The urologist in the world of precision medicine

Raoul S. Concepcion, MD, FACS

Over the past few years, and particularly the past 12 months, we have witnessed the inclusion in the common parlance of prostate cancer the term precision medicine in the management of advanced disease. What exactly is precision medicine? When we launched LUGPA approximately 15 years ago, we struggled with defining the inherent advantages of defining what a large, vertically integrated, single-specialty group brought to health care and our patients. One of the original board members put it very simply: cheaper, faster, and better.

Often, we use the terms personalized medicine and precision medicine interchangeably. I believe all medicine is personalized. We make a diagnosis, consider pertinent details of the individual’s medical history that will influence our decision-making, and prescribe the appropriate therapy accordingly. It is not a one-size-fits-all approach. The National Cancer Institute formally defines precision medicine as "a form of medicine that uses information about a person’s own genes or proteins to prevent, diagnose, or treat disease. To break it down more simply: the correct therapy for the correct patient.

In general, we have managed all our genitourinary malignancies based on histopathologic criteria. Urothelial vs squamous vs adenocarcinoma of the bladder. Seminoma vs non-seminomatous germ cell of the testes. Obviously, for prostate cancer, it has been based on the redefined Gleason Score and Grade Group. For decades, we have recognized the hormonal influence and its effect on prostate cancer growth and progression. The past decade has led to a better understanding of the role of the androgen receptor (AR) and its mutagenicity to maintain function in advanced disease with subsequent development of newer, more novel molecules directed at the AR axis. However, all patients with progressive disease are started on baseline androgen deprivation therapy. We do not routinely measure for expression or activity. It is the foundation and fundamental to the management of disease that has been in practice for decades.

Contrast to our colleagues who manage breast cancer (another endocrine-driven cancer akin to prostate) where the histology is clearly important, but molecular expression of multiple receptor types will determine therapy. It is the standard of care before initiating treatment and how family members should be potentially screened and evaluated for risk. In fact, the presence of certain germline mutations (ie, BRCA1) may predict the risk of the molecular pattern (triple-negative receptor status). Over the past 8 years, we have tried to bridge this deficit and gain a better understanding of molecular drivers, especially as more agents are being used earlier in the disease spectrum and downstream mutations are the result. We must better educate ourselves on what they are, what insight can be gained, the timing of when to incorporate, and perhaps most importantly, what the limitations are.

Over the past few years, the menu has expanded and added more into our lexicon for prostate cancer: AR splice variants, proprietary somatic gene signatures, circulating tumor cells, cell-free DNA, DNA damage repair genes (encompassing both mismatch repair and homologous recombination), tumor mutation burden, prostate-specific membrane antigen, and beyond. For the most part, they all have value, and the question is how to best incorporate them into our practice to best manage our patients, whether it be newly diagnosed or those with progressive disease? To do so, we must take the time to understand how they all differ and what is actionable to prescribe appropriate next line of therapy—the correct therapy for the correct patient.

Reference

1. Dictionary of cancer terms. National Cancer Institute. Accessed February 22, 2022. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/precision-medicine