Survival of Men with Metastatic Hormone-Sensitive Prostate Cancer and Adrenal-Permissive HSD3B1 Inheritance - Beyond the Abstract

There is now a plethora of mechanistic and clinical evidence that the adrenal-permissive HSD3B1 allele allows for prostate cancer to increase the synthesis of potent non-gonadal androgens.

Further, the 50% of men who inherit this allele have more rapid hormone therapy resistance and shorter overall survival after treatment with testicular androgen suppression. The current study shows, using level 1 data from the ENZAMET randomized phase 3 clinical trial, that the poor outcomes for these men are not inevitable. Instead, upfront blockade of the effects of adrenal androgens allows these men to have increased overall survival compared with the other 50% of men who do not inherit this hyperactive allele that otherwise is associated with poorer outcomes and shorter overall survival. Overall, this is a major step forward in understanding the genetics of prostate cancer and how that could be used to improve therapy for individual men.

Written by: Nima Sharifi, MD, Scientific Director, Desai Sethi Urology Institute, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida

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