Getting the Word Out 

Dr Cheng said a key goal is identifying patients with advanced disease and known mutations who may benefit from clinical trial opportunities as well as available treatments such as platinum chemotherapy.

“People are also thinking about earlier stages of the disease and, potentially, how to find those who may be at increased risk before they’re diagnosed or when the disease is potentially curable,” she said. The ability to sequence patients for germline mutations has also become much less expensive, and the ability to do more broad-based panel testing has increased, all of which she hopes will mean more patients will get screened.

In general, both the Consortium and NCCN recommend genetic counseling if: radiographic evidence of metastatic cancer exists; there is a Gleason score of at least 7 and a family history of disease; one or more relatives with ovarian or breast cancer was diagnosed at age 50 years or younger; or 2 or more relatives on the same side of the family were diagnosed with cancer, especially if that cancer was breast, ovarian, pancreatic, prostate, colorectal, or endometrial.2,3 Dr Cheng said oncologists should consider genetic counseling if relatives are known to carry cancer risk genes such as BRCA1 or BRCA2.

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“In men with metastatic disease, there is a new conversation around family history, genetic testing, and treatment implication that we are still figuring out how to do in the best way possible to serve patients and their families — guidelines are changing quickly and new models of care are needed,” she said. “It’s also important to be aware of these changes, to ask about the family history of cancer beyond prostate, to engage with genetic counselors, and to consider new models that facilitate timely testing if treatment decisions for metastatic prostate cancer are imminent.”

Dr Sartor said that while both publications address DNA-repair defects, “neither address genes such as HOXB13 that are potentially important for men and their families. Non-DNA- repair genes linked to risk of prostate cancer, like HOXB13, should be included in the panels used to assess men who have advanced and/or familial prostate cancer.”

That omission of the mention of HOXB13in the white paperwas intentional, Dr Cheng said.

“At present, HOXB13is not among the genes that would suggest a response or lack of response to DNA-damaging agents like PARP inhibitors or platinum. The potential treatment implications are less established, but there may be relevance in the cancer-screening setting,” Dr Cheng said, adding that it certainly warrants further investigation.

These recommendations for genetic counseling and germline-mutation testing “are some of the fastest discovery to clinical practice changes that I have ever seen,” Dr Simons said. 

References

  1. Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate CancerN Engl J Med.2016;375(5):443-453. doi: 10.1056/NEJMoa1603144
  2. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Prostate Cancer. Version 3.2018. www.nccn.org. Updated August 8, 2018. Accessed September 4 2018.
  3. Carlo MI, Giri VN, Paller CJ, et al for the Prostate Cancer Clinical Trials Consortium. Evolving Intersection Between Inherited Cancer Genetics and Therapeutic Clinical Trials in Prostate Cancer: A White Paper From the Germline Genetics Working Group of the Prostate Cancer Clinical Trials Consortium[published online August 16, 2018]. JCO Precision Oncology. doi: 10.1200/PO.18.00060