ESOU 2019: Why Genetic Tests are Not There Yet

Prague, Czech Republic ( Dr. Judd Moul presented a comprehensive overview of genetic tests in the setting of prevention, diagnosis and active surveillance.  Considering that genomics is a hot topic in cancer, Dr. Moul started by giving a brief overview of genetics, highlighting that somatic mutations are a change in the gene that arises in the tumor and is confined to the tumor, whereas germline mutations are a change in the gene that was inherited and therefore causes an increased risk for cancer.

In Dr. Moul’s opinion, there are several reasons why genetic tests are not there yet for prostate cancer. First, with regards to germline/hereditary considerations, there are legal and privacy concerns, limited therapeutics, issues with the accuracy and cost of current multi-gene tests and concerns about “which one is best”. Second, regarding somatic mutation testing, there is a lack of prospective randomized controlled trials, expense considerations, cost concerns, and a lack of clear guidelines. Tumor testing (ie tumor biopsy) can help guide treatment options (ie. Prolaris®, Oncotype DX®, Decipher®), whereas germline testing (ie. saliva or blood) can help determine if a mutation was inherited and help guide treatment and risk management options for patients and family members.

When Dr. Moul is considering an individual for hereditary screening he looks at three key items: multiple cancers (combination of cancers in a patient or the same side of the family), young patients (cancer at age 50 or younger in a patient or a family member), and rare tumors (in any age in a patient or a family member).

One of the more common genes with prostate cancer implications is the BRCA 1/2 family of mutations. Carriers of this mutation have a 20-fold increased risk than the general population for prostate cancer and a 7-fold increased risk of male breast cancer according to Dr. Moul. Furthermore, patients with BRCA 1/2 mutations that develop prostate cancer have a higher risk of nodal involvement, distant metastasis, and poor survival outcomes1. The now landmark paper by Prichard et al. 2 assessing DNA-repair gene mutations found that a total of 84 germline DNA-repair gene mutations presumed to be deleterious were identified in 82 men (11.8% of those tested), most commonly BRCA2 (5.3%) and ATM (1.6%).

Dr. Moul then highlighted the current status of genetic testing at his institution, Duke University:

  • Germline testing in nearly all men with metastatic prostate cancer
  • Specific hereditary tests include Invitae or Color, which many insurers now cover given recent NCCN guideline updates
  • If they find a positive test, the patient is referred to the hereditary cancer clinic
  • They have kits in the clinic to use and their nurses are trained to test patients in ~10 minutes
  • They have several tests approved for somatic testing in the localized prostate cancer setting, including Prolaris, Oncotype Dx, Decipher (post-radical prostatectomy), PHI, and ConfirmMDx®
Dr. Moul notes that there are several limitations of Prolaris and Oncotype Dx in that neither has been prospectively validated in an active surveillance population and it is unclear which of the two is better. He also notes that although the tests are costly ($3,000-$3,500 USD), Medicare does cover both tests. Furthermore, these tests are not globally available. Decipher is used on radical prostatectomy archival tissue in patients with adverse pathology to assist with offering adjuvant vs waiting for salvage therapy. Decipher high-risk patients who received adjuvant radiation have an 80% reduction in metastasis compared to those who waited for salvage therapy.

Dr. Moul concluded his presentation with several key take-home messages:
1. It is important to differentiate between germline and somatic genetic testing
2. For hereditary testing, this includes patients who may derive a survival benefit
3. For somatic testing, it remains to be seen whether these tests really make a long-term difference in outcomes. Among these tests, Decipher post-radical prostatectomy appears to have the strongest long-term benefit to date

Presented by: Judd Moul, MD, Urologic Oncologist, Duke University, Durham, North Carolina, USA

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md, at the 16th Meeting of the European Section of Oncological Urology, #ESOU19, January 18-20, 2019, Prague, Czech Republic

1. Castro E, Goh C, Olmos D, et al. Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. J Clin Oncol 2013 May 10;31(14):1748-1757.
2. Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-Repair gene mutations in men with metastatic prostate cancer. N Engl J Med. 2016;375(5):443-453.
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