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

Abstract

Background & 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 with sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening colonoscopy vs sequential and nonsequential HSgFOBTs.

Methods: Participants aged 40-69 years were enrolled at 3 centers representing different clinical settings. Participants were randomized into a single screening colonoscopy arm vs sequential HSgFOBT arm composed 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-SERs) were measured.

Results: There were 3523 participants included in the trial; 1761 and 1762 participants were randomized to the screening colonoscopy and HSgFOBT arms, respectively. Adherence was 1473 (83.6%) for the screening colonoscopy arm vs 1288 (73.1%) for the HSgFOBT arm after 1 round (relative risk [RR], 1.14; 95% CI, 1.10-1.19; P ≤ .001), but only 674 (38.3%) over 4 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 (84.7%) in the HSgFOBT arm (RR, 1.04; 95% CI, 1.02-1.07). Four hundred thirty-six participants (24.7%) crossed over to screening colonoscopy during the first 4 rounds. ADN-SERs were detected in 121 of the 1473 participants (8.2%) in the colonoscopy arm who were adherent to protocol in the first 12 months of the study, whereas detection of ADN-SERs among those who were not sequentially adherent (n = 709) to HSgFOBT was subpar (0.6%) (RR, 14.72; 95% CI, 5.46-39.67) compared with those who were sequentially adherent (3.3%) (n = 647) (RR, 2.52; 95% CI, 1.61-3.98) to HSgFOBT in the first 4 rounds. When including colonoscopies from HSgFOBT patients who were never positive yet crossed over (n = 1483), 5.5% of ADN-SERs were detected (RR, 1.50; 95% CI, 1.15-1.96) in the first 4 rounds.

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

Clinicaltrials: gov, Number: NCT00102011.

Keywords: Colonoscopy; Colorectal Cancer Screening; Crossover Colonoscopy; Fecal Occult Blood Test; Screening Guidelines.

Appendix Figure 1.

Site Locations for National Colonoscopy Study

Appendix Figure 2.

National Colonoscopy Study flowchart by screening round Screening colonoscopy (SCO), High sensitivity guaiac fecal occult blood test (HSgFOBT) 1, 2, 3, 4: Had a colonoscopy and later went on to participate in more screening in some form (i.e. did not discontinue forever), n = 10, 6, 5, 2, respectively 5: 1 patient crossed over in round 4. They did not receive an FOBT kit in round 4.

Appendix Figure 3.

Pathology findings by screening arm for adenomas and advanced neoplasia* without inclusion of serrated polyps High sensitivity fecal occult blood test (HSgFOBT); Relative Risk (RR); 95% Confidence Intervals (95% CI) * Advanced neoplasia defined as lesions with any villous component, high grade dysplasia, or 1 cm or larger, or 3 or more tubular adenomas <1 cm. Colorectal cancer is also included in this category † Screening-colonoscopy pathology findings based on total 1761 participants randomized; 1558 participants with colonoscopies, of which 85 had initial colonoscopy after 12 months. 97.6% of screening-colonoscopy arm participants reached the cecum and 98.0% of colonoscopies were cleared. 95.6% of HSgFOBT-positive colonoscopies participants performed reached the cecum and 97.1% of colonoscopies were cleared. ‡ HSgFOBT findings from follow-up colonoscopy after a positive HSgFOBT and from cross-over colonoscopy without a positive HSgFOBT based on 1762 participants randomized

Appendix Figure 4a:

Adherence proportions by age groups by per-protocol adherence and any adherence High sensitivity fecal occult blood test (HSgFOBT) University of Minnesota (MIN), Kaiser-Permanente Washington State (KPWA), Louisiana State University (LSU)

Appendix Figure 4b:

Adherence proportions by sex by per-protocol adherence and any adherence High sensitivity fecal occult blood test (HSgFOBT) University of Minnesota (MIN), Kaiser-Permanente Washington State (KPWA), Louisiana State University (LSU)

Figure 1:

National Colonoscopy Study flowchart of participant eligibility Screening colonoscopy (SCO), High sensitivity guaiac fecal occult blood test (HSgFOBT), familial adenomatous polyposis (FAP)

Figure 2:

Adherence to screening-colonoscopy versus four rounds of screening for HSgFOBT (per protocol) High sensitivity fecal occult blood test (HSgFOBT); Relative Risk (RR); 95% Confidence Intervals (95% CI) *1473 participants completed per protocol initial screening-colonoscopies defined within <12 months after randomization **92.2% of HSgFOBT positive patients completed their follow-up colonoscopy in the first four rounds

Figure 3:

Adherence to screening-colonoscopy versus adherence to any screening over four screening rounds for HSgFOBT High sensitivity fecal occult blood test (HSgFOBT) Relative Risk (RR); 95% Confidence Intervals (95% CI) *1473 participants completed initial screening-colonoscopies within <12 months after randomization and another 85 completed initial screening-colonoscopies > 12 months after randomization (N=1558) ** 92.2% of HSgFOBT positive patients completed their follow-up colonoscopy in the first four rounds

Figure 4:

Pathology findings by screening arm with adenoma or serrated lesions over 4-7 years followed High sensitivity fecal occult blood test (HSgFOBT); Relative Risk (RR); 95% Confidence Intervals (95% CI) * Serrated polyp definition was based on Rex and Gupta definition on features of serrated lesions which are associated with advanced neoplasia. These features include proximal colon location of serrated lesions, increasing number and larger size of serrated lesions or traditional serrated adenomas histology (Appendix Table 2). † Positive screening-colonoscopy pathology findings based on total 1761 participants randomized; 1558 participants with colonoscopies, of which 85 had initial colonoscopy after 12 months. ‡ HSgFOBT findings from follow-up colonoscopy after a positive HSgFOBT and from cross-over colonoscopy without a positive HSgFOBT based on 1762 participants randomized.

Figure 5:

Colonoscopy and HSgFOBT pathology findings from adherence over the first 4 rounds A) Per-protocol findings for screening-colonoscopy and HSgFOBT, defined as completion of screening-colonoscopy 12 months after randomization or [1] four sequential rounds of negative HSgFOBTs, or [2] participants who had a positive HSgFOBT with proper number of preceding negative and diagnostic colonoscopy after positive HSgFOBT B) Per-protocol findings for screening-colonoscopy and individuals who completed at least 1 but no more than 3 rounds of HSgFOBTs C) Per-protocol findings for screening-colonoscopy and individuals who completed at least 1 but no more than 3 rounds of HSgFOBTs combined with those who sequentially completed all four rounds of HSgFOBT D) Includes all screening in the first four rounds defined as all screening-colonoscopies as well as all HSgFOBT including crossovers