Performance evaluation of stool DNA methylation tests in colorectal cancer screening: a systematic review and meta‐analysis

Abstract

Aim There is not sufficient evidence about whether stool DNA methylation tests allow prioritizing patients to colonoscopy. Due to the COVID‐19 pandemic, there will be a wait‐list for rescheduling colonoscopies once the mitigation is lifted. The aim of this meta‐analysis was to evaluate the accuracy of stool DNA methylation tests in detecting colorectal cancer. Methods The PubMed, Cochrane Library and MEDLINE via Ovid were searched. Studies reporting the accuracy (Sackett phase 2 or 3) of stool DNA methylation tests to detect sporadic colorectal cancer were included. The DerSimonian–Laird method with random‐effects model was utilized for meta‐analysis. Results Forty‐six studies totaling 16 149 patients were included in the meta‐analysis. The pooled sensitivity and specificity of all single genes and combinations was 62.7% (57.7%, 67.4%) and 91% (89.5%, 92.2%), respectively. Combinations of genes provided higher sensitivity compared to single genes (80.8% [75.1%, 85.4%] vs. 57.8% [52.3%, 63.1%]) with no significant decrease in specificity (87.8% [84.1%, 90.7%] vs. 92.1% [90.4%, 93.5%]). The most accurate single gene was found to be SDC2 with a sensitivity of 83.1% (72.6%, 90.2%) and a specificity of 91.2% (88.6%, 93.2%). Conclusions Stool DNA methylation tests have high specificity (92%) with relatively lower sensitivity (81%). Combining genes increases sensitivity compared to single gene tests. The single most accurate gene is SDC2, which should be considered for further research.

Detection of Postcolonoscopy Colorectal Neoplasia by Multi-target Stool DNA

“…Because no cancers were observed ≤5 years after previous negative screening colonoscopy, and the rates of advanced adenoma ≤5 years were the same as seen 6–9 years after colonoscopy, we propose that mt-sDNA be studied in the future as an interval screening test 5 years after negative screening colonoscopy with or without comparison to FIT. Although not yet available in the United States, there are other methylated stool-based tests in development ( 42 ) and in commercial use ( 43 , 44 ). Although these tests will require validation and approval in the United States, prospective comparison between the stool-based tests with concurrent colonoscopy will be invaluable for assessing differences in test performance and potential use as an adjunct to colonoscopy.…”

Novel Diagnostic Biomarkers in Colorectal Cancer

“…There are several meta-analyses assessing the diagnostic value of stool DNA testing [ 343 , 344 , 345 , 346 , 347 , 348 ]. Zhai et al reported the pooled sensitivities for single- and multiple-gene stool DNA (methylation and mutation) tests in CRC to be 48.0% and 77.8%, respectively, and the pooled specificity for single- and multiple-gene assays to be 97.0% and 92.7%, respectively [ 344 ].…”

“…In Mojtabanezhads et al‘s meta-analysis, this method was shown to have a lower efficiency than reported in previous meta-analyses: the sensitivity for CRC and adenomas was 56.5% and 32.6%, respectively, and the specificity was 93.2% for CRC and adenomas [ 347 ]. In a published meta-analysis including results obtained for over 16,000 patients, it was revealed that the sensitivity of the stool methylation test with a single SDC2 gene was 83.1% and specificity was 91.2%, what is promising in case of this diagnostic method as employed instead of colonoscopy [ 348 ].…”

“…Analysis of results from over 16,000 patients revealed that the sensitivity of the stool methylation test with the single SDC2 gene was 83.1% and that the specificity was 91.2%, showing it to be a promising diagnostic method instead of colonoscopy [ 348 ].…”

Diagnostic accuracy of DNA-based SDC2 methylation test in colorectal cancer screening: a meta-analysis

“…Although previous meta-analyses [ 36 ] and systematic reviews [ 37 ] have analyzed and evaluated SDC2 methylation derived from feces and blood, respectively, for colorectal cancer screening, they included a small number of articles and lacked specific study analysis of SDC2 methylation. Our study was the first meta-analysis to investigate the performance of SDC2 methylation for colorectal cancer screening.…”