Differential efficacy of screening modalities for colorectal neoplasms: a systematic review and network meta-analysis of randomized controlled trials

Introduction: Colorectal cancer (CRC), being a major global health problem and the second most common cancer, leads to more than 550,000 deaths per year globally. CRC usually arises from precancerous growths called adenomas. The investigations, flexible sigmoidoscopy (FS), and colonoscopy can help in detecting high-risk precancerous growths and malignant tumors. Most invasive and high-risk colorectal tumors cause occult bleeding, which can be detected by fecal immunochemical test (FIT) and guaiac fecal occult blood test (gFOBT). All these methods can be used to detect malignancies and benign colorectal tumors in patients at risk of developing cancer. This network meta-analysis aims to compare the effectiveness of gFOBT, FIT, FS and colonoscopy for the early detection of CRC. Methods: Search was conducted for all randomized controlled trials (RCTs) in relevant databases (1975-2022), assessed the risk of bias, and retrieved data from relevant RCTs. The participants either underwent screening through the above-mentioned techniques or received no screening at all. Participants who did not undergo any screening were tested as a common control for all screening interventions. Primary outcomes were the incidence of CRC, the incidence of high-risk adenoma, all-cause mortality, and CRC-related mortality. Odds ratio (OR) and 95% CI estimates were calculated using the method of Bayesian network meta-analysis. Results: We identified 11 RCTs involving over one million participants. The reported mean age was 61.87 (45-80) years, and the overall gender distribution was balanced between all the comparison arms. The overall mean prospective follow-up was 8.05 (5.5-11) years after the initial screening was performed. FS offered the greatest reduction in CRC findings [OR = 0.733, 95% CI (0.666, 0.807)] when compared to no screening group. Colonoscopy was associated with a higher detection of CRC as the group had an increased number of high-risk patients [OR = 2.28; 95% CI (1.95, 2.67)]. Biennial FIT is associated with the lowest risk of high-risk adenoma detection [OR = 0.293; 95% CI (0.259,0.330)]. Annual gFOBT is associated with the greatest reduction in the risk of CRC-related mortality [OR 0.757; 95% CI (0.584, 0.977)]. FS is associated with the greatest reduction in the risk of all-cause mortality compared to the no-screening group [OR 0.801; 95% CI (0.772, 0.832)]. Conclusion: Colonoscopy is the most effective screening technique in detecting the incidence of CRC and as well as the incidence of CRC-related mortality. Biennial gFOBT is the most effective non-invasive test and significantly detects the greatest risk of high-risk adenoma development. Sigmoidoscopy is associated with the lowest risk of an all-cause mortality.