Neoadjuvant S‐1 and oxaliplatin plus bevacizumab therapy for high‐risk locally advanced rectal cancer: A prospective multicenter phase II study

Aim We report the short/mid‐term results of surgery for high‐risk locally advanced rectal cancer (LARC) after neoadjuvant chemotherapy (NAC, four courses of S‐1 + oxaliplatin+ bevacizumab) without radiotherapy with the primary aim of ypT0‐2. Methods High‐risk LARC was defined as cT4b, mesorectal fascia (MRF) ≤1 mm (MRF+), or lateral lymph node metastasis (cLLN+) on high‐resolution MRI. The planned 32 cases from April 2018 to December 2021 were all included. Results There were 10 patients at cT4b (31.2%), 26 MRF+ (81.3%), and 22 cLLN+ (68.8%). Thirteen (40.6%) underwent NAC after a colostomy for stenosis. NAC was completed in 26 (81.2%) cases. Grade 3 or higher adverse events occurred in six (18.7%). One patient developed progressive disease (3.2%). Eleven were ycT0‐3MRF‐LLN‐ (34.3%). Curative‐intent surgery was performed on 31, with sphincter‐preserving surgery in 20, abdominoperineal resection in nine, total pelvic exenteration in two, and lateral lymph node dissection in 24. Two had R1/2 resection (6.4%). A Grade 3 or higher postoperative complication rate occurred in 3.2%. Pathological complete response and ypT0‐2 rates were 12.9% and 45.1%. Three‐year disease‐free survival rates (3yDFS) for ypT0‐2 and ypT ≥3 were 81.2%, 46.6% (p = 0.061), and 3‐year local recurrence rates (3yLR) were 0%, 48.8% (p = 0.015). 3yDFS for ycT0‐3MRF‐LLN‐ and ycT4/MRF+/LLN+ were 87.5%, 48.0% (p = 0.031) and 3yLR were 0%, 42.8% (p = 0.045). Conclusion NAC yielded a clinically significant effect in about half of high‐risk LARC patients. If NAC alone is ineffective, radiotherapy should be added, even if extended surgery is intended. We report the short/mid‐term results of surgery for high‐risk locally advanced rectal cancer (LARC) after neoadjuvant chemotherapy (NAC, four courses of S‐1 + oxaliplatin+ bevacizumab) without radiotherapy with the primary aim of ypT0‐2. NAC yielded a clinically significant effect in about half of high‐risk LARC patients.