title: Detectable prostate-specific antigen Nadir during androgen-deprivation therapy predicts adverse prostate cancer-specific outcomes: results from the SEARCH database.
abstract: BACKGROUND
  A prostate-specific antigen (PSA) level <0.2 ng/ml 8 mo after starting on androgen-deprivation therapy (ADT) is correlated with better outcomes. However, not all men reach a nadir PSA level within 8 mo. Whether the lowest PSA on ADT-specifically, <0.2 ng/ml-can be used for risk stratification is untested.
  
  
  OBJECTIVE
  We examined the predictive value of small but detectable PSA nadir values on prostate cancer (PCa)-specific outcomes in men treated with early ADT after radical prostatectomy (RP).
  
  
  METHODS
  We performed a retrospective review of men treated with ADT after RP before metastases from the SEARCH database. We identified 402 men treated with ADT for elevated PSA following RP, of whom 294 men had complete data. Median follow-up after PSA nadir was 49 mo. All men had a PSA nadir <4 ng/ml; 223 men (76%) had an undetectable nadir.
  
  
  METHODS
  ADT for an elevated PSA following RP with no radiographic evidence of metastatic disease.
  
  
  METHODS
  PSA nadir on ADT was defined as the lowest PSA value during ADT. Proportional hazards models and the C index were used to test the association and predictive accuracy, respectively, between PSA nadir and PCa-specific outcomes.
  
  
  CONCLUSIONS
  Men with a PSA nadir between 0.01 and 0.2 ng/ml had a greater risk of progression to castration-resistant PCa (CRPC) (hazard ratio [HR]: 5.14; p<0.001), metastases (HR: 3.98; p=0.006), and PCa-specific mortality (PCSM) (HR: 5.33; p=0.003) than men with an undetectable nadir. When data were restricted to men followed with ultrasensitive PSA values (sensitivity of 0.01 ng/ml), the C index of PSA nadir alone for predicting CRPC, metastases, and PCSM was 0.88, 0.91, and 0.96, respectively.
  
  
  CONCLUSIONS
  A PSA nadir on ADT, even at a very low level, strongly predicts progression to CRPC, metastases, and PCSM. Men with a detectable PSA nadir during ADT should be considered for clinical trials.
authors.affiliation: Duke University School of Medicine, Durham, NC, USA; Veterans Affairs Medical Center, Durham, NC, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Keto
authors.affiliation: University of California at Los Angeles Medical Center, Los Angeles, CA, USA; Veterans Affairs Medical Center, Greater Los Angeles, Los Angeles, CA, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Aronson
authors.affiliation: Medical College of Georgia, Augusta, GA, USA; Veterans Affairs Medical Center, Augusta, GA, USA.
authors.forename: Martha K
authors.initials: MK
authors.lastname: Terris
authors.affiliation: Stanford University Medical Center, Palo Alto, CA, USA; Veterans Affairs Medical Center, Palo Alto, CA, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Presti
authors.affiliation: University of California at San Diego, San Diego, CA, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kane
authors.affiliation: Oregon Health and Science University, Portland, OR, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Amling
authors.affiliation: Duke University School of Medicine, Durham, NC, USA; Veterans Affairs Medical Center, Durham, NC, USA. Electronic address: steve.freedland@duke.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Freedland
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D000813:Anilides / Q000627:therapeutic use; D016208:Databases, Factual; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use; D009919:Orchiectomy; D011237:Predictive Value of Tests; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000628:therapy*; D012189:Retrospective Studies; D014105:Tosyl Compounds / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D014105:Tosyl Compounds; D007987:Gonadotropin-Releasing Hormone; C053541:bicalutamide; D017430:Prostate-Specific Antigen