Published online Feb 28, 2018. doi: 10.3748/wjg.v24.i8.905
Peer-review started: August 5, 2017
First decision: August 30, 2017
Revised: November 17, 2017
Accepted: December 5, 2017
Article in press: December 5, 2017
Published online: February 28, 2018
Screening colonoscopy has a 3.5% false negative rate for detection of colorectal cancer (CRC) resulting in 17% of patients who had undergone colon screening within 3 years being diagnosed with CRC. However, no large studies have assessed the frequency and risk factors for CRC development among individuals following advanced adenoma (AA)/traditional serrated adenoma (TSA)/advanced sessile serrated adenoma (ASSA) removal. Recognition of this group at high-risk for interval CRC is one step toward preventing morbidity and mortality associated with CRC development.
Recognition that CRC could develop following AA/TSA/ASSA removal despite adherence to guidelines is one step toward improving our practice efficiency and preventing a portion of CRC related morbidity and mortality. Understanding risk factors and developing molecular markers that predict progression may become important in order to individualize surveillance recommendations and recognize those AA/TSA/ASSA patients at high-risk for interval CRC.
To report the frequency of interval CRC development following high-risk polypectomy at the polypectomy site and another site distinct from polypectomy site and to identify risk factors associated with development of cancer. Realizing these objective is critical for future research since current evidence-based surveillance guidelines are limited in predicting CRC risk in these patients.
We reviewed medical records of all adult patients ( ≥ 18 years of age) who underwent colonoscopy (between January 1990 to December 2010 ) and were found to have high-risk polyps ( either AA between January 1990 to December 2010 or ASSA/TSA between January 2000 to December 2010 ) to identify 4160 patients who had at least one follow-up surveillance colonoscopy following polypectomy. We excluded patients with IBD, polyposis syndromes or other genetic syndromes predisposing for CRC. Patients with a past history of CRC were not excluded from our study. From this cohort, we identified 84 patients who had developed CRC and matched to 252 patients who had not developed CRC based on polyp histology and size (< or ≥ 20 mm), degree of dysplasia and decade that the index polyp was removed. Data abstracted included clinical and pathological features of high-risk polyps, number and timing of surveillance colonoscopies and post polypectomy CRC.
The data are reported as mean (± SD), median (interquartile range, IQR), ranges, and categorical variables by counts and percentages as appropriate. Estimates of the rate of cancer for the entire cohort were determined by using the Kaplan-Meier survival curve with log-rank test. We performed univariate time-to-event analysis with Cox proportional regression models to identify risk factors associated with development of cancer. Variables with P < 0.05 on univariate analysis were included in a multivariate Cox proportional hazard analysis to identify independent risk factors associated with malignancy. Finally, penalized regression models were run using Lasso regression, with 10-fold cross validation, to provide robust estimates of the model coefficients, which should provide better predictions when used with external data. All statistical analyses were conducted using JMP version 10 for Windows (SAS Institute Inc., Cary, NC, United States), SAS (version 9) or R (version 3.2.3).
Despite colonoscopic surveillance and management of high-risk polyps, 1.8% of patients developed post polypectomy CRC at or the index polyp site and 1.2% developed CRC at a site distinct from the index AA/TSA/ASSA. About one-third of patients developed CRC at the polypectomy site despite following appropriate surveillance intervals. Increasing age at the time of polypectomy, number of polyps, polyp size, location, degree of dysplasia, and piecemeal resection were associated with increased CRC risk. Current surveillance guidelines are not sufficient since it does not take into account the impact of multiple high-risk features of high-risk polyps for CRC development. This study also highlights the risk of missing additional adenomas or cancers at a surveillance colonoscopy for follow up of an index AA/TSA/ASSA. Resection technique (Piecemeal snare excision) was an independent risk factor for post polypectomy CRC in this study; but further prospective studies are needed to examine the prognostic utility of EMR with CRC development.
1.8% of patients developed post polypectomy CRC at the index polyp site and 1.2% developed CRC at a site distinct from the index AA/TSA/ASSA despite surveillance colonoscopy. Surveillance colonoscopy for high-risk polyp does not always prevent CRC cancer development. Current surveillance guidelines are not sufficient in predicting CRC risk in some patients. Incorporate the impact of multiple high-risk features of resected polyps in surveillance guidelines. Interval CRC develops after high-risk polyp resection despite being in a surveillance program. We compared patients who had developed interval CRC after high-risk polyp resection at same site and different site and matched to patients who had not developed CRC to identify risk factors associated with CRC development. Patients with increasing age and a history of large, multiple, highly dysplastic, right-sided, and difficult to remove adenomas requiring piecemeal resection are a high-risk population for the development of CRC at the same site. Increasing age and the presence of flat and/or right-sided adenomas increased the risk of CRC at another site. Colonoscopy is not 100% sensitive tool in the identification or prevention of CRC. Shortened surveillance intervals may be needed post-polypectomy in some patients with multiple high-risk features.
Interval CRC cancer rate after high-risk polyp resection is low yet CRC does develop in spite of post-polypectomy surveillance. We require further research to identify molecular or other features to guide more individualized polyp management. Study molecular features of patients who developed CRC at the polypectomy site despite following appropriate surveillance intervals