Background
Phase III RCT (GRECCAR-6). 265 patients with mid and low rectal cancer (cT3-T4) receiving standard preoperative CRT (45 Gy + capecitabine). Randomized 1:1 to surgery at 7 weeks versus 11 weeks after completing CRT. Primary endpoint: operative complications. Evaluated whether a longer interval to surgery improves pCR.
Interventions and follow up
Arm A: CRT (45 Gy + capecitabine) → TME at 7 weeks post-CRT
Arm B: CRT (45 Gy + capecitabine) → TME at 11 weeks post-CRT
Primary endpoint: Operative and postoperative morbidity at 30 day
mFollow up: 30 days (primary); 1 year
Arm B: CRT (45 Gy + capecitabine) → TME at 11 weeks post-CRT
Primary endpoint: Operative and postoperative morbidity at 30 day
mFollow up: 30 days (primary); 1 year
Results
pCR: 17.4% (11 wk) vs 13.7% (7 wk), P=.48 — not significant
Good pathologic response (ypT0-T1N0): 28.4% vs 25.0%, P=.59
Morbidity at 30 days: 44.5% (11 wk) vs 32.3% (7 wk), P=.04 — higher with longer interval
Complete mesorectal excision quality: 78.7% vs 90.3%, P=.008 — worse with longer interval
Good pathologic response (ypT0-T1N0): 28.4% vs 25.0%, P=.59
Morbidity at 30 days: 44.5% (11 wk) vs 32.3% (7 wk), P=.04 — higher with longer interval
Complete mesorectal excision quality: 78.7% vs 90.3%, P=.008 — worse with longer interval
Adverse events
Main adverse events: More operative complications at 11 weeks (44.5% vs 32.3%). Mesorectal excision quality significantly worse with delayed surgery. Anastomotic leakage: 15.9% vs 10.7% (NS). No significant difference in sphincter preservation.
Conclusions
A longer interval (11 vs 7 weeks) after preoperative CRT did not improve pCR and was associated with significantly more operative morbidity and worse mesorectal excision quality. These results argue against routinely extending the CRT-to-surgery interval beyond 7 weeks, though longer intervals may still be appropriate in select patients considering watch-and-wait.
Key Limitations
Key Limitations: The trial was designed to detect improved pCR with longer interval but was negative. Primary endpoint was morbidity — which also favored shorter interval. The finding that surgical quality was worse at 11 weeks is unexpected and challenges the premise of longer waiting periods. Not designed for watch-and-wait strategies — patients underwent definitive surgery in both arms. The observation that longer interval paradoxically worsens surgical quality may relate to fibrosis or tissue planes becoming less distinct.
Clinical Context
GRECCAR-6 provides data against routinely extending the CRT-surgery interval beyond 7–8 weeks for the purpose of improving pCR or surgical outcomes. However, the watch-and-wait paradigm (Renehan, van der Valk IWWD) supports longer intervals of restaging (≥12 weeks) specifically to identify clinical complete responders who can be managed non-operatively.
References
References: Lefèvre JH et al, J Clin Oncol 2016 (GRECCAR-6)