Phase II Trial of Neoadjuvant Chemotherapy, Chemoradiotherapy, and Laparoscopic Surgery with Selective Lateral Node Dissection for Poor-Risk Low Rectal Cancer

PurposeThe aim of this study is to evaluate the safety and efficacy of induction modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus bevacizumab followed by S-1-based chemoradiotherapy in magnetic resonance imaging (MRI)-defined poor-risk locally advanced low rectal cancer.Patients and MethodsThis was a prospective phase II trial at a single comprehensive cancer center. The primary endpoint was the pathological complete response (pCR) rate. Eligible patients had clinical stage II-III low rectal adenocarcinoma with any of the following MRI-defined poor-risk features: circumferential resection margin (CRM)<= 1mm, cT4, positive lateral nodes, mesorectal N2 disease, and/or requiring abdominoperineal resection. Patients received six cycles of mFOLFOX6 with 5mg/kg bevacizumab followed by oral S-1 (80mg/m(2)/day on days 1-14 and 22-35) plus radiotherapy (50.4Gy). Surgery was conducted through a laparoscopic approach. Lateral node dissection was selectively added when the patient had enlarged lateral nodes.ResultsA total of 43 patients were enrolled. Grade 3-4 adverse events occurred in nine patients during induction chemotherapy and in five patients during chemoradiotherapy. One patient declined surgery with a clinical complete response. Forty-two patients underwent surgery, and 16 had pCR [37.2%, 95% confidence interval (CI) 24.4-52.1%]. All underwent R0 resection without conversion, including combined resection of adjacent structures (n=14) and lateral node dissection (n=30). Clavien-Dindo grade 3-4 complications occurred in six patients (14.3%). With median follow-up of 52months, six developed recurrences (lung n=5, local n=1; 3-year relapse-free survival 86.0%).ConclusionsThis study achieved a high pCR rate with favorable toxicity and postoperative complications in poor-risk locally advanced low rectal cancer. Multicenter study is warranted to evaluate this regimen.