Opinion
Video
Nima Sharifi, MD, on OS in CRPC associated with adrenal androgens, HSD3B1 gene
Author(s):
“Of the 3 adrenal androgens, it's DHEA that seems to be most indicative of overall survival,” says Nima Sharifi, MD.
In this video, Nima Sharifi, MD, shares key findings from the study, “Adrenal androgens and overall survival (OS) in men with castration-resistant prostate cancer (CRPC) treated with enzalutamide without (ENZ) or with abiraterone and prednisone (ENZ/AAP) (Alliance),” which he presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California.
Sharifi is a professor and the scientific director at the Desai Sethi Urology Institute of the University of Miami in Florida.
Video Transcript:
The Alliance study, this is a study of men who have castration resistant prostate cancer and are treated either with enzalutamide or a combination of abiraterone plus enzalutamide. We looked at 2 things in this particular study among other parts of the study. One is we looked at circulating concentrations of adrenal androgens. Adrenal androgens are non-gonadal, and they're basically the substrate that tumors use to make potent androgens and drive castrate resistant disease. We looked at 3 adrenal androgens: that's DHEA, androstenedion, and testosterone. We simply asked the question, "is there an association between circulating adrenal androgens and overall survival?" The answer to that part of the question is yes. Of the 3 adrenal androgens, it's DHEA that seems to be most indicative of overall survival. The takeaway there is that men who are in the lower third of DHEA, they have the worst outcomes. That's looking at associations with circulating adrenal antigens.
The second part of the study is to look at the genetics of HSD3B1, that gene that can be hyperfunctioning and essentially confer higher androgen biosynthesis. The takeaway for this part of the study is that men who inherit 2 copies of this hyperactive form of HSD3B1 seem to have a bit worse overall survival compared with everybody else. It's hard to comment on the statistical significance of this. Overall survival is 30 months compared with 35 months for men who don't inherit 2 copies of the allele. But that finding, the association of genetics vs clinical outcomes, is consistent with other retrospective data that were published previously. So, this, I think, mimics that other data.
This transcript was AI generated and edited by human editors for clarity.
