Alicia Morgans: Hi, I'm so excited to be here at SOGUG 2022, where I have the good fortune to speak with Dr. Enrique Gonzalez-Billalabeitia. Thank you so much for being here with me today.

Enrique Gonzalez-Billalabeitia: Thanks to you for having me.

Alicia Morgans: Wonderful. Today, you talked about molecular testing, which is so important in prostate cancer, and I'm wondering how you can really help us to just set the stage. Why do we do it? When do we do it? What do you think about in terms of molecular testing?

Enrique Gonzalez-Billalabeitia: I think that there are two things that we have to bear in mind with these patients. One is that they can identify this molecular testing, the additional treatment for these patients, they can benefit from. And on the other hand, there's some germline mutations. And we have to bear in mind that the family can also benefit. If we are talking about patients with advanced or high-risk, localized, or metastatic castration prostate cancer.

Alicia Morgans: Absolutely. So family testing and family implications can be really important if we find an alteration in the germline for a patient. But, of course, for therapeutics as well. In Spain, which is where you practice, are you testing in the metastatic hormone-sensitive setting? Are you testing for metastatic castration-resistant prostate cancer? When are you doing these tests to really think about a therapeutic approach for patients?

Enrique Gonzalez-Billalabeitia: Yeah, we think that the earlier, the better, so the earlier we know that the mutation is there. Actually, we usually go to identify some of the mutations upfront if the patient has no family history of prostate cancer. We try to do it earlier and to plan if the patient is a candidate for clinical trials or can benefit to participate in other trials. We try to do it earlier usually in hormone-sensitive metastatic prostate cancer.

The indication for PARP inhibitors in castration-resistant prostate cancer. We prefer to do it the earlier, the better, in the metastatic hormone-sensitive stage. But if we want to adjust to the indication, this treatment with PARP inhibitors is indicated in patients that are resistant to castration. So, that's the scenario where we will definitely need to do it. But if we can do it upfront, it can also help us to identify patients without a family history that will harbor also a germline mutation, so we try to do it the earlier, the better.

And on top, it can also help us to identify probably adequate sequences for treatment in these patients.

Alicia Morgans: Absolutely. And I think that, as you said the earlier we do it, we can plan out more clearly how we want to move forward in the metastatic CRPC setting. Right before we started recording, we talked briefly about how the CHMP actually gave a favorable opinion of the combination of abiraterone and olaparib in the PROpel trial for patients with metastatic CRPC. This could really upend a lot of what we do, and I wonder what are your thoughts? Do we still need to do genetic testing if it's an all-comers population that may benefit?

Enrique Gonzalez-Billalabeitia: That's a very interesting question. The CHMP has given a positive opinion on the combination of abiraterone and olaparib in all comers without selecting for the presence of germline defect or somatic defects in BRCA2 or BRCA1 or other HR genes.

But the thing is that, we still need to see more data regarding overall survival, and we still need to understand how the mechanism works in our commerce. I think that this is the second trial that demonstrates benefit in this situation, but still without overall survival, I think we need to be careful on this scenario.

Alicia Morgans: If you had to sum up your recommendations for molecular testing for patients with prostate cancer, what would they be?

Enrique Gonzalez-Billalabeitia: I think that all patients with metastatic prostate cancer need to have testing for the presence of HR genes, especially BRCA2 and BRCA1 but also other genes that could be also in germline, so that we can, in the tumor, have some information regarding if the patient needs additional testing, especially if they don't have a family history, and they're not too younger or something that really raises up the indication for germline testing.

And on top of that, we need also to identify mismatch repair genes. I think that there is 2% of patients that harbor these alterations and also one in five of these patients also can be germline even though they don't have a family history. So, this is something that we need to bear in mind.

And on top of this, I think that we need to re-biopsy these patients, looking for the neuroendocrine differentiation so that these patients could benefit additionally from other therapies including platinum combinations. And these are mostly the major recommendation for this patient with metastatic disease on top of also germline testing in case that we have any doubts that they could be or even though the testing in the tumor is negative, but still there is a family history that is strong enough so that we shouldn't be very confident only with the somatic information because this is small subset of patients that could harbor germline mutations that are not identified in the somatic tumor.

Alicia Morgans: Wonderful. Well, thank you for summing up so many of these concepts that you really discussed so expertly today at SOGUG. And I sincerely appreciate your time and always appreciate your expertise.

Enrique Gonzalez-Billalabeitia: Alice, thank you so much for having me.