Background: Blood tests are among the latest innovations in colorectal cancer (CRC) screening. Large, representative, prospective studies with colonoscopy as a reference standard provide diagnostic performance estimates of these non-invasive tests. Data suggest that blood test sensitivity may be higher for CRC but lower for advanced adenomas (AA) compared to some stool tests, and that blood tests are more acceptable to patients. We investigate how these differences impact long-term outcomes of blood-based vs. stool-based screening and identify critical adherence thresholds for similar patient benefit.

Methods: A Cancer Intervention and Surveillance Modeling Network (CISNET) model was replicated to compare screening from age 45 to 75 years, using annual FIT (AA sensitivity, CRC sensitivity, specificity: 24%, 74%, 96%), current FIT-DNA every 3 years (42%, 92%, 90%), or blood testing every 3 years. For blood testing, we assumed 74% CRC sensitivity and 90% specificity per minimum U.S. coverage criteria. AA sensitivity was varied at percentage-point increments between 10% (false-positivity rate; i.e., minBT) and 50% (maximally feasible per clinical judgment; i.e., maxBT). Critical adherence was defined as the additional level of relative adherence to blood-based screening required such that LYG would be equivalent compared to stool-based screening.

Results: Among 1000 unscreened U.S. adults, there were an estimated 70.7 lifetime CRC cases and 27.1 CRC deaths. Screening with 100% adherence reduced incidence by 29.8–52.0 cases (42–74%), reduced mortality by 13.5–21.3 deaths (50–79%) (Table) and yielded 156.4–248.8 LYG. FIT was the most efficacious, followed by FIT-DNA and maxBT, and then minBT. Assuming lower published uptake levels for stool testing, minBT would yield equivalent LYG when adherence was +44% higher (relative) vs. FIT-DNA and +59% higher vs. FIT (Figure). This critical adherence level decreased to +1% and +12%, respectively, for maxBT (Figure). A blood test with moderate AA sensitivity of 20% would yield greater LYG when adherence was >23% higher vs. FIT-DNA and >37% higher vs. FIT (Figure).

Conclusions: As a novel noninvasive CRC screening modality, blood tests have potential to improve CRC screening outcomes, especially when patients prefer the modality over existing tests. This finding confirms the adage that ‘the best test is the one that gets done.’

<b>Table</b>. <b>Lifetime outcomes of blood-based <i>vs</i>. stool-based screening at 100% adherence. </b>CRC = Colorectal cancer; minBT = blood test with 10% advanced adenoma sensitivity, maxBT = blood test with 50% advanced adenoma sensitivity, FIT = fecal immunochemical test.

Table. Lifetime outcomes of blood-based vs. stool-based screening at 100% adherence. CRC = Colorectal cancer; minBT = blood test with 10% advanced adenoma sensitivity, maxBT = blood test with 50% advanced adenoma sensitivity, FIT = fecal immunochemical test.

<b>Figure. Critical adherence to blood-based vs. stool-based screening for colorectal cancer at different levels of sensitivity</b>. CRC = colorectal cancer, FIT = fecal immunochemical test, LYG = life-years gained, sDNA-FIT = stool-DNA FIT.

Figure. Critical adherence to blood-based vs. stool-based screening for colorectal cancer at different levels of sensitivity. CRC = colorectal cancer, FIT = fecal immunochemical test, LYG = life-years gained, sDNA-FIT = stool-DNA FIT.

Andrew Piscitello

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