Is It Time to Expand Our Definition of “Clinical Utility”?

Currently, genetic tests that predict cancer risk or risk of recurrence in patients who have had their cancer treated with curative intent must have proven “clinical utility” to be recommended by the organizations responsible for publishing the standard-of-care guidelines for cancer care. Based on the current definition of clinical utility, most patients are denied testing for cancer-predisposing genes or pathogenic germline variants even though germline testing has been proven as highly accurate in identifying pathogenic germline variant carriers, there are measures recommended to prevent and diagnose early cancers associated with particular PGVs, and disparities in patient access to genetic tests are well described. Similarly, despite dozens of studies demonstrating that detected circulating tumor DNA (ctDNA) after curative intention therapy of different cancer types is a highly accurate biomarker that predicts recurrence, the major organizations that publish guidelines for cancer monitoring after curative intention therapy recommend against using ctDNA assays to detect minimal residual disease and thereby predict recurrence for all solid tumor malignancies. Here, the primary reasons that these genetic tests are considered to lack proven clinical utility and the primary evidence suggesting that a broader definition of clinical utility should be considered are discussed. By expanding the definition of clinical utility, many patients will benefit from the information gained from having these genetic tests.