Spotlight on newer methods of CRC screening

Several recent studies examined newer methods of screening for colorectal cancer (CRC).

The first study, published as a research letter by JAMA Internal Medicine on Nov. 18, used existing data to compare a multitarget stool DNA test for CRC with fecal immunochemical tests (FIT). Researchers used the BLUE-C study of a next-generation stool DNA test, which included more than 20,000 patients, and the BLITZ study, a screening colonoscopy study from Germany in which more than 10,000 participants all received the same commercial FIT. When researchers used the cutoff recommended by the FIT manufacturer, 17 μg/g, the FIT had lower sensitivity and higher specificity than the DNA test. However, with a cutoff of 11.7 μg/g, specificity and sensitivity were similar between tests. At 10 μg/g, the sensitivity for CRC was 96.5% with the FIT, and its specificity was modestly lower than the DNA test. “Despite the limitation of being an indirect comparison, the findings of this study suggest that lowering the positivity threshold of a high-quality FIT may be a much more economical way to increase sensitivity of noninvasive CRC screening,” concluded the study authors.

An accompanying editorial comment explained that and other limitations and concluded that the study actually showed that the stool DNA test “provides better discrimination than the comparator FIT and is not just a complicated and expensive FIT.” However, the results also “highlight the need for rigorous and valid comparisons of noninvasive CRC screening tests, which require that the tests are compared not just in the same cohort, but on the same specimens (stool or blood) from that cohort,” the editorial said.

Another study, published by Annals of Internal Medicine on Oct. 29, assessed the clinical and economic impacts of newer, blood-based CRC screening tests. It used published data on existing screening options to compare all of them to no screening. It found that the relative rate of CRC was 0.21 with colonoscopy every 10 years, 0.29 with annual FIT, 0.33 with triennial next-generation multitarget stool DNA, 0.32 with FIT-RNA, and 0.58 with the new cell-free blood DNA (cf-bDNA) tests from Guardant Shield and Freenome. The relative rates for CRC death were 0.19, 0.25, 0.28, 0.28, 0.44, and 0.46, respectively. Given that the cf-bDNA test, at a list price of $1,495, costs $89,600 per quality-adjusted life-year gained versus no screening, “alternatives were less costly and more effective,” the study authors said. The study did find that the cf-bDNA test would match FIT's impact on CRC mortality if it increased uptake by 35% while maintaining equal colonoscopy follow-up. “In conclusion, first-generation novel cf-bDNA tests have the potential to decrease meaningfully the incidence and mortality of CRC compared with no screening, but substantially less profoundly than screening colonoscopy or stool tests,” said the study authors. “In clinical settings with multiple CRC screening options, shared decision making should consider all of the attributes of competing strategies, including test performance characteristics and cost, and the need for colonoscopy follow-up after an abnormal noninvasive screening test must be emphasized.”

Finally, a study published by Clinical Gastroenterology and Hepatology on Nov. 5 assessed a two-sample FIT screening strategy in China. It included 246,349 patients invited to complete two-sample FIT between 2007 and 2021. Overall, 61.10% participated in two-sample FIT; 11.29% of those patients had a positive result and 75.41% of those underwent colonoscopy, yielding a detection rate of 0.57%. Median follow-up was 10.58 years. CRC incidence and mortality were relatively similar between participants who had a negative FIT and those who had a positive FIT and colonoscopy but were higher among those who did not complete the FITs. The study authors concluded that two-sample FIT could effectively identify patients at high risk of CRC. They noted that “evidence supporting colonoscopy screening for CRC is primarily drawn from developed countries, highlighting the need for more population-based evidence on the effectiveness of colonoscopy in low- or intermediate-income countries where the incidence and mortality of CRC are increasing” but where providing colonoscopy screening to average-risk populations might be “resource-consuming and intensive.”