|1R37CA276306-01A1 Interpret this number
|Kaiser Foundation Research Institute
|Personalizing Post-Polypectomy Surveillance for Colorectal Cancer Prevention
PROJECT SUMMARY AND ABSTRACT
Screening is an established method for decreasing colorectal cancer (CRC) incidence and mortality. However,
despite guidance supporting CRC screening initiation (i.e., 45 years), relatively little is known about what to do
after a precancerous polyp is detected and removed. This is particularly concerning given that over 40% of
individuals who undergo CRC screening are found to have a precancerous polyp and then instructed to
undergo frequent colonoscopies (termed surveillance) every 3-10 years for CRC risk reduction. Current
guidelines utilize a risk-stratification scheme that categorizes patients as high or low risk based only on polyp
characteristics from their initial colonoscopy. However, polyp-based risk stratification methods are imprecise,
with a sensitivity and specificity of 59-81% and 43-58%, respectively, for predicting subsequent advanced
neoplasia after polyp removal. Thus, our current guideline-based risk stratification methods both miss high-risk
individuals who may benefit from early surveillance and subject many low-risk individuals to unnecessary
colonoscopies and its associated harms. Recent studies from our group and others have identified several
clinical and genetic (i.e., polygenic risk score) risk factors associated with CRC; these may further optimize risk
stratification following CRC screening and polyp removal, but remain understudied. For this R01 proposal, we
will first develop and validate a practical, clinically useful risk prediction tool that incorporates both detailed
polyp characteristics and other important predictors known to play an important role in CRC risk, such as
clinical and genetic (i.e., polygenic risk score) risk factors (Aims 1 and 2). Second, we will identify optimal
strategies for CRC surveillance given individual risk estimates defined in Aims 1-2 and evaluate the cost-
effectiveness of different risk-stratified surveillance strategies compared to current guideline recommended
polyp-based surveillance strategies (Aim 3). This Aim will leverage our ongoing collaboration with an
established, internationally recognized micro-simulation model (MISCAN-Colon) that informs U.S. Preventative
Task Force recommendations. Lastly, we will gain patient, clinician, and service provider’s perspectives on
these novel comprehensive risk prediction methods, to optimize potential adoption, and assess potential
implementation barriers and facilitators (Aim 4). This aim will incorporate group experiences with mixed
methods techniques to identify attitudes and barriers of implementation. The overall aims will leverage
comprehensive data from an extremely large contemporary community-based cohort and an independent
cohort for validation. These cohorts’ detailed data include genome-wide genotype arrays coupled with prior
screening, pathologic and clinical data, and surveillance outcomes. This study can substantially transform how
we manage care for over 7 million patients diagnosed annually with precancerous polyps, personalize post-
polypectomy surveillance using a new, novel, comprehensive, patient-centered risk prediction model, and
optimize post-polypectomy surveillance to reduce CRC incidence and mortality.
Predicting Risk of Colorectal Cancer After Adenoma Removal in a Large, Community-based Setting.
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The American journal of gastroenterology, 2024-02-14; , .