Noninvasive methods show promise for CRC screening

Two noninvasive methods for colorectal cancer (CRC) screening were tested in studies published March 14 by the New England Journal of Medicine.

In one study, funded by Guardant Health, researchers assessed a cell-free DNA blood-based test in 7,861 patients who were eligible for CRC screening and were enrolled at 265 U.S. sites, including primary care and endoscopy centers. The coprimary outcomes were sensitivity for CRC and specificity for advanced neoplasia (CRC or advanced precancerous lesions) versus screening colonoscopy. The secondary outcome was sensitivity for detecting advanced precancerous lesions.

All patients were 45 to 84 years of age at the time of screening. Mean age was 60 years, 53.7% were women, and 78.5% were White. Fifty-four of 65 participants (83.1%) who had CRC on colonoscopy had a positive result on the cell-free DNA test, while 11 (16.9%) had a negative result, for a sensitivity of 83.1% (95% CI, 72.2% to 90.3%). The cell-free DNA test had a sensitivity of 87.5% (95% CI, 75.3% to 94.1%) for stage I, II, or III CRC and 13.2% (95% CI, 11.3% to 15.3%) for advanced precancerous lesions. Specificity was 89.6% (95% CI, 88.8% to 90.3%) for any advanced neoplasia and 89.9% (95% CI, 89.0% to 90.7%) for negative colonoscopy.

The authors concluded that in an average-risk screening population, the cell-free DNA blood-based test had 83% sensitivity for CRC, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions. They called for further evaluation of the test in various clinical settings and noted that any noninvasive strategy for CRC screening will require adherence to both the noninvasive test and diagnostic colonoscopy for those who screen positive.

The second study, funded by Exact Sciences, evaluated a next-generation multitarget stool DNA test that included assessments for DNA molecular markers and hemoglobin level. The study's primary outcomes were the test's sensitivity for CRC and specificity for advanced neoplasia. The study also aimed to quantify the test's sensitivity for advanced precancerous lesions and specificity for non-neoplastic findings or negative colonoscopy and to compare sensitivities for CRC cancer and advanced precancerous lesions between the multitarget stool DNA test and a commercially available fecal immunochemical test (FIT).

Overall, 20,176 asymptomatic adults ages 40 years and older who were undergoing screening colonoscopy at 186 U.S. sites were evaluated. Mean age was 63.0 years, 53.2% were women, and 60.1% were White. Ninety-eight patients had CRC, 2,144 had advanced precancerous lesions, 6,973 had nonadvanced adenomas, and 10,961 had non-neoplastic findings or negative colonoscopy. The next-generation test had a sensitivity of 93.9% (95% CI, 87.1% to 97.7%) for CRC and a specificity of 90.6% (95% CI, 90.1% to 91.0%) for advanced neoplasia. Its sensitivity for advanced precancerous lesions was 43.4% (95% CI, 41.3% to 45.6%), and its specificity for non-neoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2% to 93.1%). FIT had a sensitivity of 67.3% (95% CI, 57.1% to 76.5%) for CRC and 23.3% (95% CI, 21.5% to 25.2%) for advanced precancerous lesions, with a specificity of 94.8% (95% CI, 94.4% to 95.1%) for advanced neoplasia and 95.7% (95% CI, 95.3% to 96.1%) for non-neoplastic findings or negative colonoscopy. There were no adverse events during the study.

The researchers noted that a relatively high proportion of patients who were enrolled in the study had samples that couldn't be evaluated according to the protocol, possibly because the COVID-19 pandemic may have affected access to colonoscopy, among other factors. In addition, the next-generation multitarget stool DNA test was not directly compared with the current stool DNA test. They concluded that the next-generation multitarget stool DNA test had better sensitivity for CRC and for advanced precancerous lesions than FIT but lower specificity for advanced neoplasia (P<0.001 for all comparisons).

An accompanying editorial said that the results of both studies show promise for increasing uptake of CRC screening and noted that while there are multiple tests available, the best one is the one that the patient will complete, and ease of use may help increase adherence. Adherence is also affected by cost-effectiveness and testing interval and varies by age group, the editorialist noted. "It is hoped that these newer tests will increase use and adherence and elevate the percentage of the population undergoing screening in order to reduce deaths from colorectal cancer," he wrote.