Development of new non-invasive tests for colorectal cancer screening: the relevance of information on adenoma detection

Abstract

Researchers are actively pursuing the development of a new non-invasive test (NIT) for colorectal cancer (CRC) screening as an alternative to fecal occult blood tests (FOBTs). The majority of pilot studies focus on the detection of invasive CRC rather than precursor lesions (i.e., adenomas). We aimed to explore the relevance of adenoma detection for the viability of an NIT for CRC screening by considering a hypothetical test that does not detect adenomas beyond chance. We used the Simulation Model of Colorectal Cancer (SimCRC) to estimate the effectiveness of CRC screening and the lifetime costs (payers' perspective) for a cohort of US 50-years-old persons to whom CRC screening is offered from age 50-75. We compared annual screening with guaiac and immunochemical FOBTs (with sensitivities up to 70 and 24% for CRC and adenomas, respectively) to annual screening with a hypothetical NIT (sensitivity of 90% for CRC, no detection of adenomas beyond chance, specificity and cost similar to FOBTs). Screening with the NIT was not more effective, but was 29-44% more costly than screening with FOBTs. The findings were robust to varying the screening interval, the NIT's sensitivity for CRC, adherence rates favoring the NIT, and the NIT's unit cost. A comparative modelling approach using a model that assumes a shorter adenoma dwell time (MISCAN-COLON) confirmed the superiority of the immunochemical FOBT over an NIT with no ability to detect adenomas. Information on adenoma detection is crucial to determine whether a new NIT is a viable alternative to FOBTs for CRC screening. Current evidence thus lacks an important piece of information to identify marker candidates that hold real promise and deserve further (large-scale) evaluation.

Keywords: blood test; colorectal cancer; screening; stool test.

Figure 1

Results of the search of the MEDLINE database for studies published between January 2009 and January 2013 using the search terms “colorectal neoplasm” and “stool marker” (A) or “blood marker” (B).^{a a}When reviewing the studies, we focused on whether or not information on sensitivity for adenomas is provided, but did not aim for reporting and comparing the diagnostic performance of the various markers. To adequately address the latter, a careful consideration of the heterogeneously designed studies would have been required, which was beyond the scope of this manuscript. The references of studies reporting on sensitivity for adenomas are listed in the Supplement.

Figure 2

Illustration of the model structure: A cohort was simulated from birth to death. A certain proportion of the population develops one or more stepwise growing adenomas during life, of which a minority progresses to colorectal cancer (CRC). A certain proportion of adenomas and preclinical CRCs may be detected through screening, depending on the sensitivity of the screening test.

Figure 3

Discounted life-years gained compared with no screening and discounted lifetime costs for the Hemoccult II strategy, the fecal immunochemical test (FIT) strategy and the new test strategy: Results of the base-case analysis and results of the sensitivity analysis for this scenario lowering the new test’s unit cost to zero.

Figure 4

Figure 4A. Discounted life-years gained compared with no screening and discounted lifetime costs for the Hemoccult II strategy, the fecal immunochemical test (FIT) strategy and the new test strategy: Results of the sensitivity analysis using best case test performance estimates for the new test and worst case test performance estimates for Hemoccult II and FIT, and results of the sensitivity analysis for this scenario lowering the new test’s unit cost to zero. Figure 4B. Discounted life-years gained compared with no screening and discounted lifetime costs for the Hemoccult II strategy, the fecal immunochemical test (FIT) strategy and the new test strategy: Results of the sensitivity analysis assuming an adherence rate of 80% for the new test strategy and an adherence rate of 50% for the Hemoccult II and the FIT strategy, and results of the sensitivity analysis for this scenario lowering the new test’s unit cost to zero.

Figure 4

Figure 4A. Discounted life-years gained compared with no screening and discounted lifetime costs for the Hemoccult II strategy, the fecal immunochemical test (FIT) strategy and the new test strategy: Results of the sensitivity analysis using best case test performance estimates for the new test and worst case test performance estimates for Hemoccult II and FIT, and results of the sensitivity analysis for this scenario lowering the new test’s unit cost to zero. Figure 4B. Discounted life-years gained compared with no screening and discounted lifetime costs for the Hemoccult II strategy, the fecal immunochemical test (FIT) strategy and the new test strategy: Results of the sensitivity analysis assuming an adherence rate of 80% for the new test strategy and an adherence rate of 50% for the Hemoccult II and the FIT strategy, and results of the sensitivity analysis for this scenario lowering the new test’s unit cost to zero.