Using clinicopathological data to determine risk of metachronous advanced colorectal neoplasia among patients with adenomas
The overall objective is to identify patients with an adenoma at highest risk for metachronous high-risk adenoma (HRA) or ACN within 3 or 5 years. We will use a retrospective observational study among participants aged 18+ who were randomized to receive the flexible sigmoidoscopy screening intervention in the PLCO trial and had an adenoma at baseline. The primary outcome will be HRA (>2 adenomas of any histology) or ACN (tubular adenoma ≥10 mm, adenoma with villous features or high grade dysplasia of any size, or invasive CRC) within 3 or 5 years of the first adenoma depending on year of randomization. The secondary outcome will be CRC diagnosis within 10 years. Covariates will include demographic, BMI, comorbidity, familial history, and lifestyle/diet predictors from baseline questionnaires, as well as colorectal adenoma location, size, number, and histology from the PLCO colorectal screening study. We plan to explore the following aims:
Aim 1: To develop, internally validate, and select the highest performing parametric or machine learning models to predict risk of HRA/ACN within 3 or 5 years among train and test cohorts of patients with an adenoma at the index flexible sigmoidoscopy.
Aim 2: To assess variable importance in the best performing model from Aim 1 to develop and assess the performance of a simplified model that can be applied in patients with an adenoma at screening.
Aim 3: To use probability from the simplified model in Aim 2 to stratify patients into low, medium, and high risk groups of HRA/ACN in 3 or 5 years and to assess model reclassification versus existing models.
External validation of the simplified model will be conducted.
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Laura Hester, Janssen R&D, LLC
Justin Callaway, Janssen R&D, LLC
Hari Singhal, Janssen R&D, LLC
Janeta Nikolovski, Janssen R&D, LLC
Gary Borzillo, Janssen R&D, LLC