Screening uptake of colonoscopy versus fecal immunochemical testing in first-degree relatives of patients with non-syndromic colorectal cancer: A multicenter, open-label, parallel-group, randomized trial (ParCoFit study).

BACKGROUND: Colonoscopy screening is underused by first-degree relatives (FDRs) of patients with non-syndromic colorectal cancer (CRC) with screening completion rates below 50%. Studies conducted in FDR referred for screening suggest that fecal immunochemical testing (FIT) was not inferior to colonoscopy in terms of diagnostic yield and tumor staging, but screening uptake of FIT has not yet been tested in this population. In this study, we investigated whether the uptake of FIT screening is superior to the uptake of colonoscopy screening in the familial-risk population, with an equivalent effect on CRC detection. METHODS AND FINDINGS: This open-label, parallel-group, randomized trial was conducted in 12 Spanish centers between February 2016 and December 2021. Eligible individuals included asymptomatic FDR of index cases <60 years, siblings or ≥2 FDR with CRC. The primary outcome was to compare screening uptake between colonoscopy and FIT. The secondary outcome was to determine the efficacy of each strategy to detect advanced colorectal neoplasia (adenoma or serrated polyps ≥10 mm, polyps with tubulovillous architecture, high-grade dysplasia, and/or CRC). Screening-naïve FDR were randomized (1:1) to one-time colonoscopy versus annual FIT during 3 consecutive years followed by a work-up colonoscopy in the case of a positive test. Randomization was performed before signing the informed consent using computer-generated allocation algorithm based on stratified block randomization. Multivariable regression analysis was performed by intention-to-screen. On December 31, 2019, when 81% of the estimated sample size was reached, the trial was terminated prematurely after an interim analysis for futility. Study outcomes were further analyzed through 2-year follow-up. The main limitation of this study was the impossibility of collecting information on eligible individuals who declined to participate. A total of 1,790 FDR of 460 index cases were evaluated for inclusion, of whom 870 were assigned to undergo one-time colonoscopy (n = 431) or FIT (n = 439). Of them, 383 (44.0%) attended the appointment and signed the informed consent: 147/431 (34.1%) FDR received colonoscopy-based screening and 158/439 (35.9%) underwent FIT-based screening (odds ratio [OR] 1.08; 95% confidence intervals [CI] [0.82, 1.44], p = 0.564). The detection rate of advanced colorectal neoplasia was significantly higher in the colonoscopy group than in the FIT group (OR 3.64, 95% CI [1.55, 8.53], p = 0.003). Study outcomes did not change throughout follow-up. CONCLUSIONS: In this study, compared to colonoscopy, FIT screening did not improve screening uptake by individuals at high risk of CRC, resulting in less detection of advanced colorectal neoplasia. Further studies are needed to assess how screening uptake could be improved in this high-risk group, including by inclusion in population-based screening programs. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT02567045).

Panchromoendoscopy Increases Detection of Polyps in Patients With Serrated Polyposis Syndrome.

BACKGROUND & AIMS: Serrated polyposis syndrome (SPS), characterized by multiple and/or large proximal serrated lesions, increases the risk of colorectal cancer. Serrated lesions often are missed during colonoscopy but panchromoendoscopy can increase their detection in an average-risk population. We performed a randomized controlled study to determine the efficacy of panchromoendoscopy in detection of polyps in patients with SPS. METHODS: Patients with SPS (n = 86 patients) underwent tandem high-definition (HD) colonoscopies from February 2015 through July 2016 at 7 centers in Spain. Patients were assigned randomly to groups that received 2 HD white-light endoscopy examinations (HD-WLE group; n = 43) or HD-WLE followed by 0.4% indigo carmine panchromoendoscopy (HD-CE group; n = 43). For each procedure, polyps detected were described, removed, and analyzed by histology. The primary outcome was additional polyp detection rate, defined as the number of polyps detected during the second inspection divided by the total number of polyps detected during the first and the second examination. RESULTS: A total of 774 polyps were detected (362 in the HD-WLE group and 412 in the HD-CE group); 54.2% were hyperplastic, 13.8% were adenomas, and 10.9% were sessile serrated polyps. There was a significantly higher additional polyp detection rate in the HD-CE group (0.39; 95% CI, 0.35-0.44) than in the HD-WLE group (0.22; 95% CI, 0.18-0.27) (P < .001). A higher additional rate of serrated lesions proximal to the sigmoid colon were detected in the second inspection with HD-CE (0.40; 95% CI, 0.33-0.47) than with HD-WLE (0.24; 95% CI, 0.19-0.31) (P = .001). Detection of adenomas and serrated lesions greater than 10 mm did not differ significantly between groups. In a multivariate logistic regression analysis, only use of HD-CE was associated independently with increased polyp detection throughout the colon. CONCLUSIONS: In a randomized controlled trial, we found that panchromoendoscopy increases detection of polyps (mostly of small serrated lesions) and should be considered the standard of care in patients with SPS. Studies are needed to determine the effects of this strategy on the incidence of advanced neoplasia during long-term follow-up evaluation. ClinicalTrials.gov no: NCT03476434.