Fecal immunochemical testing and colonoscopy detected colorectal cancer (CRC) more effectively and cheaply than did multitarget stool DNA testing, based on a Markov model that assumed equal rates of participation in the three strategies, according to a report in the September issue of Gastroenterology.
Multitarget stool DNA testing (MT-sDNA) “may be a cost-effective alternative if it can achieve patient participation rates that are high enough compared with those of FIT [fecal immunochemical testing] that paying for its higher test cost can be justified,” wrote Uri Ladabaum, MD, and Ajitha Mannalithara, PhD, of Stanford (Calif.) University.
Studies have yielded mixed results about whether FIT or fecal DNA testing are preferable for CRC detection. In one recent large prospective study of patients at average CRC risk, a MT-sDNA test that included KRAS mutations, aberrant NDRG4 and BMP3 methylation, and hemoglobin outperformed FIT for detecting CRC and precancerous lesions but also yielded more false positives, the researchers noted.
Although many decision analyses have examined the efficacy and cost of CRC screening strategies, they have not delved into “the complex patterns of screening participation over time that are now being described (consistent screeners, late entrants, dropouts, intermittent screeners, consistent non-responders),” accounted for variable participation in organized and opportunistic screening programs, or controlled for differential reimbursement rates for public versus private insurance, they added (Gastroenterology 2016 Jun 7. doi: 10.1053/j.gastro.2016.06.003).
Dr. Ladabaum and Dr. Mannalithara therefore constructed a Markov model of patients at average risk for CRC to compare the efficacy and costs of MT-sDNA, colonoscopy, and FIT. The model included numerous variables, such as disease states ranging from a small adenomatous polyp to disseminated CRC, longitudinal changes in rates of participation for both opportunistic screening and organized screening programs, and different rates of commercial and Medicare reimbursement.
Assuming optimal adherence, an annual FIT test and colonoscopy every 10 years were more effective and less costly than MT-sDNA every 3 years, the researchers found. Compared with successful FIT screening programs – which have a 50% rate of consistent participation and a 27% rate of intermittent participation and cost about $153 per patient per testing cycle – an MT-sDNA program would need to have at least a 68% rate of consistent participation and a 32% rate of intermittent (every 3 years) participation, or would need to cost 60% less than it does now ($260 for commercial payment and $197 for Medicare payment in 2015) to be preferable when assuming a threshold of $100,000 for every extra quality-adjusted life year (QALY) gained. MT-sDNA every 3 years, however, would be more cost-effective than opportunistic FIT screening if participation rates were more than 1.7 times those that are typical of opportunistic FIT (15% consistent participation and 30% intermittent participation).
These results held up in various subgroup analyses, and FIT was preferred in 99% of iterations in a Monte Carlo simulation that assumed equal participation rates and the same $100,000 per QALY threshold. “For the MT-sDNA test to be cost-effective, the patient support program included in its cost would need to achieve substantially higher participation rates than those of FIT, whether in organized programs or under the opportunistic screening setting more common in the U.S. than in the rest of the world,” they concluded.
The study was funded by an unrestricted research grant from Exact Science Corp. Dr. Ladabaum reported consulting for ESC in 2014 and disclosed current consulting or advisory relationships with Given Imaging and Mauna Kea Technologies. Dr. Mannalithara had no disclosures.