Dr Neeraj Agarwal on Knowledge Gaps and Genomic Testing in Prostate Cancer

Neeraj Agarwal, MD, a researcher and clinician at the University of Utah Huntsman Cancer Institute, discusses knowledge gaps and the importance of genomic testing in prostate cancer.

Transcript

What knowledge gaps remain in genomic testing and biomarker development in prostate cancer?

The biggest issue here is patients not being tested for biomarkers. So before we talk about what knowledge gaps there are in genomic testing, I think we need to test all patients first, and then talk about the gaps. As we know, olaparib and rucaparib are 2 PARP inhibitors currently approved for patients with advanced prostate cancer. Olaparib is approved for patients who are progressing on novel hormonal therapies, and rucaparib was approved for patients who are progressing on novel hormonal therapies and chemotherapy. So any patient with those eligible mutations are eligible for treatment with PARP inhibitors. But how many patients are actually being tested for those mutations?

So the answer is we do not know yet, because the drugs just got approved. But based on the data, we have, less than half of the patients are being tested. In fact, in the PROfound trial, which led to approval of olaparib, 30% of patients were not even eligible to screen for the trial because tissue was not available for testing. So I think the biggest gap here is we need to test these patients as soon as we see them in the clinic for the first time we see them in the clinic. When we order CT scans, we order bone scans, and order laboratory data, I think we should order comprehensive genomic profiling of the tumor. And depending upon the resources, refer to the high-risk genetics clinic or germline testing at the same time for all patients with prostate cancer. I think that's a first barrier I see before we identify more gaps.

And the second knowledge gaps are why patients do not respond in similar fashion. Why is response to PARP inhibitors in patients with prostate cancer with BRCA1 mutation, for example, not as robust as we see in patients with ovarian cancer who have BRCA1 mutation? Why for BRCA2 mutation, do we have differential responses for patients who have heterozygosity for BRCA1 loss versus homozygosity for BRCA2 loss? So I think there are a lot of questions which can be answered. But the first step would be to test all these patients, so that we know at least what is going on in the majority of the patients. And not only to answer these scientific questions, but also to make these oral pills which are so much more tolerated than contemporary chemotherapy, which are the other options in the study. So I think testing the patients is the biggest gap we have, and we need to test everyone we see them on the first or second time.