<i>CLINICAL FEATURES, PROGNOSIS, AND RISK FACTORS OF POST-COLONOSCOPY </i><i>COLORECTAL CANCER IN A LARGE INTEGRATED HEALTHCARE SYSTEM</i>

Background & Aims
Colonoscopy surveillance intervals are based on the predicted risk of metachronous colorectal cancer (CRC) after polyp removal. Due to the presence of co-existent findings at baseline colonoscopy, risk estimation per specific polyp subtype is difficult. To investigate the metachronous CRC risk, we evaluated the risk of patient groups with and without co-occuring findings.
Methods
Using screening colonoscopies performed after a positive fecal immunochemical test between 2014-2020 within the Dutch CRC screening program, we applied Cox regression analysis to evaluate the association between findings at baseline colonoscopy and metachronous CRC. Metachronous cancer cases, defined as CRCs diagnosed after 6 months of baseline colonoscopy, were collected from the Dutch Cancer Registry. Risk of subgroups based on polyp findings were compared to individuals without polyps in two different models. In model 1, individuals were classified into eight different subgroups based on the presence or absence of advanced adenomas and/or advanced serrated polyps. In model 2, we included presence of individual polyp characteristics in a multivariable analysis. Both models were adjusted for individuals’ sex and age. A hazard ratio >1.5 was considered clinically relevant. Advanced serrated polyps (ASP) were defined as serrated polyp ≥10mm, sessile serrated lesion with dysplasia, or traditional serrated adenoma.
Results
253,833 colonoscopies were included. Over a median follow-up of 36 months (IQR, 21-57), we identified 504 metachronous CRC cases. HR for CRC was 1.70 (CI95%, 1.07-2.69) for individuals with ASP without advanced adenomas (AA), 1.22 (0.96-1.55) for individuals with AAs without ASPs, and 2.00 (1.19-3.39) for individuals with ASPs and AA, compared to patients without polyps (Table 1). Individuals with non-advanced adenomas and/or non-advanced serrated polyps did not have an increased CRC risk. Model 2 showed that any villous adenoma (HR 2.732, 1.725-4.329), serrated polyp ≥10mm (HR 1.61; 1.06-2.45), sessile serrated lesion with dysplasia (HR 2.09; 1.12-3.88), traditional serrated adenoma (HR 2.668, 1.434-4.965), adenoma with high-grade dysplasia (HR 3.59; 2.17-5.94) and presence of at least five non-advanced adenomas (HR 2.13; 1.10-4.10) resulted in a clinically relevant increased risk for CRC, while any adenoma ≥10mm did not (HR 0.96; 0.74-1.25) (Table 2).
Conclusion
By evaluating high-quality screening colonoscopies with a median follow-up of 3 years and accounting for co-occuring findings, we observed an increased CRC risk in individuals that had ASPs with the presence of AAs, or individuals with ASPs without AAs. These findings could contribute to establish more restrictive post-polypectomy surveillance guidelines.

Background: Post-colonoscopy colorectal cancer (PCCRC) is defined as cancers diagnosed after a colonoscopy in which no cancer is found. The clinical features, prognosis, and risk factors of PCCRC remain poorly characterized.
Methods: In a large healthcare system (Mass General Brigham), we assembled a longitudinal cohort of patients who had undergone a colonoscopy between 2010-2018 by extracting detailed endoscopic, pathologic, and other clinical data from the electronic health records. We identified patients who were diagnosed with CRC between 6 and 48 months after a CRC-free index colonoscopy (PCCRC<4y) and at least 48 months after a CRC-free colonoscopy (PCCRC≥4y). We conducted chart review to categorize the causes of PCCRC according to the World Endoscopy Organization (WEO) recommendations and compared the anatomic subsites, stages, and survival between PCCRC<4y and PCCRC≥4y. We then matched up to 3 controls for each CRC patient based upon age, sex, race/ethnicity, and time and reason of index colonoscopy; and assessed potential risk factors for PCCRC using conditional logistic regression and accounting for missing data via multiple imputation.
Results: During a median follow-up of 5.6 years among 198,066 patients with a CRC-free index colonoscopy, we documented 121 incident PCCRC<4y and 86 PCCRC≥4y cases (females: 42% vs. 53%; mean age=67.7 vs. 70.1 years; median interval between index colonoscopy and diagnosis=2.2 vs. 6.0 years). According to the WEO categorization, 90% of PCCRC<4y cases likely occurred due to possible missed lesions or inadequate exam. Compared to PCCRC≥4ys, PCCRC<4ys had a more advanced stage at diagnosis (p=0.004) but no statistically significant difference in subsites (p=0.56). Among patients with a polyp finding in the index colonoscopy, PCCRC<4ys were more likely to arise in the same broad location (proximal colon, distal colon, and rectum) as prior polyps than PCCRC≥4ys, particularly in the proximal colon (57% vs. 18%). During a median follow-up of 4.6 and 3.3 years of PCCRC<4y and PCCRC≥4y patients, we documented 28 and 9 deaths, respectively; a lower 5-year survival was observed for PCCRC<4y than PCCRC≥4y (68% vs. 76%). By comparing PCCRC<4ys and PCCRC≥4ys and their matched controls (353 and 252 controls, respectively), we found that the presence of large (≥1 cm) index polyps was more strongly associated with higher risk of PCCRC<4ys than PCCRC≥4ys (p for heterogeneity=0.006), whereas no significant difference was found in other risk factors, including histology and multiplicity of index polyps and family history of CRC.
Conclusions: 90% of PCCRC<4y cases are avoidable via improved colonoscopy quality and lesion detection. PCCRC<4y had more unfavorable clinical profiles than PCCRC≥4y. Patients with large index polyps were at a particularly high risk of developing PCCRC<4y, likely in the same location.