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 under-reported population, and the management of these patients warrants further research.