When Actionable Genomic Findings Do Not Translate into Treatment in Precision Oncology.

Comprehensive genomic profiling has expanded the ability to identify potentially actionable molecular alterations across cancers, but identification of an actionable finding does not ensure that a patient will receive a genomically matched therapy. Studies of precision-oncology programs and molecular tumor boards consistently demonstrate substantial attrition between treatment recommendation and treatment initiation. The reasons extend beyond molecular interpretation and include the timing of genomic profiling, clinical deterioration, geographic availability of biomarker-selected trials, insurance and financial barriers, and disparities in access to specialty cancer care. Importantly, these barriers arise after a potentially useful molecular finding has already been identified, creating a distinction between molecular actionability and practical treatment access. This commentary argues that the next implementation challenge for precision oncology is to make clinically meaningful genomic findings realistically actionable. Comprehensive genomic profiling should occur early enough to inform treatment planning; molecular tumor board recommendations should be linked to realistic treatment and trial opportunities; financial and insurance barriers should be anticipated when recommendations are made; and equity should be evaluated beyond access to testing to include receipt of genomically informed treatment. As genomic profiling becomes increasingly integrated into routine cancer care, precision oncology should be judged not only by its ability to identify therapeutic opportunities but also by whether patients can reach those opportunities while they remain clinically relevant.