Predominant serrated molecular signature in postcolonoscopy colorectal cancer: A systematic review and meta-analysis

Introduction: Postcolonoscopy colorectal cancers (PCCRCs) are an adverse outcome associated with missed lesions and incomplete polypectomy. However, their molecular features have not been systematically reviewed. Methods: We searched PubMed, Embase, and Cochrane Library databases from inception to April 2024. Studies examining the molecular characteristics of PCCRCs, including microsatellite instability (MSI), CpG island methylator phenotype (CIMP), genetic mutations, and chromosomal alterations were regarded as eligible. Results: In total, 15 studies encompassing 11 cohorts, with 2,143 PCCRC and 19,036 sporadic colorectal cancer (SCRC) cases, were analyzed. Compared with SCRC, PCCRC was associated with older age (standardized mean difference 0.29, 95% confidence interval [CI] 0.20–0.38) and more proximal lesions (odds ratio [OR] 2.08, 95% CI 1.91–3.63). Molecularly, PCCRCs were more likely to exhibit MSI (OR 2.28, 95% CI 1.69–3.08), CIMP (OR 2.10, 95% CI 1.39–3.18), and BRAF mutations (OR 1.74, 95% CI 1.22–2.49) but were less likely to exhibit KRAS mutations (OR 0.63, 95% CI 0.45–0.87). Furthermore, MSI was strongly correlated with BRAF mutation (OR 9.36, 95% CI 5.11–17.16) and proximal lesions (OR 6.16, 95% CI 3.74–10.16) in a pooled analysis. Although the pooled 5-year overall survival rate was similar between PCCRC and SCRC cases (hazard ratio 1.03, 95% CI 0.64–1.66), PCCRCs exhibited worse survival compared with screening-detected ones (hazard ratio 1.65, 95% CI 1.46–1.86). Conclusion: Clinical and molecular features indicate that PCCRCs are more likely to be associated with the serrated pathway than with SCRC. Enhancing the detection of clinically significant serrated lesions may improve the efficacy of CRC screening.