Background: Noninvasive tests for colorectal cancer (CRC) screening and prevention limit the need for invasive colonoscopy to follow-up positive test results. However, the relative performance characteristics of available noninvasive tests have not yet been adequately compared. Objective: To perform a systematic review and meta-analysis to compare the diagnostic performance of the available noninvasive CRC screening tests, including multi-target stool-DNA (mt-sDNA), fecal immunochemical test (FIT), and CT colonography (CTC), with emphasis on comparison of PPV and detection rate (DR) for advanced neoplasia (AN, encompassing advanced adenomas and CRC). Evidence Acquisition: After systematic search of MEDLINE and Google Scholar, 10 mt-sDNA, 27 CTC, and 88 FIT published screening studies involving 25,132, 33,493, and 2,355,958 asymptomatic adults, respectively, were included. Meta-analysis with hierarchical Bayesian modeling was conducted in accordance with Cochrane Collaboration and PRISMA guidelines to determine test-positivity rates (TPR) leading to optical colonoscopy, as well as PPV and DR for both AN and CRC. Different positivity thresholds were considered for FIT and CTC. Evidence Synthesis: Point estimates (with 95% credible intervals) from pooled Bayesian meta-analysis were as follows [combining all thresholds for FIT and stratifying CTC by ≥6mm (CTC6) and ≥10mm (CTC10) thresholds]: TPR for mt-sDNA=13.5% (9.5-16.6%), FIT=6.4% (5.8-7.2%), CTC6=13.4% (11.4-15.6%), and CTC10=6.6% (5.2-7.7%); AN-PPV for mt-sDNA=26.9% (21.8-33.1%), FIT=31.8% (29.3-34.5%), CTC6=34.4% (27.2-41.0%), and CTC10=61.0% (54.0-70.0%); CRC-PPV for mt-SDNA=2.4% (1.5-3.9%), FIT=4.9% (4.3-5.3%), CTC6=3.5% (2.5-4.8%), and CTC10=6.0% (4.7-8.8%); and AN-DR for mt-SDNA=3.4% (2.5-4.8%), FIT=2.0% (1.8-2.3%), CTC6=4.8% (4.0-6.5%), and CTC10=4.0% (3.0-4.6%). When FIT is restricted to a lower threshold (<10 μg), its performance profile is similar to mt-sDNA, though available data are limited. AN-PPV odds ratios (relative to CTC10 as reference) were 0.24 (0.17-0.33) for mt-sDNA, 0.33 (0.24-0.43) for FIT, and 0.33 (0.25-0.47) for CTC6. Conclusion: Among noninvasive CRC screening tests, CTC with ≥10 mm threshold most effectively targets AN, preserving detection while also decreasing unnecessary colonoscopies compared with mt-sDNA and FIT. Clinical Impact: CTC performed with a polyp size threshold for colonoscopy referral set at ≥10 mm represents the most effective and efficient non-invasive screening test for CRC prevention and detection.
PPV and Detection Rate of mt-sDNA, FIT, and CT Colonography for Advanced Neoplasia: A Hierarchical Bayesian Meta-Analysis of the Noninvasive Colorectal Screening Tests
Hassan C
2021-01-01
Abstract
Background: Noninvasive tests for colorectal cancer (CRC) screening and prevention limit the need for invasive colonoscopy to follow-up positive test results. However, the relative performance characteristics of available noninvasive tests have not yet been adequately compared. Objective: To perform a systematic review and meta-analysis to compare the diagnostic performance of the available noninvasive CRC screening tests, including multi-target stool-DNA (mt-sDNA), fecal immunochemical test (FIT), and CT colonography (CTC), with emphasis on comparison of PPV and detection rate (DR) for advanced neoplasia (AN, encompassing advanced adenomas and CRC). Evidence Acquisition: After systematic search of MEDLINE and Google Scholar, 10 mt-sDNA, 27 CTC, and 88 FIT published screening studies involving 25,132, 33,493, and 2,355,958 asymptomatic adults, respectively, were included. Meta-analysis with hierarchical Bayesian modeling was conducted in accordance with Cochrane Collaboration and PRISMA guidelines to determine test-positivity rates (TPR) leading to optical colonoscopy, as well as PPV and DR for both AN and CRC. Different positivity thresholds were considered for FIT and CTC. Evidence Synthesis: Point estimates (with 95% credible intervals) from pooled Bayesian meta-analysis were as follows [combining all thresholds for FIT and stratifying CTC by ≥6mm (CTC6) and ≥10mm (CTC10) thresholds]: TPR for mt-sDNA=13.5% (9.5-16.6%), FIT=6.4% (5.8-7.2%), CTC6=13.4% (11.4-15.6%), and CTC10=6.6% (5.2-7.7%); AN-PPV for mt-sDNA=26.9% (21.8-33.1%), FIT=31.8% (29.3-34.5%), CTC6=34.4% (27.2-41.0%), and CTC10=61.0% (54.0-70.0%); CRC-PPV for mt-SDNA=2.4% (1.5-3.9%), FIT=4.9% (4.3-5.3%), CTC6=3.5% (2.5-4.8%), and CTC10=6.0% (4.7-8.8%); and AN-DR for mt-SDNA=3.4% (2.5-4.8%), FIT=2.0% (1.8-2.3%), CTC6=4.8% (4.0-6.5%), and CTC10=4.0% (3.0-4.6%). When FIT is restricted to a lower threshold (<10 μg), its performance profile is similar to mt-sDNA, though available data are limited. AN-PPV odds ratios (relative to CTC10 as reference) were 0.24 (0.17-0.33) for mt-sDNA, 0.33 (0.24-0.43) for FIT, and 0.33 (0.25-0.47) for CTC6. Conclusion: Among noninvasive CRC screening tests, CTC with ≥10 mm threshold most effectively targets AN, preserving detection while also decreasing unnecessary colonoscopies compared with mt-sDNA and FIT. Clinical Impact: CTC performed with a polyp size threshold for colonoscopy referral set at ≥10 mm represents the most effective and efficient non-invasive screening test for CRC prevention and detection.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
