 0.765), and among patients who recurred, TNT was associated with better postrecurrence PFS (HR 0.691) and postrecurrence survival (HR 0.698); earlier STELLAR reporting suggested higher grade ≥3 toxicity with the SCRT-TNT strategy vs CRT (26.5% vs 12.6%), so tolerability remains a key tradeoff.