HSD3B1 Linked to Poor Outcomes in Low-Volume Prostate Cancer

A study led by Nima Sharifi, MD (Hearn, Jama Oncol, 2020) found the adrenal-permissive HSD3B1 allele is associated with earlier castration resistance and shorter overall survival among men with low-volume metastatic prostate cancer. These findings lay the foundation for more personalized and effective prostate cancer treatment.

Sharifi and collaborators retrospectively examined data from 475 men enrolled on the multi-center, E3805 Chemohormonal Therapy vs Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) phase 3 trial testing docetaxel treatment in men with newly diagnosed metastatic prostate cancer. The team analyzed clinical outcomes by genotype, and found an association between inheritance of the adrenal-permissive genotype allele HSD3B1(1245C) and earlier resistance to treatment and shorter overall survival in men with low-volume metastatic prostate cancer. There was no observed association between genotype and outcomes among men with high-volume disease, and no interaction between genotype and benefit from docetaxel.

Sharifi, director of the Center for GU Malignancies Research at Cleveland Clinic Lerner Research Institute and Program Leader of the Case Comprehensive Cancer Center's GU Malignancies Program said, “These findings lay the groundwork for more personalized and effective treatments for prostate cancer,” in a press release. “If men carry this specific testosterone-related genetic abnormality we may be able to individualize their therapy.”

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