Precision Oncology: Who, How, What, When, and When Not?

Abstract

Precision oncology, defined as molecular profiling of tumors to identify targetable alterations, is rapidly developing and has entered the mainstream of clinical practice. Genomic testing involves many stakeholders working in a coordinated fashion to deliver high-quality tissue samples to high-quality laboratories, where appropriate next-generation sequencing (NGS) molecular analysis leads to actionable results. Clinicians should be familiar with the types of genomic variants reported by the laboratory and the technology used to determine the results, including limitations of current testing methodologies and reports. Interpretation of genomic results is best undertaken with multidisciplinary input to reduce uncertainty in clinical recommendations relating to a documented variant. Non–small cell lung cancer has emerged as a prototype disease where genomic data from at least several well-documented alterations with approved targeted agents are essential for optimal treatment from diagnosis of advanced disease. Due to the development of resistance to targeted therapies, resampling and retesting of tumors, including using liquid biopsy technology after clinical progression, may be important in making treatment decisions. The value of molecular profiling depends on avoiding both underutilization for well-documented variant target-drug pairs and overutilization of variant-drug therapy without proven benefit. As techniques evolve and become more cost effective, the use of molecular testing may prove to add more specificity and improve outcomes for a larger number of patients.