Accuracy and long-term effectiveness of established screening modalities and strategies in colorectal cancer screening: An umbrella review

Colorectal cancer (CRC) screening may reduce the disease incidence and mortality. However, there is a lack of comprehensive evaluation of the existing evidence on different screening modalities. We aimed to systematically summarize the diagnostic accuracy and long-term effectiveness of CRC screening. Medline, Embase, and the Cochrane Database of Systematic Reviews were searched from database inception to December 31, 2023. Systematic reviews and meta-analyses of the diagnostic accuracy of colonoscopy, flexible sigmoidoscopy (FS), guaiac-based fecal occult blood test (gFOBT), fecal immunochemical test (FIT), multi-target stool DNA (mt-sDNA) testing, plasma Septin9 methylation (mSEPT9), computed tomography colonography (CTC) using colonoscopy as the reference standard, or evaluating the long-term effectiveness of incidence and mortality of CRC screening strategies were eligible. Combined accuracy and long-term effectiveness were extracted. The level of evidence was evaluated using GRADE. Using colonoscopy as the reference standard, CTC had the highest sensitivity for detecting CRC and precursors, followed by mt-sDNA, FIT, mSEPT9, and gFOBT, all of which had satisfying specificities (>85%). Convincing evidence showed FS screening reduced CRC incidence and CRC-related mortality, and gFOBT screening reduced CRC mortality but not incidence. Moderate evidence suggested colonoscopy and FIT screening were associated with reduced CRC incidence and mortality. CRC screening was not associated with the reduction of all-cause mortality and non-CRC mortality. Strong variations of diagnostic accuracy existed for the established non-invasive CRC screening methods. Consistent evidence demonstrated the effectiveness of screening in preventing CRC-related death, but convincing evidence was restricted to FS and gFOBT.