Randomized Trial of Facilitated Adherence to Screening-Colonoscopy Versus Sequential Fecal-Based Blood Test.

BACKGROUND AND AIMS: Colorectal cancer (CRC) screening guidelines include screening-colonoscopy and sequential high sensitivity fecal occult blood testing (HSgFOBT), with expectation of similar effectiveness based on the assumption of similar high adherence. However, adherence to screening-colonoscopy compared to sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening-colonoscopy versus sequential and non-sequential HSgFOBT.

METHODS: Participants aged 40-69 were enrolled in three centers, which represented different clinical settings. Participants were randomized into a single screening-colonoscopy arm versus sequential HSgFOBT arm comprised of 4-7 rounds. Initial adherence to screening-colonoscopy and sequential adherence to HSgFOBT, follow-up colonoscopy for positive HSgFOBT tests, crossover to colonoscopy, and detection of advanced neoplasia or large serrated lesions (ADN-SER) were measured.

RESULTS: 3,523 participants were included in the trial with 1761 and 1762 participants randomized to the screening-colonoscopy and HSgFOBT arms, respectively. Adherence was 1473 (83.6%) for the screening-colonoscopy arm versus 1288 (73.1%) for the HSgFOBT arm after one round (RR=1.14, [95% CI 1.10-1.19] P ≤0.001), but only 674 (38.3%) over four sequential HSgFOBT rounds (RR=2.19, [95% CI 2.05-2.33]). Overall adherence to any screening increased to 1558 (88.5%) in the screening-colonoscopy arm during the entire study period and 1493 in the HSgFOBT arm (84.7%) (RR=1.04, [95% CI 1.02-1.07]). 436 (24.7%) participants crossed over to screening-colonoscopy over the first four rounds. ADN-SER were detected in 121 (8.2%) of the 1473 participants in the colonoscopy arm who were adherent to protocol in the first 12 months of the study, whereas the detection of ADN-SER among those who were not sequentially adherent (N=709) to HSgFOBT was subpar (0.6%) (RR=14.72, [95% CI 5.46-39.67]) when compared to those who were sequentially adherent (3.3%) (N=647) (RR=2.52, [95% CI 1.61-3.98]) to HSgFOBT in the first four rounds. When including colonoscopies from HSgFOBT patients who were never positive yet crossed over (N=1483), 5.5% of ADN-SER were detected (RR=1.50, [95% CI 1.15-1.96]) in the first four rounds.

CONCLUSIONS: Observed adherence to sequential rounds of HSgFOBT was suboptimal when compared to a single screening-colonoscopy. The detection of ADN-SER was inferior when non-sequential HSgFOBT adherence was compared to sequential adherence. However, the greatest number of ADN-SER was detected among those who crossed over to colonoscopy and opted to receive a colonoscopy. The effectiveness of a HSgFOBT screening program may be enhanced if crossover to screening-colonoscopy is permitted.