Association of very low prostate-specific antigen levels with increased cancer-specific death in men with high-grade prostate cancer

BACKGROUNDThe objective of this study was to determine whether a very low presenting prostate-specific antigen (PSA) level was associated with greater prostate cancer-specific mortality (PCSM) among men with a Gleason score (GS) of 8 to 10. METHODSThe Surveillance, Epidemiology, and End Results program was used to identify 328,904 men diagnosed with clinicalT1 (cT1)-4N0M0 prostate cancer between 2004 and 2010. A multivariate Fine-Gray competing risks regression analysis was used to determine PCSM as a function of the PSA level (2.5, 2.6-4, 4.1-10, 10.1-20, 20.1-40, or>40ng/mL) and GS (8-10 vs7). RESULTSThe median follow-up was 38 months. Among men with GS 8-10 disease, with a PSA level of 4.1 to 10ng/mL as the referent, the adjusted hazard ratio for PCSM for men was 2.15 with a PSA level2.5ng/mL (95% confidence interval [CI], 1.65-2.79; P<.001), 1.60 with a PSA level of 2.6 to 4ng/mL (95% CI, 1.22-2.10; P=.001), 1.60 with a PSA level of 10.1 to 20ng/mL (95% CI, 1.41-1.82; P<.001), 2.08 with a PSA level of 20.1 to 40ng/mL (95% CI, 1.81-2.38; P<.001), and 3.23 with a PSA level>40ng/mL (95% CI, 2.85-3.65; P<.001). This suggested a U-shaped distribution. There was a significant interaction between the PSA level and GS (P-interaction<.001) such that only a PSA level2.5ng/mL significantly predicted poorer PCSM among patients with GS 8-10 disease. CONCLUSIONSAmong patients with high-grade disease, patients with PSA levels2.5ng/mL or PSA levels of 2.6 to 4ng/mL appear to have a higher risk for cancer-specific death in comparison with patients with PSA levels of 10.1 to 20ng/mL, and this supports the notion that low PSA levels in GS 8-10 disease may be a sign of aggressive and very poorly differentiated or anaplastic low PSA-producing tumors. Patients with low-PSA, GS 8-10 disease should be considered for clinical trials studying the use of chemotherapy and other novel agents for very high-risk prostate cancers. Cancer 2016;122:78-83. (c) 2015 American Cancer Society.