Analyzing Real-World Impact of Race on ADT Mortality in Prostate Cancer - Judd Moul
February 27, 2024
Judd Moul discusses a study focusing on the mortality risk associated with androgen deprivation therapy (ADT) in Black versus white patients with prostate cancer. The study, a comprehensive analysis of a large cohort, indicates that African-American ethnicity may be protective for survival in both castrate-resistant and castrate-sensitive prostate cancer. This contradicts earlier perceptions, especially given the higher mortality rates generally associated with prostate cancer in Black men at earlier stages of the disease. The study also delves into factors like metastasis presence and body mass index, influencing survival outcomes. Dr. Moul's work, by examining a diverse population starting ADT, sheds light on racial disparities and survival benefits, inviting further investigation into the underlying causes and potential clinical implications of these findings.
Biographies:
Judd W. Moul, MD, Urologic Oncologist, Duke Health, Durham, NC
Samuel L. Washington III, MD, MAS, Urologist, Goldberg-Benioff Endowed Professorship in Cancer Biology, University of Southern California, San Francisco, CA
Biographies:
Judd W. Moul, MD, Urologic Oncologist, Duke Health, Durham, NC
Samuel L. Washington III, MD, MAS, Urologist, Goldberg-Benioff Endowed Professorship in Cancer Biology, University of Southern California, San Francisco, CA
Read the Full Video Transcript
Sam Washington: We're here at ASCO GU 2024. Thank you for taking the time to talk with us about your study, Dr. Moul, Professor of Urology at the Cancer Institute, Duke University.
Judd Moul: Thank you very much. It's really a pleasure and honor to be here.
Sam Washington: Very interesting study looking at the real-world mortality risk after initiation of androgen deprivation therapy in Black versus white patients. Can you tell me a little bit about the study?
Judd Moul: Right. So we had known, I think, for at least the last four or five years, that in men with castrate-resistant prostate cancer, once a patient gets to the state of castrate resistance, African-American ethnicity or race was a protective factor for survival in CRPC. And the first group to show that was Oliver Sartor's group with the PROCEED Registry, with PROVENGE. And then Susan Halabi, who's a biostatistician at Duke, she looked at the SWOG databases and showed a similar finding.
What our study does, for the first time, looks at a broader cohort of patients both with castrate-resistant and castrate-sensitive prostate cancer and shows that African-American race or ethnicity is protective for survival.
Sam Washington: Very interesting work with a large cohort to finally look at this. Did you see any differences between the Black and white men in terms of clinical characteristics, demographic data that may have contributed to some of the findings?
Judd Moul: That's a great question. We know that this was an administrative database. We had access to quite a few variables, although there's always the issue of are there variables that we missed? What we found was there were a number of factors that certainly contributed to this overall survival.
Now, this was a data set. The entry criteria was a patient who got one or more doses of ADT, so leuprolide primarily, or maybe degarelix, but that was the primary starting point. And 99% of the patients were treated between 2010 and 2020 so that was the period of time we were looking at. But since there's no ICD-9 code specifically for castrate-resistant prostate cancer, this could have included patients with locally advanced disease who were starting ADT, metastatic prostate cancer, and castrate-resistant. The biggest factor that predicted survival was mets versus no mets. Makes sense that, again, it was a co-mixture of patients who probably had ADT with radiation and then there were patients with metastatic disease. So that was the number one factor in multivariable analysis.
Interestingly, the second most important factor was body mass index. So that's potentially even more clinically relevant. And what it basically means is that, yeah, you're better off being thin for most of your life, but when you develop advanced prostate cancer, having some extra weight on board was actually protective. And when you think about it, that makes sense to me because what do men die of with prostate cancer? Most of them just get into this cachectic state and then eventually just pass away. So having that extra, if you will, meat on the bones, helped them live longer.
But even factoring in body mass index, race was still protective. And so, again, in the multivariable analysis, ethnicity or race was still protective, which we found extremely interesting. And the question is, why? What else is there that's making this relevant? Now, is it clinically significant? I guess the only thing we would say is certainly once you get to advanced disease, being Black or self-described as Black is not a negative factor. It doesn't contribute to worse outcomes. But again, it's going to be counterintuitive for some people who are used to all the data we've seen in earlier-stage disease.
Sam Washington: Right, and that's the interesting part, both the obesity paradox that we've seen in other cancers in the past where having a little bit of extra obesity, some higher BMI, is associated with better outcomes than a lower BMI in that clinical context, but with other cancers. But also the findings that you have here run, in this context, a little counterintuitive to what you would expect, given a lot of the other information out there, which is exciting.
Judd Moul: One of the things that we were excited to present this at GU ASCO. Obviously, there are so many great minds here, and one of my ulterior motives is asking people, "Help me explain this." And I know you work at UCSF with Mack Roach who's done a tremendous amount of work in this area. And what Mack told me this morning, and that's another thing I love about GU ASCO, it's a great opportunity to commingle and have these multidisciplinary discussions, Mack actually says that embedded in some of the RTOG and some of the other trials, they've seen this. But, to my knowledge, no one has written a specific paper just focusing on this broad cohort of men starting ADT and showed this. So I need to follow up with Dr. Roach and see if I can delve into some of that other literature to see, in fact, if that's the case.
Sam Washington: Yeah, because a lot of the ADT literature out now is focusing on the cognitive impact or cardiac impacts, and we have to remember that there are other aspects of this too. So it's exciting to see you guys dive into that aspect of ADT that we haven't really looked at as much in the past.
Judd Moul: One of the interesting things that's come up is this concept of perhaps we're culling out and left with a healthier cohort, and specifically that many African-American patients potentially pass from kidney disease. There's a higher risk of kidney failure, kidney disease, dialysis. Maybe there were more MACE events that occurred earlier, not related to ADT, but just major cardiovascular events. So once a patient gets to the age group in general where they're starting ADT, whether it be locally advanced or advanced, maybe we're left with a hardier subgroup of patients so that those African-American patients are just, in general, hardier than the Caucasian patients as a whole. But that's purely speculation. I think more work needs to be done to try to tease this out.
Sam Washington: Yeah, definitely, there's a group that has survived to the point of getting ADT.
Judd Moul: Right.
Sam Washington: It means they're navigating not only the physiological, metabolic, other causes of mortality, but also the systems and societal barriers that they've overcome to get to the point where they can get ADT.
Judd Moul: What's interesting to me though is that patients who get lost, patients who are non-compliant, patients who don't have health insurance, and patients who have distrust of the health system, there are a lot of African-American patients who don't get to the doctor and therefore when they're diagnosed with prostate cancer they're diagnosed at a more advanced stage. So I really think that, yet, this data set shows that they have a better survival than the Caucasian patients if you only mark time starting with that introduction of ADT.
Sam Washington: Yeah. Right.
Judd Moul: So it's just interesting and we need to get our head further around what we can do with that, what does it mean clinically? And further other questions, and then see if it translates into other therapeutics.
Sam Washington: But exciting times ahead. I'm glad we are starting to really dive into this, more than I can say that we've done in the last 20, 30 years. So thank you so much for taking the time out to chat with us.
Judd Moul: Thank you very much. I really appreciate it. Thanks.
Sam Washington: We're here at ASCO GU 2024. Thank you for taking the time to talk with us about your study, Dr. Moul, Professor of Urology at the Cancer Institute, Duke University.
Judd Moul: Thank you very much. It's really a pleasure and honor to be here.
Sam Washington: Very interesting study looking at the real-world mortality risk after initiation of androgen deprivation therapy in Black versus white patients. Can you tell me a little bit about the study?
Judd Moul: Right. So we had known, I think, for at least the last four or five years, that in men with castrate-resistant prostate cancer, once a patient gets to the state of castrate resistance, African-American ethnicity or race was a protective factor for survival in CRPC. And the first group to show that was Oliver Sartor's group with the PROCEED Registry, with PROVENGE. And then Susan Halabi, who's a biostatistician at Duke, she looked at the SWOG databases and showed a similar finding.
What our study does, for the first time, looks at a broader cohort of patients both with castrate-resistant and castrate-sensitive prostate cancer and shows that African-American race or ethnicity is protective for survival.
Sam Washington: Very interesting work with a large cohort to finally look at this. Did you see any differences between the Black and white men in terms of clinical characteristics, demographic data that may have contributed to some of the findings?
Judd Moul: That's a great question. We know that this was an administrative database. We had access to quite a few variables, although there's always the issue of are there variables that we missed? What we found was there were a number of factors that certainly contributed to this overall survival.
Now, this was a data set. The entry criteria was a patient who got one or more doses of ADT, so leuprolide primarily, or maybe degarelix, but that was the primary starting point. And 99% of the patients were treated between 2010 and 2020 so that was the period of time we were looking at. But since there's no ICD-9 code specifically for castrate-resistant prostate cancer, this could have included patients with locally advanced disease who were starting ADT, metastatic prostate cancer, and castrate-resistant. The biggest factor that predicted survival was mets versus no mets. Makes sense that, again, it was a co-mixture of patients who probably had ADT with radiation and then there were patients with metastatic disease. So that was the number one factor in multivariable analysis.
Interestingly, the second most important factor was body mass index. So that's potentially even more clinically relevant. And what it basically means is that, yeah, you're better off being thin for most of your life, but when you develop advanced prostate cancer, having some extra weight on board was actually protective. And when you think about it, that makes sense to me because what do men die of with prostate cancer? Most of them just get into this cachectic state and then eventually just pass away. So having that extra, if you will, meat on the bones, helped them live longer.
But even factoring in body mass index, race was still protective. And so, again, in the multivariable analysis, ethnicity or race was still protective, which we found extremely interesting. And the question is, why? What else is there that's making this relevant? Now, is it clinically significant? I guess the only thing we would say is certainly once you get to advanced disease, being Black or self-described as Black is not a negative factor. It doesn't contribute to worse outcomes. But again, it's going to be counterintuitive for some people who are used to all the data we've seen in earlier-stage disease.
Sam Washington: Right, and that's the interesting part, both the obesity paradox that we've seen in other cancers in the past where having a little bit of extra obesity, some higher BMI, is associated with better outcomes than a lower BMI in that clinical context, but with other cancers. But also the findings that you have here run, in this context, a little counterintuitive to what you would expect, given a lot of the other information out there, which is exciting.
Judd Moul: One of the things that we were excited to present this at GU ASCO. Obviously, there are so many great minds here, and one of my ulterior motives is asking people, "Help me explain this." And I know you work at UCSF with Mack Roach who's done a tremendous amount of work in this area. And what Mack told me this morning, and that's another thing I love about GU ASCO, it's a great opportunity to commingle and have these multidisciplinary discussions, Mack actually says that embedded in some of the RTOG and some of the other trials, they've seen this. But, to my knowledge, no one has written a specific paper just focusing on this broad cohort of men starting ADT and showed this. So I need to follow up with Dr. Roach and see if I can delve into some of that other literature to see, in fact, if that's the case.
Sam Washington: Yeah, because a lot of the ADT literature out now is focusing on the cognitive impact or cardiac impacts, and we have to remember that there are other aspects of this too. So it's exciting to see you guys dive into that aspect of ADT that we haven't really looked at as much in the past.
Judd Moul: One of the interesting things that's come up is this concept of perhaps we're culling out and left with a healthier cohort, and specifically that many African-American patients potentially pass from kidney disease. There's a higher risk of kidney failure, kidney disease, dialysis. Maybe there were more MACE events that occurred earlier, not related to ADT, but just major cardiovascular events. So once a patient gets to the age group in general where they're starting ADT, whether it be locally advanced or advanced, maybe we're left with a hardier subgroup of patients so that those African-American patients are just, in general, hardier than the Caucasian patients as a whole. But that's purely speculation. I think more work needs to be done to try to tease this out.
Sam Washington: Yeah, definitely, there's a group that has survived to the point of getting ADT.
Judd Moul: Right.
Sam Washington: It means they're navigating not only the physiological, metabolic, other causes of mortality, but also the systems and societal barriers that they've overcome to get to the point where they can get ADT.
Judd Moul: What's interesting to me though is that patients who get lost, patients who are non-compliant, patients who don't have health insurance, and patients who have distrust of the health system, there are a lot of African-American patients who don't get to the doctor and therefore when they're diagnosed with prostate cancer they're diagnosed at a more advanced stage. So I really think that, yet, this data set shows that they have a better survival than the Caucasian patients if you only mark time starting with that introduction of ADT.
Sam Washington: Yeah. Right.
Judd Moul: So it's just interesting and we need to get our head further around what we can do with that, what does it mean clinically? And further other questions, and then see if it translates into other therapeutics.
Sam Washington: But exciting times ahead. I'm glad we are starting to really dive into this, more than I can say that we've done in the last 20, 30 years. So thank you so much for taking the time out to chat with us.
Judd Moul: Thank you very much. I really appreciate it. Thanks.