Doublet long-course TNT (capecitabine/oxaliplatin) improves DFS and pCR vs standard nCRT in high-risk LARC

Doublet-LC TNT integrates long-course radiotherapy (LCRT) with uninterrupted doublet chemotherapy (capecitabine + oxaliplatin; induction → concurrent → consolidation) before surgery, versus conventional neoadjuvant chemoradiotherapy (capecitabine + LCRT) followed by surgery and adjuvant chemo in a multicenter Phase III trial (TNTCRT; NCT03177382) in stage II/III high-risk locally advanced rectal cancer (n=458). At median 51 months’ follow-up, 3-year DFS was 74.8% vs 66.0% (HR 0.674; p=0.016) and 3-year metastasis-free survival was 77.7% vs 67.6% (HR 0.655), with pCR 26.37% vs 9.80% (p<0.001) and similarly low locoregional failure (~6% both arms); for context, modern TNT benchmarks like RAPIDO improved disease-related treatment failure at 3 years (23.7% vs 30.4%) with pCR ~28% (vs ~14%) but raised concerns about higher locoregional recurrence on longer follow-up, while PRODIGE 23 also improved DFS/MFS vs standard sequencing. Grade ≥3 neoadjuvant AEs were higher with doublet-LC TNT (27.59% vs 8.56%), but grade ≥3 toxicity across the full course (28.02% vs 24.32%) and major postoperative complications (3.98% vs 2.94%) were comparable.