title: Association of very low prostate-specific antigen levels with increased cancer-specific death in men with high-grade prostate cancer.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  The 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 > 40 ng/mL) and GS (8-10 vs ≤ 7).
  
  
  RESULTS
  The median follow-up was 38 months. Among men with GS 8-10 disease, with a PSA level of 4.1 to 10 ng/mL as the referent, the adjusted hazard ratio for PCSM for men was 2.15 with a PSA level ≤ 2.5 ng/mL (95% confidence interval [CI], 1.65-2.79; P < .001), 1.60 with a PSA level of 2.6 to 4 ng/mL (95% CI, 1.22-2.10; P = .001), 1.60 with a PSA level of 10.1 to 20 ng/mL (95% CI, 1.41-1.82; P < .001), 2.08 with a PSA level of 20.1 to 40 ng/mL (95% CI, 1.81-2.38; P < .001), and 3.23 with a PSA level > 40 ng/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 level ≤ 2.5 ng/mL significantly predicted poorer PCSM among patients with GS 8-10 disease.
  
  
  CONCLUSIONS
  Among patients with high-grade disease, patients with PSA levels ≤ 2.5 ng/mL or PSA levels of 2.6 to 4 ng/mL appear to have a higher risk for cancer-specific death in comparison with patients with PSA levels of 10.1 to 20 ng/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.
authors.affiliation: Department of Internal Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Brandon A
authors.initials: BA
authors.lastname: Mahal
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Ayal A
authors.initials: AA
authors.lastname: Aizer
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Efstathiou
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Nguyen
mesh_terms: D000368:Aged; D015331:Cohort Studies; D018450:Disease Progression; D006801:Humans; D007610:Kallikreins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D012044:Regression Analysis; D012307:Risk Factors; D018426:SEER Program; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Gleason score; aggressive disease; cancer outcome; prostate-specific antigen; prostatic neoplasm