The Impact of Location of Colon Polyps at Colonoscopy on Risk of Colorectal Cancer Incidence and Mortality: Secondary Analyses of the PLCO Trial
remains largely unknown. Published data suggest higher rates of metachronous neoplasia for adenomas that are advanced, defined as polyps having high risk features (size >1 cm, any villous histology or high-grade dysplasia), and malignant polyps (superficial submucosal invasion; pT1 CRC), together called advanced neoplasia but the role of polyp location on risk of CRC has not been well studied. Given limited evidence, the US Multi-Society Task Force on CRC guidelines called for more research to determine whether proximal location should be considered as a specific factor for modifying surveillance protocols. The overall hypothesis of this research is that proximal adenomas and advanced adenomas, have a higher incidence of post-colonoscopy adenocarcinoma, hence worse prognosis, and should therefore be treated and surveilled with more aggressive protocols. To begin to address this hypothesis we have explored two national databases, and demonstrated worse outcomes for patients with proximal advanced neoplasia (AN). We have
subsequently confirmed these findings, expanding the results to any colonic adenoma, in a secondary analysis of the Minnesota Colon Cancer Cohort Study (MCCCS); this was first trial to show a positive impact of CRC screening on disease-specific mortality. We seek to analyze data from the Prostate, Lung, Colon, Ovary Screening Trial (PLCO), a long-term clinical trial on the effect of CRC screening on CRC incidence and mortality, to further validate our results, providing robust data to modify surveillance guidelines for colonic lesions excised endoscopically, based on tumor location. The PLCO collected several epidemiologic data for >60,000 patients screened for CRC between 1993 and 2001 with median follow-up extending to 20 years. We believe the results of these analyses can significantly impact clinical guidelines.
Aim 1: To study the overall and CRC-specific mortality of patients with proximal versus distal colonic lesions (adenoma, advanced adenoma, and malignant polyp) following endoscopic resection. We wil identify all adult patients who underwent an endoscopic polypectomy during the PLCO study, and analyze the
survival outcomes based on colonic lesion location, after adjusting for confounders. Colonic polyps will be classified as proximal if located proximal to the splenic flexure, and distal if at or distal to the splenic flexure. Colonic polyps will be grouped as adenomas, advanced adenomas, and malignant polyps. Cox regression models will be utilized to assess for survival differences by laterality.
Hypothesis 1: Patients with proximal lesions have worse outcomes than those with distal lesions post colonoscopy.
Aim 2: To study the cumulative CRC-incidence and site of CRC for proximal versus distal colonic lesions. We will study the cumulative incidence, and location of subsequently developed CRC (in 1-10 years after index colonoscopy) for those who were found with any colonic lesion at their index endoscopic
examination in either proximal or distal colon, compared to those with no polyps at index colonoscopy. Competing risk models will be used to assess the effect of location on cumulative incidence of CRC while adjusting for the potential confounding effects of histologic characteristics.
Hypothesis 2: Proximal lesions have higher rates and shorter time-interval of developing CRC post colonoscopy.
Aim 3: To develop a comprehensive prediction model for post colonoscopy CRC and CRC-specific mortality based on colonic lesion location, histology and patient and colonoscopy factors. Current surveillance intervals are determined by size, number, and histology of colon lesions at index colonoscopy.
We will add location of colonic lesion, patient and colonoscopy factors and create a comprehensive risk score for assessing surveillance interval. The resulting risk tool built in a research environment will provide a practical tool enhancing clinical implementation of the results which can eventually be translated into practice.
Hypothesis 3: Addition of location of colonic lesions would improve the prediction of post colonoscopy CRC incidence and mortality.
Aasma Shaukat, MD, MPH
Tim Church, PhD