Analysis of the effectiveness of two noninvasive fecal tests used to screen for colorectal cancer in average-risk adults

Objectives: Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. Although a significant proportion of CRC cases and deaths are preventable by screening, the morbidity and mortality from CRC remains high and is attributed to suboptimal screening rates. Low levels of population CRC screening uptake may be due to reluctance toward invasiveness of some screening tests, embarrassment, exposure to anesthesia, and grueling preparation, especially for the invasive screening tests. Noninvasive tests overcome many of these barriers because they are more convenient and potentially more attractive to patients compared to invasive tests. This study uses Markov cohort simulation model developed with the help of TreeAge pro software to compare two noninvasive fecal CRC screens, fecal immunohistochemical test (FIT) and multitarget stool DNA test (Mts-DNA) with no screening in order to identify the more effective noninvasive fecal test to screen for colorectal cancer in average-risk adults. Study design: Simulation study developed with Markov model using TreeAge pro software, which included a hypothetical cohort at the average risk of developing colorectal cancer. Methods: Markov model was used to compare population-level CRC-related cases and deaths averted, life-years gained (LYG), and colonoscopies required for two noninvasive CRC screening strategies compared with no screening: annual fecal immunohistochemical testing (FIT) and 3-yearly multitarget stool DNA testing (Mt-sDNA). The model simulated the natural history of the adenoma-carcinoma sequence in average-risk persons starting at age 50 years, and natural history parameters were estimated from the literature and via verification to data on precancerous lesions (i.e. adenomas) and CRC incidence. Screening strategies were then superimposed on the natural history component of the model, allowing for precancerous lesions to be detected and removed, or CRC to be detected and treated at a potentially earlier stage. The sensitivity and specificity for each screen for precancerous lesions and CRC were the performance parameters used to estimate the effectiveness. Results: Annual FIT was more effective than three yearly Mt-sDNA in reducing CRC cases, averting CRC-related deaths, and increasing the LYG compared to no screening. On average, annual FIT resulted in 3.5 fewer CRC cases, and 2.9 fewer CRC deaths per 1000 persons screened compared to 3-yearly Mt-sDNA. Annual FIT usage resulted in a 0.18 LYG compared to Mt-sDNA, which allowed 0.16 LYG, and an annual FIT screening led to a total of 203 more colonoscopies performed compared to Mt-sDNA. One-way sensitivity analysis conducted over the sensitivity rates of each screen by type of lesion showed that FIT remained the more effective strategy for all ranges of sensitivity. Threshold analysis results identified the lowest FIT sensitivity value at which Mt-sDNA performed better for conventional high-risk adenomas and CRC detection to be 0.16 and 0.052, respectively. Conclusion: Both the noninvasive screens were effective compared to no screening. Additionally, annual FIT as a first step noninvasive screening test for CRC appears to be more effective compared to three-yearly Mt-sDNA. (C) 2020 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.