ObjectiveTo systematically evaluate whether primary tumor resection (PTR) has a statistical survival benefit as compared with chemotherapy alone (CTA) for asymptomatic stage Ⅳ colorectal cancer patients with unresectable synchronous metastasis (ACRCUSR). MethodsThe PubMed, Embase, Web of Science, Cochrane Central, CNKI, Wanfang, and the other databases were searched systematically and the prospective or retrospective controlled studies of PTR versus CTA in treatment of ACRCUSR were collected. The outcomes included overall survival (OS) and overall 1–5-year survival rates. The Stata 12.0 and RevMan 5.3 softwares were used for the pooled-analysis of relative risk (RR) and hazard ratio (HR). The trial sequential analysis (TSA) software was used to analyze overall 5-year survival rate and calculate the sample size required to achieve stable results. ResultsA total of 35 studies involving 258 478 patients were included. The results of pooled-analysis showed that the OS of ACRCUSR with PTR was statistically better than that with CTA [HR=0.57, 95%CI (0.52, 0.61), P<0.001]; Meanwhile, it was found that the overall survival rates at 1-, 2-, 3-, 4-, and 5-year of ACRCUSR with PTR were statistically better than those with CTA [1-year: RR=1.30, 95%CI (1.21, 1.40), P<0.001; 2-year: RR=1.78, 95%CI (1.64, 1.93), P<0.001; 3-year: RR=2.10, 95%CI (1.65, 2.68), P<0.001; 4-year: RR=3.05, 95%CI (2.07, 3.44), P<0.001; 5-year: RR=3.43, 95%CI (3.00, 3.92), P<0.001]. The TSA showed the reliable outcome at overall 5-year survival rate and the sample size required to achieve stable result was 96 662 cases. ConclusionFrom analysis results of this study, for ACRCUSR with PTR can benefit survival as compared with CTA, which still needs to be verified by more randomized controlled trials.