Targeting PSMA in Advanced Prostate Cancer - Episode 3

Differentiating Somatic and Germline Testing in PC

April 6, 2021
Ulka Vaishampayan, MD

,
Oliver Sartor, MD

Ulka N. Vaishampayan, MD, discusses somatic and germline genetic testing for patients with advanced prostate cancer.

Ulka N. Vaishampayan, MD: For most therapies that we have, we are not really using any genomic biomarkers to decide on these treatments. What we are using are the clinical characteristics of the patient—their age, health, and comorbidities—as well as of the tumor; specifically, tumor sites of metastases. All those are being factored in when we make treatment decisions. Do you think we are looking at any other things? 

Oliver Sartor, MD: We’re going to be talking a little later about phenotypic biomarkers. They’re about to come into the fore. Ulka, would you go through genetic testing, both germline and somatic, and talk a little about when it’s appropriate? Let me hear from you and the vast Michigan experience on genetic testing. That will be great to understand better.

Ulka N. Vaishampayan, MD: It is getting more and more important for all clinicians involved in the management of prostate cancer to understand and be able to order these tests of both germline mutations for therapeutic purposes and to find out whether the patients have a hereditary predisposition to cancer. 

As Oliver mentioned, a lot of the homologous recombination repair gene mutations, so BRCA1 and BRCA2 being the more typical ones, but there are others, like ATM, JAK2, PALB2, etc, would be candidates for PARP inhibitor therapies.

It helps us define the genetic transmission of potential cancer and have family members tested when we test the germline mutations. It also helps us decide who would be a candidate for PARP inhibitors, platinum chemotherapy, etc.

Similarly, as was mentioned before for microsatellite instability and mismatch repair deficiency, it is important to suggest and show responses to PD-1 inhibitors like pembrolizumab for tumor mutation burden. Those are cases where we have FDA approvals now just based on the genomic findings.

I want to bring up the point of germline mutations, which are inherited mutations or something you’re born with, as compared with the other type of mutations or genomic testing you can order. It’s on tumor tissue. It is considered somatic or acquired mutations within only the tumor tissue. Both are important. If you get a BRCA1 or BRCA2 mutation seen in the somatic tissue that you send for genomic testing, it may be important to discuss germline genetic testing with the patients. 

At present, NCCN [National Comprehensive Cancer Network] Guidelines recommend genomic testing at the time of initial diagnosis of even prostate cancer. You should be thinking about when to do genomic testing and what kind. The criteria include a positive family history of any type of cancer. Also, anybody with metastatic prostate cancer or high-risk locally advanced disease, regardless of family history, is eligible for genomic testing. 

Similarly, intraductal histology, which is a rarer histology in prostate cancer, should also be considered for genomic testing. You don’t have to necessarily wait until you’ve exhausted standard therapy options to start considering genomic testing.

Transcript edited for clarity.