Prolonging nCRT→TME interval to 12 weeks fails to boost pCR in stage II–III rectal cancer (RCT)

Long-course neoadjuvant chemoradiotherapy (50Gy with concurrent 5-fluorouracil) followed by total mesorectal excision (TME) was tested in an RCT of locally advanced rectal cancer (MRI-staged stage II–III adenocarcinoma ≤12cm from the anal verge), randomizing patients to surgery at ~8 vs ~12 weeks post-nCRT (n=124; 61 vs 63). Pathologic complete response (pCR; Dworak grade 4) was essentially identical (14.8% vs 14.5%; p=0.904), with no meaningful differences in ypT/ypN stage, circumferential resection margin positivity, or TME quality; 3-year OS (76.3% vs 80.0%; p=0.657) and DFS (62.9% vs 62.2%; p=0.838) were also similar—broadly in the range seen with conventional long-course CRT→TME where pCR is typically ~10–30% across series. Safety/surgical signals were directionally worse with delay, with higher anastomotic leak numerically at 12 weeks (15.9% vs 4.9%), while adjuvant chemotherapy use was higher in the 8-week arm (61.7% vs 39.7%; p=0.015), complicating clean DFS/OS interpretation (NCT03607370).