Surgery with versus without preoperative concurrent chemoradiotherapy for mid/low rectal cancer: an interim analysis of a prospective, randomized trial

Abstract

IntroductionMultimodality therapy, including preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME), has effectively reduced local recurrence rates of rectal cancer over the past decade. However, the benefits and risks of the addition of neoadjuvant CRT to surgery need to be evaluated. This study was to compare the efficacy of TME with versus without preoperative concurrent chemoradiotherapy (CCRT) involving XELOX regimen (oxaliplatin plus capecitabine) in Chinese patients with stages II and III mid/low rectal adenocarcinoma.MethodsWe randomly assigned patients to the TME group (TME without preoperative CCRT) or CCRT + TME group (TME with preoperative CCRT). The primary endpoint was disease-free survival (DFS); the secondary endpoints were overall survival (OS), local and distant recurrence, tumor response to CRT, toxicity, sphincter preservation, and surgical complications. An interim analysis of the potential inferiority of DFS in the CCRT + TME group was planned when the first 180 patients had been followed up for at least 6 months.ResultsA total of 94 patients in the TME group and 90 patients in the CCRT + TME group were able to be evaluated. The 3-year DFS and OS rates were 86.3 % and 91.5 % in the whole cohort, respectively. The 3-year DFS rates of the TME and CCRT + TME groups were 85.7% and 87.9 % (P = 0.766), respectively, and the 3-year OS rates were 90.7 % and 92.3 % (P = 0.855), respectively. The functional sphincter preservation rates of the TME and CCRT + TME groups were 71.3 % and 70.0 % (P = 0.849), respectively. In the TME group, 16 (17.0 %) patients were proven to have pTNM stage I disease after surgery. In the CCRT + TME group, 32 (35.6 %) patients achieved a pathologic complete response (pCR).ConclusionsPreliminary results indicated no significant differences in the DFS, OS, or functional sphincter preservation rates between the TME and CCRT + TME groups. However, preoperative CCRT with XELOX yielded a high pCR rate. Newer techniques are needed to improve the staging accuracy, and further investigation is warranted.Clinical trial registration numberChi CTR-TRC-08000122

Surgical treatment following neoadjuvant chemoradiotherapy in locally advanced rectal cancer

“…On the basis of the results of a prospective randomized trial, Ngan et al concluded that long‐course neoadjuvant RT may be more effective in reducing LR for distal tumors . In Asian populations, long‐course NCRT remains the favored treatment because it can enable concurrent chemotherapy, improved sphincter preservation, and better tumor regression …”

“…Studies have proposed up‐front surgery for upper rectal tumors because of the low LR risk and the sphincter preservation advantage . In 2017, a multidisciplinary team of European cancer experts achieved consensus on risk‐adapted treatment in those patients with recurring cT4 tumors in the pelvis might benefit from NCRT .…”

“…11 In Asian populations, long-course NCRT remains the favored treatment because it can enable concurrent chemotherapy, improved sphincter preservation, and better tumor regression. 5,[12][13][14][15][16] The optimal regimen of chemotherapeutic agents to be administered concurrently with neoadjuvant RT for rectal cancer is undetermined. In addition, whether the use of more effective chemotherapy improves OS remains unanswered.…”

“…Studies have proposed up-front surgery for upper rectal tumors because of the low LR risk and the sphincter preservation advantage. 15,[28][29][30][31] In 2017, a multidisciplinary team of European cancer experts achieved consensus on risk-adapted treatment in those patients with recurring cT4 tumors in the pelvis might benefit from NCRT. 32 Nevertheless, they did not recommend applying this treatment model uniformly to all rectal cancer patients regardless of tumor location.…”

Neoadjuvant treatments for resectable rectal cancer: A network meta‑analysis

“…Of the 8,178 citations identified via the literature search in the present study, 6,961 citations were retained after removing duplicates and subsequently 6,401 articles were excluded after title and abstract screening, leaving 560 studies for a full-text review. Following exclusion of a further 531 articles which were deemed unsuitable, a total of 23 RCTs with a cumulative sample size of 10,895 patients were included in the review and NMA (7,8,(11)(12)(13)(14)(18)(19)(20)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54); Fig. 1).…”