KRAS mutation is predictive for poor prognosis in rectal cancer patients with neoadjuvant chemoradiotherapy: a systemic review and meta-analysis

To investigate the association between KRAS mutation and prognosis in rectal cancer patients with neoadjuvant chemoradiotherapy. Literature was searched in the databases including Cochrane Library, EMBASE (Ovid), and MEDLINE (PubMed) from inception to December 16, 2020. The keywords “rectal cancer” or “rectal carcinoma” or “rectal adenocarcinoma” and “KRAS” and “neoadjuvant” were used for preliminary literature retrieval. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated for the KRAS mutation and clinical outcomes including overall survival (OS), disease-free survival (DFS), pathologic complete remission (pCR), downstaging of T stages and tumor stages, as well as improvements in tumor regression grading (TRG). Publication bias was assessed by the funnel plots. A total of 16 articles were included for eligibility. The total number of patients was 3674 cases, with an incidence of KRAS gene mutation of 36.6% (1346/3674). Meta-analysis showed that the pooled OR for KRAS mutation on OS was 1.33 (95%CI: 113–1.56). Consistently, results also indicated that the KRAS mutant was related to the poor DFS (pooled OR=1.55, 95%CI: 1.19–2.02). However, KRAS mutation is not related to the PCR (pooled OR= 0.71, 95%CI: 0.44–1.14), downstaging in T stages (pooled OR= 0.66, 95%CI: 0.42–1.06), tumor stages (pooled OR= 1.18, 95%CI: 0.78–1.78, I2=12.9%), as well as improvement in TRG grades (pooled OR= 0.84, 95%CI: 0.59–1.20). KRAS mutation is a predictor for the poor prognosis of neoadjuvant chemoradiotherapy in patients with rectal cancer, but it is not related to the responses of tumors after treatment.