Neoadjuvant Chemotherapy Followed by Surgery Versus Surgery Alone for Colorectal Cancer: Meta-analysis of Randomized Controlled Trials

Effects of neoadjuvant chemotherapy (NAC) on colorectal cancer (CRC) have been largely studied, while its survival and surgical benefits remain controversial. This study aimed to perform a meta-analysis of randomized controlled trials (RCTs), comparing efficacy and safety of NAC plus surgery with surgery alone (SA) for CRC. We searched systematically databases of MEDLINE, EMBASE, and the Cochrane Library for RCTs comparing NAC and surgery with SA for treating CRC. References of relevant articles and reviews, conference proceedings, and ongoing trial databases were also screened. Primary outcomes included overall and disease-free survivals, total and perioperative mortalities, recurrence, and metastasis. Meta-analysis was performed where possible comparing parameters using relative risks (RRs). Safely analysis was then performed. Outcomes for stages II and III tumors were also meta-analyzed, respectively. Our study was conducted according to intention-to-treat analysis. A total of 6 RCTs comparing NAC (n = 1393) with SA (n = 1358) published from 2002 to 2012 were identified. Compared with SA, NAC tended to reduce overall recurrences (21.86% vs 25.15%, RR: 0.70, 95% confidence interval [CI]: 0.32–1.56, P = 0.09), and prevent vascular invasion (32.30% vs 43.12%, RR: 0.73, 95% CI: 0.53–1.00, P = 0.05); and significantly lowered distant metastasis (15.58% vs 23.80%, RR: 0.66, 95% CI: 0.50–0.86, P = 0.002), especially liver metastasis rate (13.00% vs 18.25%, RR: 0.71, 95% CI: 0.51–0.99, P = 0.04), and associated with higher incidence of ypT0-2 cases upon resection (13.04% vs 6.42%, RR: 2.36, 95% CI: 1.02–5.44, P = 0.04). All other parameters were comparable. NAC-related side-effects were generally mild. NAC mainly benefited patients with stage III disease. NAC could prevent recurrence and metastasis, associates with better tumor stages upon resection, and potentially impedes vascular invasion among CRC patients. NAC does not contribute to significant survival benefits for CRC, and compares favorably with SA in tumor-free resection rates, nodal status upon resection, and postsurgical complications. This level 1a evidence does not support NAC to obviously outweigh SA in terms of survival and surgical benefits for CRC currently.