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Tian Zhang: Welcome to this episode of UroToday. We're so excited at ASCO 2025 to be highlighting some really exciting prostate cancer molecular profiling work. I'm Tian Zhang. I'm a GU medical oncologist and associate director of clinical research at UT Southwestern in Dallas, Texas.

I'm really happy today to be joined with two very early career colleagues but really rising stars in our field, Dr. Sharon Choi at University of California, San Diego and Dr. Janie Qin, who is assistant professor at UT Southwestern with me. So welcome. Thanks so much for coming in.

Qian (Janie) Qin: Thank you for having us.

Tian Zhang: So really excited to see both of your work and coming at it from two different commercial profiling for men with prostate cancer. So, Sharon, yours is comprehensive genomic profiling of Black and non-Hispanic White men with prostate cancer. And Janie, yours, real-world prevalence of homologous recombination repair alterations and PARP inhibitor use and outcomes in patients with metastatic prostate cancer by race and ethnicity.

So I thought these were great to highlight together because they talk so much about prostate cancer, the need for molecular testing and what we're seeing in these subsets of populations that may not be so much enrolled into our clinical trials. So, Sharon, let's start with you. Tell us a little bit about what you were aiming to do with your analysis.

Sharon Choi: Sure. Thank you, Tian. It was a retrospective study. It was the largest study that we had involving non-Hispanic White and African-American patients with prostate cancer and looking at tissue molecular profiles and looking at differences. And it was basically a genomic landscape. And we correlated that with survival data, real-world survival data from insurance claims.

We also looked at treatment responses between non-Hispanic White subset and African-American patient subset. And we did see a little bit of a response between those two subsets in terms of different various treatments, namely enzalutamide. And we did see a numeric difference with PARP inhibition. So that's what we were aiming for to see if there was a difference, molecular difference between the two racial groups.

Tian Zhang: So did you see more people in Hispanic or Black populations have homologous recombination defects?

Sharon Choi: That's a great question. So in the overall cohort, we didn't see a difference. But if you looked at the metastatic, so this is all just metastatic tumors or biopsies or tissue sampling, we did see that there was a difference in homologous recombination alterations among African-American patients, but not at higher than non-Hispanic white patients but not in the primary prostate tissue specimen.

Tian Zhang: Interesting, OK. And I'm going to delve a little bit further and ask you when you said they have a little bit differences in efficacy and outcomes, which population did better or worse? And why do you hypothesize that might be?

Sharon Choi: That's a great question. So, we have data from Abi Race. We have data from PANTHER. So before we dived in, we questioned whether we could recapitulate those findings. Just looking at retrospectively, of course, it's not the same as a prospective trial, but we didn't see a significant difference with abiraterone.

However, with enzalutamide, we found that African-American patients had a longer time on treatment than non-Hispanic White patients. We also saw that African-American patients had a numeric longer overall survival on PARP inhibition than non-Hispanic White patients. But it wasn't statistically significant and that could be due to sample size.

Tian Zhang: Sure. That's, I think, really important to tease out for folks because from the Duke data, Abi Race was a prospective trial of Black versus non-Hispanic White patients treated with abiraterone, PANTHER being abiraterone with apalutamide. Those subsets of patients tend to potentially have differences in drug processing and metabolism. And so, would you be able to look in your subset more about not necessarily pharmacokinetics but a little bit more about pharmacogenomics or what other SNPs, for example, they had?

Sharon Choi: That's a great question. So I don't know if this is the platform to look into pharmacokinetics, but we did absolutely look into genomics. African-American patients had a higher prevalence of SPOP alterations, a lower prevalence of TP53, PTEN, CDK12. So that was quite interesting because as we know, TP53 and PTEN are unfavorable gene alterations.

However, if you look at the overall picture between non-Hispanic White patients and African-American patients, African-American patients had worse prognosis, points to that social determinants of health, outcomes are related to multifaceted determinants and rather than just genomics. But what is interesting is that we do find, we do capture elements that might benefit African-American patients, possibly more than non-Hispanic White patients. So that was an interesting finding.

Tian Zhang: And certainly highlights the point of testing for these patients.

Sharon Choi: Absolutely. That's been demonstrated that African-American patients, when we do genomic testing, there's a higher rate of VUSs, a variable, undetermined significance. And so I think that absolutely highlights and underscores the need for testing because we might be able to capture a treatment that favors this racial subgroup.

Tian Zhang: Fantastic. We'll turn our attention to Janie. Janie, tell us what you did with your cohort and who you work with and what you found?

Qian (Janie) Qin: There are some similarities in the two retrospective analysis. As Tian, you've mentioned, PARP inhibitor is monotherapy and in combination with ARPIs are now standard of care for metastatic castration-resistant prostate cancer and certainly coming into early lines of therapy with AMPLITUDE TALAPRO-3 into first-line hormone-sensitive prostate cancer. However, as you've also mentioned, racial ethnic minorities on these landmark trials represent less than 5% for non-Hispanic Black, maybe 10% to 15% for Hispanic Latino.

So I think these real-world data can really help us with looking at the utility of PARP inhibition in the clinical setting and also give us some idea of the generalization of our trial data into our clinic.

And so with that, our retrospective analysis used Guardant, so GuardantINFORM, which is a clinical genomic database with, again, administrative claim data and liquid biopsy. And so it's the Guardant CDx, which includes five major alterations, BRCA1/2, ATM, I think CDK12 and MLH1 and the LDx which has four additional HRR alterations. And so we looked at patients who had a Guardant liquid biopsy between 2014 to 2024, who also has claims data and has received at least one line of systemic therapy after their liquid biopsy.

And so with that, we're looking at the prevalence of HRR alterations overall and then focusing also on BRCA1/2. We looked at PARP inhibitor use overall as monotherapy and in combination. And then we looked at real-world overall survival based on the time that they started their therapy after liquid biopsy to time of death for any cause.

And so with that, we actually identify, I think, over 30,000 patients who had a liquid biopsy, of which around I think 3,200 were non-Hispanic. So then we subdivide into non-Hispanic White, non-Hispanic Black and Asian and Other and then Hispanic Latino. So there's over 3,000 in non-Hispanic White, I think about 380 or 330 for Hispanic Latino, 481 for non-Hispanic Black and then 181, I believe, for Asian/Other for the five mutations. And then for the nine mutations, it was a subset of those patients, so about 14,000 total and then a little over half in terms of each racial ethnic minority.

And so we then looked at first kind of HRR alteration across with the LDx versus the CDx panel of HRR alterations. For the LDx, we did note that with the nine alteration, there is significantly higher alteration rate for non-Hispanic White patients compared to non-Hispanic Black and Hispanic Latino. So I think it was 22.8% versus 18.1% versus 19.6%, which was a statistically significant based on the large number of patients that we had.

Looking at the smaller cohort of CDx, I think the non-Hispanic White patients also had a higher prevalence of HRR alterations compared to non-Hispanic Black patients. So that was the first finding that was interesting, of which we particularly looked at BRCA1/2, which the prevalence was very similar. It was around 5.2 to 5.8% across race and ethnicity, which is, I think, important and impactful because we know based on all the prior trials, PARP inhibition seems to work very well for BRCA1/2 versus other HRR alterations.

The other thing that I find interesting is the prevalence of PARP inhibitor use was actually equal across the different racial ethnic minorities, which tells us there's equality of treatment once patients get the liquid biopsy. It doesn't answer the question of before the liquid biopsy, is there equality of getting the local biopsy? But once they do, there's some equality of treatment with PARP inhibitors, which is around high 20s percentage across the board. But BRCA1/2 is much higher. It was high 30s to low 40s percentage-wise with PARP inhibition use.

The other thing that we found interesting that kind of echoes Abi Race and PANTHER was that interestingly, the non-Hispanic Black patients using PARP plus ARPI actually had more favorable outcome compared to non-Hispanic White patients. And so again, speaking to that potential underlying biology, do our non-Hispanic Black patients respond more to androgen inhibition or not? And so that obviously, it's hypothetical, hypothesis generating with retrospective study. But I thought it was a very interesting point.

Tian Zhang: It's great, wonderful summary. So a lot of the power in these real-world data comes in the larger data sets and people that we don't necessarily have on trials. But to both of your points, accessing the molecular profiling, getting them on treatment all really important. And so tell us about your own practice of how do you-- a patient comes in with metastatic hormone-sensitive prostate cancer or castration resistance. Where in your practice are you testing, and do you test multiple times? What's your practice like?

Sharon Choi: I guess I'll go first. So my practice is if they're metastatic disease, if I have access to the tissue specimen, I test it just because we have this emerging information. And there might be a time where we don't have that archival tissue. So I try to optimize the opportunity to get some molecular information if I have access to the specimen.

And then for ctDNA, circulating tumor DNA, I do collect that information on progression. That's my practice and then germline, of course.

Tian Zhang: You'll try to find treatment resistance.

Sharon Choi: Absolutely, yes.

Tian Zhang: Great, Janie.

Qian (Janie) Qin: Yeah, very similar. I say every patient that walks through my door with prostate cancer probably gets both somatic and hereditary testing because most of the time, they're either metastatic, which is why they're seeing a medical oncologist. Or they could be high risk, very high-risk localized. For either reason, we should be doing molecular testing.

So similar to what you do, I certainly send it on the tumor tissue if we have it for the somatic piece. If we don't, I do the liquid biopsy up front as well and then at progression. And then the hereditary piece, we usually send to our genetic counselor. And then they send off the test because, as PARP inhibitors come to earlier lines, first-line metastatic CRPC. If they have HRR alteration, we could technically use combination with enhanced hormone therapy.

And so I think it's important, especially because that first-line CRPC is also getting quite crowded, right, with PSMAfore Pluvicto coming into pre-taxane radium plus enzalutamide. And so I think there's a lot that we have to think about for that first-line CRPC. And so having the data beforehand can really help us in terms of determining that first line. And these take time. They take two or three weeks to come back. And so it's always good to have that on hand. And then I tend to repeat liquid biopsy at progression to see if there's any changes and alteration.

We also have investigator-initiated trials at UT Southwestern. It's actually Dr. Zhang and I's looking at PARP in the first-line setting. So even more reason, I wish our urologists or radiation oncologists would send them. So we have that data for our first line ITs. But yeah, I think everybody that comes to the door are really order both.

Tian Zhang: Sure. And to the point of finding it early and finding those patients who have actionable mutations--

Sharon Choi: Absolutely.

Tian Zhang: --and getting them on treatment, this year's ASCO will also see the AMPLITUDE data for metastatic hormone-sensitive prostate cancer treated with niraparib, abiraterone. So really excited to see that data. And what you all are doing is really key in providing that real-world evidence of what are the subsets of patients doing and what are those smaller populations but really key populations, and how can we treat them potentially with an AMPLITUDE type approach of using those PARP inhibitors early on in the disease course? So really excited for you guys.

Last question on my end but you both represent the newest generation of women in prostate cancer and clinical oncologists. So can you share with our audience what led you to academic oncology and being in the prostate cancer field, and what challenges or obstacles do you foresee or are you excited about?

Sharon Choi: Well, I became a medical oncologist by the virtue of my basic science background. I felt like that was my natural niche since medical school. And so I kind of delved into it, went down that route. And then in terms of prostate cancer is really just a patient population.

Part of our training at UCSD is at the VA. And so finding that patient and being very satisfied and with among the continuum of prostate cancer, I mean, it's just so broad. And then there are the subtypes. And so that was what was also fascinating and also the chance of cure. We're now in a space where we can potentially cure metastatic prostate cancer. And so that's what really drew me to that disease space. And also, the treatment options were hormonal therapy, targeted therapy. And then now we have radioligand therapy coming up in closer, closer. So I really like the multifactorial treatment options.

And so as a female oncologist within GU oncology, I really enjoy my mentors. I really enjoy learning from my female colleagues. I feel like there's a particular personality who enters GU medical oncology. And so I think that we really meld when we come together. I think that we should have more opportunities to gather and exchange information. Tian, you do a great job in arranging women in GU oncology at the annual meetings. And so I would really advocate for that.

Tian Zhang: Yeah, fabulous. Janie?

Qian (Janie) Qin: Yeah, no, I really echo a lot of what has been said. I actually went into fellowship thinking I'll be a malignant hematologist, which is very far from GU medical oncology. But it's truly the mentors that really guides us. And so I had the most wonderful mentors during fellowship.

And in fact, I actually asked my main mentor at the time, "Is it odd for a woman to go into GU?" And he said, "Absolutely not." And he listed 10, 15 different women in GU mentors. And he said, "I can connect you with them." I think Alicia Morgans, Maha Hussain, Tian Zhang, the list goes on. And so, he really gave me the confidence to say if this is what I love to do, then this is what I should do. And so I went in and never looked back.

The amount of research and amount of new therapies is also fantastic. Things we've learned in fellowship is not relevant to a degree. And so I think that's also very exciting. I always tell my patients, "I need to keep you living long enough with good quality of life for that next treatment to come out, and the next treatment is coming out." And so I think that's what pushes us to do clinical. And it's what's pushing us to do research, and so yeah, so yeah.

Tian Zhang: I love that. And there's so many exciting treatments for our patients across GU cancers and prostate cancer. There's antibody drug conjugates coming and bispecific T-cell engagers and more radioligand therapies. So much to come and hopefully so much more for our patients. And thank you for what you do and bring to the field. And with that, we'll wrap. And thank you so much for coming today.

Sharon Choi: Thank you for having me.

Qian (Janie) Qin: Thank you for having us.