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Home » Testosterone » Risk of Castration-Resistant Prostate Cancer Linked to a Genotype – Renal and Urology News

Inheritance of the adrenal-permissive HSD3B1 genotype in men with low-volume metastatic castration-sensitive prostate cancer (mCSPC) is associated with development of earlier castration-resistant disease and shorter overall survival, according to a new study.

Thegenotype augments extragonadal dihydrotestosterone synthesis, and previousresearch has suggested an association between the adrenal-permissive allele andearly development of castration-resistant prostate cancer (CRPC), investigatorsinvolved in the new study noted in a paper published in JAMA Oncology.

Thenew findings may enable clinicians to identify patients more likely to benefitfrom escalated androgen receptor axis inhibition beyond gonadal testosterone suppression,a team led by Nima Sharifi, MD, of Cleveland Clinic, concluded.

DrSharifi and colleagues analyzed the association between HSD3B1 (1245A) allele and early development of CRPC usingprospective data from CHAARTED (E3805 Chemohormonal Therapy vs AndrogenAblation Randomized Trial for Extensive Disease in Prostate Cancer), amulticenter phase 3 trial of androgen deprivation therapy with or withoutdocetaxel therapy in men with newly diagnosed mCSPC. Of 790 men randomized inthe trial, 527 had available DNA samples. Dr Sharifis team retrospectivelydetermined the HSD3B1 germlinegenotype in 475 white men (in whom the frequency of the adrenal-permissiveallele is highest) and analyzed clinical outcomes by genotype.

Ofthe 475 men, 270 (56.8%) inherited the adrenal-permissive genotype allele,whereas 205 had the adrenal-restrictive genotype, which limits extragonadaldihydrotestosterone synthesis. Among men with low-volume disease, theproportion of patients without CRPC at 2 years was significantly smaller amongthose with the adrenal-permissive than adrenal-restrictive genotype (51% vs70.5%), Dr Sharifis team reported. The overall survival rate at 5 years also wassignificantly worse in the group with the adrenal-permissive genotype (57.5% vs70.8%).

Comparedwith the adrenal-restrictive genotype, the adrenal-permissive genotype wassignificantly associated with a nearly 1.9-fold increased risk of CRPC and1.7-fold increased risk of death. The investigators found no associated betweengenotype and outcomes among men with high-volume disease.

Takentogether, our findings suggest that the HSD3B1genotype can be used to risk stratify white men with low-volume metastaticprostate cancer, Dr Sharifis team concluded. Those with the adrenal-permissivegenotype have a worse prognosis inasmuch as they develop CRPC sooner and haveshorter overall survival than men with the adrenal-restrictive genotype. Thisinformation could assist clinicians in counseling patients and guideresearchers in identifying those for whom escalated androgen receptor axisinhibition beyond mere gonadal testosterone suppression is most warranted.

Reference

HearnJWD, Sweeney CJ, Almassi N, et al. HSD3B1genotype and clinical outcomes in metastatic castration-sensitive prostate cancer.JAMA Oncol. 2020;6(4):e196496.doi:10.1001/jamaoncol.2019.6496

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Risk of Castration-Resistant Prostate Cancer Linked to a Genotype - Renal and Urology News

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Home » Testosterone » Risk of Castration-Resistant Prostate Cancer Linked to a Genotype – Renal and Urology News