Is Transanal Local Excision Oncologically Safe After Chemoradiotherapy? A Multicenter Phase II Study in ycT0-1 Rectal Cancer.

PURPOSE: To evaluate the feasibility of local excision (LE) as an organ-preserving approach in patients with locally advanced rectal cancer showing a good response to neoadjuvant chemoradiotherapy (CRT). MATERIALS AND METHODS: This prospective, multicenter, single-arm phase II study enrolled patients with cT2-3N0-2M0 rectal adenocarcinoma downstaged to ycT0-1N0M0 after CRT. All patients underwent full-thickness LE. Patients with ypT0-1 were observed without completion total mesorectal excision (TME), whereas completion TME was recommended for those with ypT2-3 or positive margins. The primary endpoint was 3-year disease-free survival (DFS), with noninferiority defined as the lower bound of the one-sided 90% confidence interval (CI) exceeding 77.5%. The full analysis set (FAS) included all patients who underwent LE. RESULTS: Eighty patients were included [median follow-up, 74.2 months (Q1-Q3, 63.4-94.2)]. Pathology showed ypT0-1 in 62.5% and ypT2-3 in 37.5%. The 3-year DFS was 84.8% (lower 90% CI, 78.8%) in the FAS and 86.3% (lower 90% CI, 79.3%) in the per-protocol population. In the FAS, 5-year overall survival was 94.7%, and cumulative incidences of local recurrence (LR) and distant metastasis (DM) were 5.0%, and 8.9%, respectively. In subgroup analysis, 5-year DFS was 83.2% for ypT0-1, 88.9% for ypT2-3 with completion TME, and 75.3% for ypT2-3 without completion TME. The 30-day postoperative complications after transanal LE after CRT were 21.3%, and ≥ Clavien-Dindo grade 3 was 3.8%. CONCLUSION: LE met the prespecified non-inferiority criterion for 3-year DFS with excellent local control in patients with ycT0-1 after neoadjuvant CRT. Transanal LE can be considered as an alternative organ-preserving strategy in selected patients with major response after CRT with acceptable postoperative complications, provided that appropriate surveillance is ensured.