The role of endogenous testosterone in de novo prostate cancer pathogenesis in humans remains unclear. The effect of testosterone on the tumor genome is not explored. To explore the correlation between perioperative testosterone level on genomic risk score in a cohort of men who underwent radical prostatectomy.
We included patients who underwent radical prostatectomy (2013-2018) & have (positive margin, and/or pT3a or higher). The outcome of interest was the GRS: low (<0.45), intermediate (0.45-0.6), & high (>0.6). The associations between serum testosterone level and 188 gene expression-based signatures were examined. Secondary outcomes of interest included biochemical recurrence & receipt of secondary treatment.
The median GRS score was lower in the low testosterone group compared to the intermediate & normal testosterone groups (0.38 Vs. 0.52 Vs. 0.53, respectively; p=0.049). There was no difference in BCR-free survival between the three testosterone groups (p=0.9). Patients with low testosterone levels had higher odds of receiving secondary treatment (OR: 2.27; 95% CI: 1.14-4.50; p=0.02) than those with normal levels. A total of 43 (of 188) gene expression signatures were associated with testosterone level (p <0.05). In total, 33 signatures were positively associated with serum testosterone levels, including 12 signatures involved in DNA repair pathways.
This is the first study to assess the correlation of preoperative testosterone level on the tumor transcriptome and showed that no clinical correlation between pre-defined GRS groups and testosterone groups. This study adds to the notion of the limited role of endogenous testosterone on the development of de novo high-risk localized prostate cancer.
The Journal of urology. 2022 Jan 20 [Epub ahead of print]
Mohammed Shahait, Joseph G Cheaib, Elai Davicioni, Yang Liu, Ibrahim Abu Ghaida, Ryan W Dobbs, Mohamed Alshalalfa, Priti Lal, Daniel J Lee, David I Lee
Department of Surgery, King Hussein Cancer Center, Amman, Jordan., Department of Urology, Johns Hopkins University, Baltimore, Maryland., Veracyte, San Francisco, California., Department of Radiation Oncology, Burjeel Cancer Center, Abu Dhabi, UAE., Department of Surgery, Cook County hospital., Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California., Department of Pathology, University of Pennsylvania, Philadelphia, Pennsylvania., Division of Urology, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.