Stool DNA Analysis is Cost-Effective for Colorectal Cancer Surveillance in Patients With Ulcerative Colitis

Abstract

Background & Aims Patients with chronic ulcerative colitis are at increased risk for colorectal neoplasia (CRN). Surveillance by white-light endoscopy (WLE) or chromoendoscopy may reduce risk of CRN, but these strategies are underused. Analysis of DNA from stool samples (sDNA) can detect CRN with high levels of sensitivity, but it is not clear if this approach is cost effective. We simulated these strategies for CRN detection to determine which approach is most cost effective. Methods We adapted a previously published Markov model to simulate the clinical course of chronic ulcerative colitis, the incidence of cancer or dysplasia, and costs and benefits of care with 4 surveillance strategies. These strategies were: analysis of sDNA and diagnostic chromoendoscopy for patients with positive results, analysis of sDNA with diagnostic WLE for patients with positive results, chromoendoscopy with targeted collection of biopsies, or WLE with random collection of biopsies. Costs were based on 2014 Medicare reimbursement. The primary outcome was the incremental cost effectiveness ratio (incremental cost/incremental difference in quality-adjusted life years) compared with no surveillance and a willingness to pay threshold of $50,000. Results All strategies fell below the willingness to pay threshold at 2 year intervals. Incremental cost effectiveness ratios were $16,362 per quality-adjusted life year for sDNA analysis with diagnostic chromoendoscopy; $18,643 per quality-adjusted life year for sDNA analysis with diagnostic WLE; $23,830 per quality-adjusted life year for chromoendoscopy alone; and $27,907 per quality-adjusted life year for WLE alone. In sensitivity analyses, sDNA analysis with diagnostic chromoendoscopy was more cost effective than chromoendoscopy alone, up to a cost of $1135 per sDNA test. sDNA analysis remained cost effective at all rates of compliance; when combined with diagnostic chromoendoscopy, this approach was preferred over chromoendoscopy alone, when the specificity of the sDNA test for CRN was above 65%. Conclusion Based on a Markov model, surveillance for CRN is cost effective for patients with chronic ulcerative colitis. Analysis of sDNA with chromoendoscopies for patients with positive results was more cost effective than chromoendoscopy or WLE alone.

Analysis of DNA Methylation at Specific Loci in Stool Samples Detects Colorectal Cancer and High-Grade Dysplasia in Patients With Inflammatory Bowel Disease

“…The specificity estimates from this study are within the range of values required for effectiveness in a surveillance application, as shown in a recent Markov model. 19 Compared with chromoendoscopy with targeted biopsies and white-light colonoscopy with random biopsies, annual or every-other-year sDNA testing was the most cost-effective option. In sensitivity analyses, sDNA would not be the best option if specificity was less than 65%.…”

“…Second, CRC+HGD events would be most critical to detect among highest-risk patients using a stool test in the interval between surveillance colonoscopies or in lower-risk patients in whom an interval stool DNA test could extend surveillance intervals. 18 Third, cost effectiveness of sDNA relative to white light or chromocolonoscopy does not appear to be influenced by sensitivity for detection of low-grade dysplasia (LGD), 19 LGD lesions 1 cm or larger in diameter are at increased risk of progression to cancer 20 and therefore were included as a secondary end point. All stool samples were assayed as a single batch in blinded fashion.…”

Multi-target stool DNA test in the surveillance of inflammatory bowel disease: a cross-sectional cohort study

“…77 Also, the use of sDNA for CRC surveillance in UC has found to be cost efficient. 78 The MT-sDNA panel containing a combination of mutant KRAS, aberrantly methylated bone morphogenetic protein 3 (BMP3), N-Myc downstream-regulated gene 4 (NDRG4) and a fecal immunochemical test (FIT) for human haemoglobin, detects CRC and screening relevant adenomas with good discrimination in individuals with average risk of developing non CA-CRC. 79 This panel is available for the screening of non CA-CRC in the United States.…”