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Repeat Molecular Testing in Advanced Prostate Cancer

Insights From: Daniel Petrylak, MD, Yale University; Nicholas Vogelzang, MD, Comprehensive Cancer Center
Published: Friday, Mar 27, 2020



Transcript:

Nicholas Vogelzang, MD: One of the themes that you brought up was this idea of the tumor evolving. Can you describe how you think about this?

Daniel Petrylak, MD: Well, there are different points at which we’re administering treatment. There are different switch points in terms of how the imaging changes. In other words, if a patient goes from bone-only disease to then bone plus visceral. Because clearly by giving treatment you’re selecting clones, you’re selecting those cells that are sensitive to the drug that you’re administering, and you’re left with resistant cells.

So we’re now moving into the era of molecular targeting and molecular tests for our patients. When do we do these? Should we do these right at the beginning of treatment? Should we do these as the patients evolve on treatment? There was a very interesting article that came out of Memorial Sloan Kettering Cancer Center about microsatellite instability. And they looked at a series of patients with prostate cancer, and they found that the rate was about 3%, as what we would expect. But there were 6 samples, 6 patients with consecutive samples, and half of those patients developed microsatellite instability over time.

The question is, how often should we sample our patients? Again, an each treatment decision? Right at the beginning? Who’s going to pay for this because these are expensive tests? We’re developing these new tests, but we’re really evolving as to how we should use them and when we should use them.

Nicholas Vogelzang, MD: Are you using any of that in your practice?

Daniel Petrylak, MD: Yes, I am.

Nicholas Vogelzang, MD: What do you do?

Daniel Petrylak, MD: Initially we look at the patient. The question, of course, is there germline BRCA in our patients? And that has important implications for the entire family—the children, the sisters—do they have, are they susceptible to having breast cancer or other tumors that could be curable? Of course now genetic counseling is going to be very important in all of our patients as well.

The guidelines are basically not really distinguishing which of the patients we should be looking at genetically, and I think we do this in everybody now. We also get a good family history. But I’ve seen BRCA germline mutations in patients without a family history.

Nicholas Vogelzang, MD: Exactly.

Daniel Petrylak, MD: This is really a very important issue.

Nicholas Vogelzang, MD: Are you using the cell-free DNA at all, or does this mean that you rebiopsy patients?

Daniel Petrylak, MD: We try to biopsy when we can, and we do our own inhouse genetic testing at Yale University. It’s called Oncomine, which looks at the somatic mutations in tumor cells. We also look at germline as well in our patients because we want to know the family history, and there are tests that can be done on saliva that can tell us what the germline mutations are.

I basically try to think about the patient and how things have changed. And I’m looking for every opportunity to treat my patient with a drug that may impact their lives. If for example, their tumor gets more aggressive, I may repeat a CTC [circulating tumor cell], assay to look at their different genomes, or how things have changed.

Nicholas Vogelzang, MD: Are you using CTCs very much?

Daniel Petrylak, MD: We’re using the….

Nicholas Vogelzang, MD: CellSearch.

Daniel Petrylak, MD: CellSearch and those types of patterns as well. We’re looking at those particular things. The question is, what’s best? And then, of course, quality. Are you going to get the same answer from the same test? This is a heterogeneous disease, and you may get different answers by the different sampling techniques.

Transcript Edited for Clarity
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Transcript:

Nicholas Vogelzang, MD: One of the themes that you brought up was this idea of the tumor evolving. Can you describe how you think about this?

Daniel Petrylak, MD: Well, there are different points at which we’re administering treatment. There are different switch points in terms of how the imaging changes. In other words, if a patient goes from bone-only disease to then bone plus visceral. Because clearly by giving treatment you’re selecting clones, you’re selecting those cells that are sensitive to the drug that you’re administering, and you’re left with resistant cells.

So we’re now moving into the era of molecular targeting and molecular tests for our patients. When do we do these? Should we do these right at the beginning of treatment? Should we do these as the patients evolve on treatment? There was a very interesting article that came out of Memorial Sloan Kettering Cancer Center about microsatellite instability. And they looked at a series of patients with prostate cancer, and they found that the rate was about 3%, as what we would expect. But there were 6 samples, 6 patients with consecutive samples, and half of those patients developed microsatellite instability over time.

The question is, how often should we sample our patients? Again, an each treatment decision? Right at the beginning? Who’s going to pay for this because these are expensive tests? We’re developing these new tests, but we’re really evolving as to how we should use them and when we should use them.

Nicholas Vogelzang, MD: Are you using any of that in your practice?

Daniel Petrylak, MD: Yes, I am.

Nicholas Vogelzang, MD: What do you do?

Daniel Petrylak, MD: Initially we look at the patient. The question, of course, is there germline BRCA in our patients? And that has important implications for the entire family—the children, the sisters—do they have, are they susceptible to having breast cancer or other tumors that could be curable? Of course now genetic counseling is going to be very important in all of our patients as well.

The guidelines are basically not really distinguishing which of the patients we should be looking at genetically, and I think we do this in everybody now. We also get a good family history. But I’ve seen BRCA germline mutations in patients without a family history.

Nicholas Vogelzang, MD: Exactly.

Daniel Petrylak, MD: This is really a very important issue.

Nicholas Vogelzang, MD: Are you using the cell-free DNA at all, or does this mean that you rebiopsy patients?

Daniel Petrylak, MD: We try to biopsy when we can, and we do our own inhouse genetic testing at Yale University. It’s called Oncomine, which looks at the somatic mutations in tumor cells. We also look at germline as well in our patients because we want to know the family history, and there are tests that can be done on saliva that can tell us what the germline mutations are.

I basically try to think about the patient and how things have changed. And I’m looking for every opportunity to treat my patient with a drug that may impact their lives. If for example, their tumor gets more aggressive, I may repeat a CTC [circulating tumor cell], assay to look at their different genomes, or how things have changed.

Nicholas Vogelzang, MD: Are you using CTCs very much?

Daniel Petrylak, MD: We’re using the….

Nicholas Vogelzang, MD: CellSearch.

Daniel Petrylak, MD: CellSearch and those types of patterns as well. We’re looking at those particular things. The question is, what’s best? And then, of course, quality. Are you going to get the same answer from the same test? This is a heterogeneous disease, and you may get different answers by the different sampling techniques.

Transcript Edited for Clarity
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