Germline testing to assess risk for specific types of prostate cancer

The recommendations of the Philadelphia Prostate Cancer Consensus Conference 2019 (held in October last year) on implementation of germline testing for risk of prostate cancer have now been published in the Journal of Clinical Oncology.

The original conference and the related article by Giri et al. dealt primarily with recommendations for testing of the normal (“germline”) DNA of men who either have or are at significant risk for prostate cancer, and not with the testing of “somatic” DNA of particular cancerous cells available through some form of biopsy (of the prostate itself or of a specific metastatic tumor).

The full text of the article by Giri et al. is freely available on line, and so interested readers may study this for themselves. There is also a simpler commentary about the consensus report on the MedPage Today web site.

The key assertions that came out of the conference were divided into two groups:

  • “Recommendations”, which were assertions supported by ≥ 75 percent of the voting conference participants
  • “Considerations”, which were assertions supported by 50 to 74 percent of the voting conference participants

The most important points that came out of the conference were that:

  • All men with metastatic prostate cancer should consider testing for germline mutations.
  • All men with a family history of cancer suggesting hereditary cancer predisposition should consider testing for germline mutations.
  • A so-called “large gene panel” should be used for germline testing, with priority given to BRCA1/2 and DNA mismatch-repair (MMR) genes.
  • Testing for additional genes should be guided by personal or family history.

We should note that “only” about 12 to 17 percent of men who have metastatic prostate cancer actually have known, relevant germline mutations, Such mutations are most commonly found in DNA repair genes (e.g., BRCA1/2, CHEK2, ATM, PALB2, and DNA MMR genes). An even smaller percentage of men with localized prostate cancer (about 7 percent) have such mutations.

Consequently, while an individual patient’s mutation status can be very important with respect to decision making about that particular patient’s management options (including referral to clinical trials, and to active surveillance for men with localized disease), this is not going to be the case for the vast majority (> 80 percent) of men with prostate cancer. The fact that we have been able to modify and improve management strategies for small subsets of men with less common forms of prostate cancer (e.g., through the use of the PARP inhibitors) unfortunately has done little to help the majority of men who have the commonest forms of adenocarcinoma of the prostate.

Editorial comment: Your sitemaster wishes to clearly note that he is one of nearly 100 authors listed on this article. Any influence he may have exercised in the conference planning stages, during the actual conference, or in creation of the final content of the article in JCO is therefore (at best) limited.

One Response

  1. It should also be noted that most studies of the use of PARP inhibitors in prostate cancer have only shown promise for certain BRCA gene mutations. Other mutations in the BRCA pathway, like ATM, CHEK2 and PALB2 have rarely been actionable, although they have responded in other cancers like breast and ovarian.

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