• Jennifer S Lin, Leslie A Perdue, Nora B Henrikson, Sarah I Bean, and Paula R Blasi.
• Kaiser Permanente Evidence-based Practice Center, Center for Health Research, Kaiser Permanente, Portland, Oregon.
• JAMA. 2021 May 18; 325 (19): 1978-1998.

ImportanceColorectal cancer (CRC) remains a significant cause of morbidity and mortality in the US.ObjectiveTo systematically review the effectiveness, test accuracy, and harms of screening for CRC to inform the US Preventive Services Task Force.Data SourcesMEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant studies published from January 1, 2015, to December 4, 2019; surveillance through March 26, 2021.Study SelectionEnglish-language studies conducted in asymptomatic populations at general risk of CRC.Data Extraction And SynthesisTwo reviewers independently appraised the articles and extracted relevant study data from fair- or good-quality studies. Random-effects meta-analyses were conducted.Main Outcomes And MeasuresColorectal cancer incidence and mortality, test accuracy in detecting cancers or adenomas, and serious adverse events.ResultsThe review included 33 studies (n = 10 776 276) on the effectiveness of screening, 59 (n = 3 491 045) on the test performance of screening tests, and 131 (n = 26 987 366) on the harms of screening. In randomized clinical trials (4 trials, n = 458 002), intention to screen with 1- or 2-time flexible sigmoidoscopy vs no screening was associated with a decrease in CRC-specific mortality (incidence rate ratio, 0.74 [95% CI, 0.68-0.80]). Annual or biennial guaiac fecal occult blood test (gFOBT) vs no screening (5 trials, n = 419 966) was associated with a reduction of CRC-specific mortality after 2 to 9 rounds of screening (relative risk at 19.5 years, 0.91 [95% CI, 0.84-0.98]; relative risk at 30 years, 0.78 [95% CI, 0.65-0.93]). In observational studies, receipt of screening colonoscopy (2 studies, n = 436 927) or fecal immunochemical test (FIT) (1 study, n = 5.4 million) vs no screening was associated with lower risk of CRC incidence or mortality. Nine studies (n = 6497) evaluated the test accuracy of screening computed tomography (CT) colonography, 4 of which also reported the test accuracy of colonoscopy; pooled sensitivity to detect adenomas 6 mm or larger was similar between CT colonography with bowel prep (0.86) and colonoscopy (0.89). In pooled values, commonly evaluated FITs (14 studies, n = 45 403) (sensitivity, 0.74; specificity, 0.94) and stool DNA with FIT (4 studies, n = 12 424) (sensitivity, 0.93; specificity, 0.85) performed better than high-sensitivity gFOBT (2 studies, n = 3503) (sensitivity, 0.50-0.75; specificity, 0.96-0.98) to detect cancers. Serious harms of screening colonoscopy included perforations (3.1/10 000 procedures) and major bleeding (14.6/10 000 procedures). CT colonography may have harms resulting from low-dose ionizing radiation. It is unclear if detection of extracolonic findings on CT colonography is a net benefit or harm.Conclusions And RelevanceThere are several options to screen for colorectal cancer, each with a different level of evidence demonstrating its ability to reduce cancer mortality, its ability to detect cancer or precursor lesions, and its risk of harms.

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