Abstract
OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. Colonoscopy (CO) is the gold standard for screening, but its invasive nature and low adherence limit its use. Second-generation capsule endoscopy (CCE-2) emerges as a non-invasive alternative. This study aimed to evaluate the diagnostic accuracy of CCE-2 in detecting colorectal polyps, using CO as the reference standard. METHODS: A systematic review and meta-analysis of prospective studies in adults undergoing CCE-2 followed by CO was performed. Searches were conducted in PubMed, EMBASE and Cochrane up to May 2025. Diagnostic accuracy metrics were pooled using a Bayesian bivariate model with construction of HSROC curves. To assess clinical impact, a fictitious cohort of 1000 patients was simulated based on polyp prevalence and submitted to decision curve analysis (DCA). RESULTS: Twelve studies including 4316 patients were analysed. CCE-2 demonstrated sensitivity/specificity of 0.89/0.94 for polyps ≥6 mm and 0.91/0.98 for ≥10 mm. In FIT-positive patients, performance was superior. In the simulated cohort, CCE-2 showed greater net benefit from a 20% pre-test probability threshold of a patient to have a polyp of any size, surpassing the universal CO strategy, avoiding unnecessary colonoscopies to make this diagnostic. CONCLUSION: CCE-2 is a non-invasive, safe and accurate alternative for CRC screening, with potential to increase adherence, particularly in patients with contraindications or refusal of CO. However, the lack of therapeutic capability and absence of evidence regarding mortality reduction limit its role as a first-line tool. Randomized clinical trials are needed to consolidate its role in personalized screening.