Low Colorectal Cancer Risk After Resection of High-Risk Pedunculated Polyps.

BACKGROUND: Post-fecal immunochemical test (FIT) colonoscopy represents a setting with an enriched prevalence of advanced adenomas. Due to an expected higher risk of colorectal cancer (CRC), postpolypectomy surveillance is recommended, generating a substantially increased load on endoscopy services. The aim of our study was to investigate postpolypectomy CRC risk in a screening population of FIT+ subjects after resection of low-risk adenomas (LRAs) or high-risk adenomas (HRAs). METHODS: We retrieved data from a cohort of patients undergoing postpolypectomy surveillance within a FIT-based CRC screening program in Italy between 2002 and 2017 and followed-up to December 2021. Main outcomes were postpolypectomy CRC incidence and mortality risks according to type of adenoma (LRA/HRA) removed at colonoscopy as well as morphology, size, dysplasia, and location of the index lesion. We adopted as comparators FIT+/colonoscopy-negative and FIT- patients. The absolute risk was calculated as the number of incident CRCs per 100,000 person-years of follow-up. We used Cox multivariable regression models to identify associations between CRC risks and patient- and polyp-related variables. RESULTS: Overall, we included 87,248 post-FIT+ colonoscopies (133 endoscopists). Of these, 42,899 (49.2%) were negative, 21,650 (24.8%) had an LRA, and 22,709 (26.0%) an HRA. After a median follow-up of 7.25 years, a total of 635 CRCs were observed. For patients with LRAs, CRC incidence (hazard ratio [HR], 1.18; 95% confidence interval [CI], 0.92-1.53) was not increased compared with the FIT+/colonoscopy-negative group, while for HRAs a significant increase in CRC incidence (HR, 1.53; 95% CI, 1.14-2.04) was found. The presence of 1 or more risk factors among proximal location, nonpedunculated morphology, and high-grade dysplasia explained most of this excess CRC risk in the HRA group (HR, 1.85; 95% CI, 1.36-2.52). Patients with only distal pedunculated polyps without high-grade dysplasia, representing 39.2% of HRA, did not have increased risk compared with the FIT- group (HR, 0.87; 95% CI, 0.59-1.28). CONCLUSIONS: CRC incidence is significantly higher in patients with HRAs diagnosed at colonoscopy. However, such excess risk does not appear to apply to patients with only distal pedunculated polyps without high-grade dysplasia, an observation that could potentially reduce the burden of surveillance in FIT programs.

Adenoma Detection Rate and Colorectal Cancer Risk in Fecal Immunochemical Test Screening Programs : An Observational Cohort Study.

BACKGROUND: Colorectal cancer (CRC) screening programs based on fecal immunochemical tests (FITs) represent the standard of care for population-based interventions. Their benefit depends on the identification of neoplasia at colonoscopy after FIT positivity. Colonoscopy quality measured by adenoma detection rate (ADR) may affect screening program effectiveness. OBJECTIVE: To examine the association between ADR and postcolonoscopy CRC (PCCRC) risk in a FIT-based screening program. DESIGN: Retrospective population-based cohort study. SETTING: Fecal immunochemical test-based CRC screening program between 2003 and 2021 in northeastern Italy. PATIENTS: All patients with a positive FIT result who had a colonoscopy were included. MEASUREMENTS: The regional cancer registry supplied information on any PCCRC diagnosed between 6 months and 10 years after colonoscopy. Endoscopists' ADR was categorized into 5 groups (20% to 39.9%, 40% to 44.9%, 45% to 49.9%, 50% to 54.9%, and 55% to 70%). To examine the association of ADR with PCCRC incidence risk, Cox regression models were fitted to estimate hazard ratios (HRs) and 95% CIs. RESULTS: Of the 110 109 initial colonoscopies, 49 626 colonoscopies done by 113 endoscopists between 2012 and 2017 were included. After 328 778 person-years follow-up, 277 cases of PCCRC were diagnosed. Mean ADR was 48.3% (range, 23% and 70%). Incidence rates of PCCRC from lowest to highest ADR group were 13.13, 10.61, 7.60, 6.01, and 5.78 per 10 000 person-years. There was a significant inverse association between ADR and PCCRC incidence risk, with a 2.35-fold risk increase (95% CI, 1.63 to 3.38) in the lowest group compared with the highest. The adjusted HR for PCCRC associated with 1% increase in ADR was 0.96 (CI, 0.95 to 0.98). LIMITATION: Adenoma detection rate is partly determined by FIT positivity cutoff; exact values may vary in different settings. CONCLUSION: In a FIT-based screening program, ADR is inversely associated with PCCRC incidence risk, mandating appropriate colonoscopy quality monitoring in this setting. Increasing endoscopists' ADR may significantly reduce PCCRC risk. PRIMARY FUNDING SOURCE: None.

Adenoma detection by Endocuff-assisted versus standard colonoscopy in an organized screening program: the "ItaVision" randomized controlled trial.

BACKGROUND: The Endocuff Vision device (Arc Medical Design Ltd., Leeds, UK) has been shown to increase mucosal exposure, and consequently adenoma detection rate (ADR), during colonoscopy. This nationwide multicenter study assessed possible benefits and harms of using Endocuff Vision in a fecal immunochemical test (FIT)-based screening program. METHODS: Patients undergoing colonoscopy after a FIT-positive test were randomized 1:1 to undergo Endocuff-assisted colonoscopy or standard colonoscopy, stratified by sex, age, and screening history. Primary outcome was ADR. Secondary outcomes were ADR stratified by endoscopists' ADR, advanced ADR (AADR), adenomas per colonoscopy (APC), withdrawal time, and adverse events. RESULTS: 1866 patients were enrolled across 13 centers. After exclusions, 1813 (mean age 60.1 years; male 53.8 %) were randomized (908 Endocuff Vision, 905 standard colonoscopy). ADR was significantly higher in the Endocuff Vision arm (47.8 % vs. 40.8 %; relative risk [RR] 1.17, 95 % confidence interval [CI] 1.06-1.30), with no differences between arms regarding size or morphology. When stratifying for endoscopists' ADR, only low detectors (ADR < 33.3 %) showed a statistically significant ADR increase (Endocuff Vision 41.1 % [95 %CI 35.7-46.7] vs. standard colonoscopy 26.0 % [95 %CI 21.3-31.4]). AADR (24.8 % vs. 20.5 %, RR 1.21, 95 %CI 1.02-1.43) and APC (0.94 vs. 0.77; P  = 0.001) were higher in the Endocuff Vision arm. Withdrawal time and adverse events were similar between arms. CONCLUSION: Endocuff Vision increased ADR in a FIT-based screening program by improving examination of the whole colonic mucosa. Utility was highest among endoscopists with a low ADR.

Comparing CT colonography and flexible sigmoidoscopy: a randomised trial within a population-based screening programme.

IMPORTANCE AND AIMS: The role of CT colonography (CTC) as a colorectal cancer (CRC) screening test is uncertain. The aim of our trial was to compare participation and detection rate (DR) with sigmoidoscopy (flexible sigmoidoscopy (FS)) and CTC in a screening setting. DESIGN SETTING AND PARTICIPANTS: We conducted two randomised clinical trials (RCTs). (1) Participation RCT: individuals, aged 58 years, living in Turin (Italy), were randomly assigned to be invited to FS or CTC screening; (2) detection RCT: residents in northern Italy, aged 58-60, giving their consent to recruitment, were randomly allocated to CTC or FS. Polyps ≥6 mm at CTC, or 'high-risk' distal lesions at FS, were referred for colonoscopy (TC). MAIN OUTCOME MEASURES: Participation rate (proportion of invitees examined); DR of advanced adenomas or CRC (advanced neoplasia (AN)). RESULTS: Participation was 30.4% (298/980) for CTC and 27.4% (267/976) for FS (relative risk (RR) 1.1; 95% CI 0.98 to 1.29). Among men, participation was higher with CTC than with FS (34.1% vs 26.5%, p=0.011). In the detection RCT, 2673 subjects had FS and 2595 had CTC: the AN DR was 4.8% (127/2673, including 9 CRCs) with FS and 5.1% (133/2595, including 10 CRCs) with CTC (RR 1.08; 95% CI 0.85 to 1.37). Distal AN DR was 3.9% (109/2673) with FS and 2.9% (76/2595) with CTC (RR 0.72; 95% CI 0.54 to 0.96); proximal AN DR was 1.2% (34/2595) for FS vs 2.7% (69/2595) for CTC (RR 2.06; 95% CI 1.37 to 3.10). CONCLUSIONS AND RELEVANCE: Participation and DR for FS and CTC were comparable. AN DR was twice as high in the proximal colon and lower in the distal colon with CTC than with FS. Men were more likely to participate in CTC screening. TRIAL REGISTRATION NUMBER: NCT01739608; Pre-results.

Comparison between different colon cleansing products for screening colonoscopy. A noninferiority trial in population-based screening programs in Italy.

BACKGROUND AND STUDY AIMS: The high volume and poor palatability of 4 L of polyethylene glycol (PEG)-based bowel cleansing preparation required before a colonoscopy represent a major obstacle for patients. The aim of this study was to compare two low volume PEG-based preparations with standard 4 L PEG in individuals with a positive fecal immunochemical test (FIT) within organized screening programs in Italy. PATIENTS AND METHODS: A total of 3660 patients with a positive FIT result were randomized to receive, in a split-dose regimen, 4 L PEG or 2 L PEG plus ascorbate (PEG-A) or 2 L PEG with citrate and simethicone plus bisacodyl (PEG-CS). The noninferiority of the low volume preparations vs. 4 L PEG was tested through the difference in proportions of adequate cleansing. RESULTS: A total of 2802 patients were included in the study. Adequate bowel cleansing was achieved in 868 of 926 cases (93.7 %) in the 4 L PEG group, in 872 out of 911 cases in the PEG-A group (95.7 %, difference in proportions  + 1.9 %, 95 % confidence interval [CI]  - 0.1 to 3.9), and in 862 out of 921 cases in the PEG-CS group (93.6 %, difference in proportions  - 0.2 %, 95 %CI  - 2.4 to 2.0). Bowel cleansing was adequate in 95.5 % of cases when the preparation-to-colonoscopy interval was between 120 and 239 minutes, whereas it dropped to 83.3 % with longer intervals. Better cleansing was observed in patients with regular bowel movements (95.6 %) compared with those with diarrhea (92.4 %) or constipation (90.8 %). CONCLUSION: Low volume PEG-based preparations administered in a split-dose regimen guarantee noninferior bowel cleansing compared with 4 L PEG. Constipated patients require a personalized preparation. TRIAL REGISTRATION: EudraCT 2012 - 003958 - 82.