Systematic Evidence Reviews on the Clinical Utility of Cancer-Site Specific Polygenic Risk Scores (PRS) for Cancer Risk Assessment

Overview

Administrative supplements to conduct systematic evidence reviews on the clinical utility of cancer-site specific polygenic risk scores (PRS) for cancer risk assessment.

The development of PRS for cancer risk assessment has the potential to clarify risk assessment and improve preventive care and risk management. Here we are referring to PRS as mathematical models that use germline genetic information to estimate cancer risk. Prior to the development of PRS, risk models were based on family history and other known risk factors. Studies have been conducted to assess the validity of PRS as estimates of risk, comparing PRS to other models of risk, and examining the validity of models combining PRS with other risk factors. Models have been developed for a variety of different types of cancers, including breast, prostate, ovarian, lung, colorectal, and melanoma. The development, evaluation, and implementation of PRS alone or combined with other risk models for cancer risk assessment are complex, and it is critical that these models are thoroughly evaluated prior to implementation to ensure that they can be effectively used in clinical practice to improve patient outcomes.

While PRS have the potential to improve cancer risk assessment and preventive care, additional research is needed to understand issues related to evaluation and establishment of clinical utility (CU) prior to clinical implementation. The determination of CU involves the identification of the clinical benefits and harms of the use of PRS in terms of patient outcomes, ideally evaluated in randomized controlled trials. Before clinical use, the validity of the scores must be established. Factors to consider for validity include sensitivity, specificity, and discriminatory value to identify those at risk. Clinical utility considers whether the use of PRS guides appropriate clinical management and the benefits and harms of clinical use. Implementation of PRS, once CU is established, may consider additional factors such as positive and negative predictive value. A clear understanding of the CU of PRS will allow for the development of guideline-driven care that is linked to a specific threshold of risk and appropriate intervention.