An Introduction To Genomic Testing For Prostate Cancer

(UroToday.com) In anticipation of the 2021 American Urological Association (AUA) Annual Meeting which is being held, in a delayed fashion, in September, the AUA hosted a “May Kick-Off Weekend” which highlighted a variety of important topics in both benign urology and urologic oncology. Sunday afternoon, Joseph Wagner led a course entitled “Incorporating Genomic Testing For Prostate Cancer into Your Practice” along with faculty Daniel Lin and Matthew Cooperberg.

Dr. Wagner began with an introduction to genomic testing, emphasizing the difference between somatic mutations (affecting any cell of the body apart from germ cells, but most typically tumor cells in this context) and germline mutations (affecting all cells in the body, including germ cells, which may be transferred to offspring). As expected from the name, germline tests examine mutations that are inherited and may be detected in any cell. Thus, these tests typically are performed on blood, saliva, buccal swab or other non-tumor sources. In contrast, genomic tests look for somatic mutations within the tumor. Notably, some tests which are grouped within this category do not detect mutations, but rather examine other changes including DNA methylation and protein expression.

As highlighted in the following figure, there is a rapidly growing role for genomic testing across the entire landscape of prostate cancer from the initial decision to screen through to treatment decisions in advanced disease.

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Dr. Wagner then briefly reviewed the central dogma of molecular biology, describing the follow of genetic information from DNA, through messenger RNA, to protein. Genetic and genomic tests may assess any step along this pathway, including the IMPACT testing for DNA-level changes, OncotypeDx which examines RNA signatures, and ProMark which examines protein expression.

Dr. Wagner then provided the rationale for genomic testing, highlighting that there is significant upgrading/upstaging and downgrading/downstaging following prostate biopsy suggesting that there is considerable room to improve out risk stratification to guide treatment decisions.

According to recent NCCN guidelines, as highlighted below, genomic testing is indicated and should be considered for a large proportion of patients with clinically localized disease.

Dr. Wagner then discussed considerations for choosing which test to use. In the talks as part of this course, the presenters focus on Prolaris, Decipher, Oncotype, and ProMark as these are specified in the NCCN guideline. However, choosing among these depends in part on understanding how each was derived: there is no single best test. Different tests, however, were designed to assess different endpoints and deciding which endpoint is most important in a given situation may help with selecting the most appropriate test.

Presented by: Joseph Robert Wagner, MD, Chief, Urology, Hartford Hospital & Director, Robotic Surgery, Hartford Hospital