Learning Objective

At the conclusion of the activity, participants will be able to describe which molecular tests can be performed on prostatectomy specimens and differentiate between somatic and germline mutations.

Mounting evidence suggests genomic tests are useful through all stages of prostate cancer diagnosis and treatment. “Incorporating Genomic Testing for Prostate Cancer into Your Practice” was selected as an Instructional Course for AUA2022 held in New Orleans. Led by course director Joseph Wagner, MD and a superb faculty comprised of Matthew Cooperberg, MD and Daniel Lin, MD, this course utilized an index case and a flipped classroom format to encourage participant engagement. The course focused on identifying a patient’s unique clinical characteristics, assessing prognostic endpoints, and reviewing American Urological Association and National Comprehensive Cancer Network® guidelines for genomic testing for prostate cancer.

A brief review demonstrates the pathway of DNA to RNA to proteins. Examples of tests examining each of these in the prostate cancer arena are given. The definition of germline and somatic mutations is explained (somatic mutations occur in a single body cell and cannot be inherited; germline mutations occur in gametes and can be passed into offspring). Studies demonstrating the high rates of upgrading/downgrading and upstaging/downstaging, and thereby the need for better prognostic tests, are discussed.

The index patient presents to his urologist with an elevated PSA. Stressing a shared decision-making process, prostate biopsy, MRI, surveillance, and molecular/genomic testing (4K, PHI, Select MDx, ExoDX™, etc) are all presented and a plan implemented. This process can be repeated for a negative biopsy with the addition of other tissue-based genomic tests performed on the biopsy material (Confirm MDx, etc). Our index patient is diagnosed with prostate cancer and chooses to utilize genomic testing to help him make a treatment decision and settles on surgery. Though he has a family history of prostate cancer, he does not meet the criteria for germline testing.¹ Unfortunately, his pathology specimen shows several adverse features. After discussing the 2 commercially available genomic tests that can be performed on prostatectomy specimens (Prolaris® and Decipher), he has genomic testing performed on the pathological specimen and is found to have a high risk of recurrence for which adjuvant or early salvage radiation has been shown to be advantageous over standard salvage radiation therapy.²

According to Joseph R. Wagner, MD, director of robotic surgery at Hartford Healthcare and chairman of the Department of Urology at Hartford Hospital in Connecticut, multiple genomic tests for men considering a prostate biopsy and at all stages of prostate cancer can aid in making different treatment decisions. Germline testing results can also influence a patient’s treatment options. For instance, a patient with a BRCA2 mutation is at higher risk for progression and may have a lower threshold for definitive therapy than a patient without a similar mutation. Furthermore, the family members of such a patient, both male and female, can consider testing.

“Genomic testing can dramatically influence the treatment of prostate cancer. A patient might migrate away from a prostate biopsy to continued monitoring of his PSA and be spared the diagnosis of a clinically insignificant prostate cancer. He may choose active surveillance over definitive therapy based on the result of genomic testing,” Dr. Wagner said. “His genomic test may aid his radiation oncologist concerning the need for concurrent androgen deprivation therapy with his radiation. Genomic testing can help a patient decide whether to pursue adjuvant or early salvage treatment. Clearly, the influence of genomic testing is significant.”

The availability and marketing of genomic testing has outpaced a deliberate, evidence-based medicine approach to using these tests. Multiple seminal validation studies used in the approval of genomic tests are presented and underscore their importance in prostate cancer detection and treatment decision making. The utilization of PARP inhibitors to treat castrate resistant metastatic prostate cancer in men with germline BRCA2 mutations is an excellent example of the rapidly evolving field of precision medicine based on genomic testing results. Although not all patients require such tests, they can be useful depending on the clinical circumstances, according to Dr. Wagner.

In determining which patients to test, the first step for doctors should be to familiarize themselves with National Comprehensive Cancer Network/American Urological Association guidelines and the genomic tests that are available, according to Dr. Wagner. All the tests have different clinical endpoints and utilities; therefore, it is important to understand the characteristics of each to determine which patients are appropriate for genomic testing. It is with this kind of understanding that the doctor and patient can participate in shared decision making.³

“Personally, I prefer to explain the nuances of the various tests and help the patient decide which is best for him. For instance, if a patient is deciding between active surveillance and definitive treatment, the clinical outcome of one test compared to another might be more appealing to him as he makes a challenging decision,” Dr. Wagner said.

DNA, RNA, and proteins are responsible for the current parameters (PSA, Grade Group, etc) used to determine the clinical significance of prostate cancer. It stands to reason that adding genomic tests which directly examine DNA/RNA/proteins will enhance the prognostic utility of these traditional parameters. Continued medical education is crucial to help urologists stay current in this rapidly changing field.

Acknowledgment

We thank Tara McLaughlin, PhD for her help with reviewing the article.