The U Shape of Prostate-specific Antigen and Prostate Cancer-specific Mortality in High-grade Metastatic Prostate Adenocarcinoma

Background: Accumulated evidence suggests that metastatic prostate cancer (mPCa) with a low prostate-specific antigen (PSA) level may be a unique entity. However, its clinical features and prognosis have not been fully evaluated. Objective: To investigate the clinical features of low-PSA mPCa and the impact of low PSA level on overall survival (OS) and PCa-specific mortality (PCSM) of mPCa. Design, setting, and participants: A total of 8479 mPCa patients were retrieved from the Surveillance, Epidemiology, and End Results program (2010-2015). The median follow-up was 18 mo. Outcome measurements and statistical analysis: Cox regression and Fine-Gray competing risk were used to calculate the hazard ratio (HR) and subdistribution hazard ratio (sHR) for OS and PCSM, respectively. Results and limitations: A higher rate of T4 stage disease (19.8%) and visceral metastasis (18.2%) and the shortest median OS (34 mo) were observed in mPCa patients with Gleason 8-10 and PSA <= 4 ng/ml. In the Cox regression model, PSA <= 4 ng/ml was a significant predictor of OS for Gleason 8-10 disease. The distribution of PCSM by PSA was U-shaped for Gleason score 8-10 (PSA 4.1-10 ng/ml as the referent), with an adjusted sHR of 1.52 for PSA <= 4.0 ng/ml (95% confidence interval: 1.17-1.96) versus 0.99 for PSA 10.1-20 ng/ml and 1.35 for PSA >20 ng/ml. In contrast, the distribution of PCSM by PSA was linear for Gleason 5-7. Sensitivity analyses showed similar results in Gleason 9-10 and Gleason 10 subgroup. The study is limited by its retrospective design. Conclusions: Low PSA, high-grade mPCa has a higher proportion of T4 stage disease, visceral metastasis, and PCSM. Patient summary: We found that 2.8% of high-grade metastatic prostate cancer has a prostate-specific antigen level <= 4 ng/ml at diagnosis. This population has aggressive clinical features and a poor cancer-specific outcome. Our results highlighted this underreported population, and the management of these patients warrants further research. (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.