Characteristics of a cost-effective blood test for colorectal cancer screening

Abstract

Background: Blood-based biomarker tests can potentially change the landscape of colorectal cancer (CRC) screening. We characterize the conditions under which blood test screening would be as effective and cost-effective as annual fecal immunochemical testing or decennial colonoscopy.

Methods: We used the 3 Cancer Information and Surveillance Modeling Network-Colon models to compare scenarios of no screening, annual fecal immunochemical testing, decennial colonoscopy, and a blood test meeting Centers for Medicare & Medicaid (CMS) coverage criteria (74% CRC sensitivity and 90% specificity). We varied the sensitivity to detect CRC (74%-92%), advanced adenomas (10%-50%), screening interval (1-3 years), and test cost ($25-$500). Primary outcomes included quality-adjusted life-years (QALY) gained from screening and costs for a US average-risk cohort of individuals aged 45 years.

Results: Annual fecal immunochemical testing yielded 125-163 QALY gained per 1000 at a cost of $3811-$5384 per person, whereas colonoscopy yielded 132-177 QALY gained at a cost of $5375-$7031 per person. A blood test with 92% CRC sensitivity and 50% advanced adenoma sensitivity yielded 117-162 QALY gained if used every 3 years and 133-173 QALY gained if used every year but would not be cost-effective if priced above $125 per test. If used every 3 years, a $500 blood test only meeting CMS coverage criteria yielded 83-116 QALY gained at a cost of $8559-$9413 per person.

Conclusion: Blood tests that only meet CMS coverage requirements should not be recommended to patients who would otherwise undergo screening by colonoscopy or fecal immunochemical testing because of lower benefit. Blood tests need higher advanced adenoma sensitivity (above 40%) and lower costs (below $125) to be cost-effective.

Figure 1.

Effectiveness of blood colorectal cancer (CRC) screening tests as a function of sensitivity and interval. Each curve represents projected lifetime benefits per 1000 guideline-adherent individuals aged 45 years for alternative blood-based screening regimens as a function of blood tests’ sensitivity to CRC and advanced adenomas. Horizontal lines represent the projected benefits of annual fecal immunochemical testing and decennial colonoscopy. Noninvasive tests’ sensitivity is modeled as sensitivity to the most advanced lesion in the colon. Outcomes are discounted at 3% per year. All screening regimens start at 45 years and end at 75 years. Panel A presents discounted life-years gained from screening per 1000 individuals aged 45 years. Panel B presents quality-adjusted life-years gained from screening per 1000 individuals aged 45 years. Vertical axes vary across models to facilitate visualization of relative differences. AA = advance adenoma; COL = colonoscopy; FIT = fecal immunochemical testing; LYG = life-years gained; QALYG = quality-adjusted life-years gained.

Figure 2.

Cost-effectiveness frontier for blood tests with varying test performance. The triangle, circle, and square shapes represent the projected performance of no screening, annual fecal immunochemical testing, and decennial colonoscopy in the cost-effectiveness plane. The line connecting fecal immunochemical testing and colonoscopy is the cost-effectiveness frontier (ie, the line connecting all strategies that provide good value for money). Diamond shapes connected by lines represent the performance of blood testing with varying levels of colorectal cancer (CRC) and advanced adenoma sensitivity, with solid lines representing the lower end of the simulated CRC sensitivity range (0.74) and dashed lines representing the higher end of the simulated CRC sensitivity range (0.92). Separate panels present projections from each of the 3 Cancer Information and Surveillance Modeling Network models. AA = advanced adenoma; COL = colonoscopy; FIT = fecal immunochemical testing; QALYG = quality-adjusted life-years gained.

Figure 3.

Blood test net monetary benefit as a function of performance, interval, and costs. Colors estimate the average net monetary benefit of blood tests across models as a function of test (Centers for Medicare & Medicaid Services) cost, sensitivity to advanced adenomas, and test interval. Colorectal cancer (CRC) sensitivity is set at 92% (upper range of the experimental design). Each panel represents 1 blood-based screening interval. White dashed contour lines represent parameter combinations at which the net monetary benefit is constant, and the black dashed line represents the average net monetary benefit of decennial colonoscopy across the 3 models ($15 479 per person). This figure can be used to identify conditions under which blood tests provide equal or superior net monetary benefit relative to decennial colonoscopy (ie, the area under the black dashed line) and to estimate the gap between the net monetary benefit provided by blood-based tests and colonoscopy. For example, a blood-based test that costs $300 and has 10% advanced adenoma sensitivity yields a $10 000 net monetary benefit, which is approximately two-thirds of the net monetary benefit of colonoscopy. Further, a $500 blood test that is used every 3 years will still be approximately $3000 (ie, 20%) short of matching the net monetary benefit of colonoscopy even if it has 50% advanced adenoma sensitivity and 92% CRC sensitivity. For reference, the average net monetary benefit of annual fecal immunochemical testing estimated by the models is $15 815. COL = colonoscopy; NMB = net monetary benefit.