Nima Sharifi, MD, on the link between HSD3B1 and OS in prostate cancer

In this video, Nima Sharifi, MD, shares key findings from the study, “HSD3B1 and overall survival (OS) in high-risk non-metastatic (M0) and metastatic (M1) prostate cancer starting androgen deprivation therapy (ADT) in the enzalutamide (ENZ) and abiraterone acetate plus prednisolone (AAP) STAMPEDE phase 3 trial,” 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:

That study is based on some basic mechanistic work on this gene, HSD3B1, in which half of all men inherit a hyperfunctioning form of this enzyme that drives androgen biosynthesis from non-testicular precursor steroids and allows tumors to become resistant to castration more quickly. There's a wealth of clinical data out there showing that men, specifically men with low volume metastatic castrate-sensitive prostate cancer, when they inherit this enzyme, they progress more quickly; they have shorter overall survival.

This study specifically, in STAMPEDE, looked at a randomized phase 3 clinical trial out of the UK that randomized men to either standard of care, which is basically medical castration, vs medical castration plus abiraterone plus enzalutamide, all in the setting of castrate-sensitive prostate cancer, non-metastatic disease, M1 low volume and M1 high volume. We hypothesized based on prior work that specifically men with low-volume disease, if they inherit this hyperactive form of HSD3B1, they'll have shorter overall survival. It turns out that that's true. We see that signal across the entire cohort.

There are 2 observations based on these data. One is that these outcomes in men treated in standard of care arm, meaning medical castration, that validates prior data that we published in CHAARTED. The second thing, which is perhaps a bit surprising, is that when you inherit this hyperfunctioning form of the enzyme, HSD3B1, even men who get more intensive therapy with medical castration plus enzalutamide plus abiraterone continue to have worse overall survival. So, getting that intensified therapy doesn't appear to reverse the outcomes. A bit surprising, but I think something that we need to understand much better.

This transcript was AI generated and edited by human editors for clarity.