title: Outcomes of men with an elevated prostate-specific antigen (PSA) level as their sole preoperative intermediate- or high-risk feature.
abstract: OBJECTIVE
  To investigate the post-prostatectomy and long-term outcomes of men presenting with an elevated pretreatment prostate-specific antigen (PSA) level (>10 ng/mL), but otherwise low-risk features (biopsy Gleason score ≤6 and clinical stage ≤T2a).
  
  
  METHODS
  PSA-incongruent intermediate-risk (PII) cases were defined as those patients with preoperative PSA >10 and ≤20 ng/mL but otherwise low-risk features, and PSA-incongruent high-risk (PIH) cases were defined as men with PSA >20 ng/mL but otherwise low-risk features. Our institutional radical prostatectomy database (1992-2012) was queried and the results were stratified into D'Amico low-, intermediate- and high risk, PSA-incongruent intermediate-risk and PSA-incongruent high-risk cases. Prostate cancer (PCa) features and outcomes were evaluated using appropriate comparative tests. Multivariable analyses were adjusted for age, race and year of surgery.
  
  
  RESULTS
  Of the total cohort of 17 608 men, 1132 (6.4%) had PII-risk disease and 183 (1.0%) had PIH-risk disease. Compared with the low-risk group, the odds of upgrading at radical prostatectomy (RP) were 2.20 (95% CI 1.93-2.52; P < 0.001) for the PII group and 3.58 (95% CI 2.64-4.85; P < 0.001) for the PIH group, the odds of extraprostatic disease at RP were 2.35 (95% CI 2.05-2.68; P < 0.001) for the PII group and 6.68 (95% CI 4.89-9.15; P < 0.001) for the PIH group, and the odds of positive surgical margins were 1.97 (95% CI 1.67-2.33; P < 0.001) for the PII group and 3.54 (95% CI 2.50-4.95, P < 0.001) for the PIH group. Compared with low-risk disease, PII-risk disease was associated with a 2.85-, 2.99- and 3.32-fold greater risk of biochemical recurrence (BCR), metastasis and PCa-specific mortality, respectively, and PIH-risk disease was associated with a 5.32-, 6.14- and 7.07-fold greater risk of BCR, metastasis and PCa-specific mortality, respectively (P ≤ 0.001 for all comparisons). For the PII group, the higher risks of positive surgical margins, upgrading, upstaging and BCR were dependent on PSA density (PSAD): men in the PII group who had a PSAD <0.15 ng/mL/g were not at higher risk compared with those in the low-risk group. Men in the PII group with a PSAD ≥0.15 ng/mL/g and men in the PIH group were more likely to have an anterior component of the dominant tumour (59 and 64%, respectively) compared with those in the low- (35%) and intermediate-risk group (39%) and those in the PII-risk group with PSAD <0.15 ng/mL/g (29%).
  
  
  CONCLUSIONS
  Men with PSA >20 ng/mL or men with PSA >10 and ≤20 ng/mL with a PSAD ≥0.15 ng/mL/g, but otherwise low-risk PCa, are at greater risk of adverse pathological and oncological outcomes and may be inappropriate candidates for active surveillance. These men are at greater risk of having anterior tumours that are undersampled at biopsy, so if treatment is deferred, ancillary testing such as anterior zone sampling or magnetic resonance imaging should be strongly encouraged. Men with elevated PSA levels >10 and ≤20 ng/mL but low PSAD have outcomes similar to those in the low-risk group, and consideration of surveillance is appropriate in these cases.
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Farzana A
authors.initials: FA
authors.lastname: Faisal
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Debasish
authors.initials: D
authors.lastname: Sundi
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Phillip M
authors.initials: PM
authors.lastname: Pierorazio
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Ball
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Humphreys
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Misop
authors.initials: M
authors.lastname: Han
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: H Ballentine
authors.initials: HB
authors.lastname: Carter
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Trinity J
authors.initials: TJ
authors.lastname: Bivalacqua
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schaeffer
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Ross
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000401:mortality; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D017430:Prostate-Specific Antigen
keywords: outcome; prostate cancer; prostate-specific antigen; prostatectomy; risk
references.citation: BJU Int. 2011 Mar;107(5):765-770
references.pmid: 20875089
references.citation: Urology. 2007 Nov;70(5):931-5
references.pmid: 18068450
references.citation: J Surg Oncol. 2014 Jun;109(8):830-5
references.pmid: 24610744
references.citation: Int Urol Nephrol. 2013 Oct;45(5):1257-62
references.pmid: 23864415
references.citation: J Urol. 2014 Jan;191(1):60-7
references.pmid: 23770146
references.citation: Urology. 2000 Aug 1;56(2):273-7
references.pmid: 10925093
references.citation: J Urol. 2003 Apr;169(4):1320-4
references.pmid: 12629352
references.citation: J Urol. 2000 Apr;163(4):1155-60
references.pmid: 10737486
references.citation: BJU Int. 2006 Dec;98(6):1167-71
references.pmid: 17026586
references.citation: BJU Int. 2012 Apr;109(7):988-93
references.pmid: 21880104
references.citation: JAMA. 1999 Apr 21;281(15):1395-400
references.pmid: 10217055
references.citation: BJU Int. 2010 May;105(9):1231-6
references.pmid: 19817743
references.citation: Cancer. 1993 Jun 1;71(11):3582-93
references.pmid: 7683970
references.citation: Cancer. 2007 Jun 15;109(12):2432-8
references.pmid: 17497649
references.citation: Clin Radiol. 2008 Aug;63(8):871-9
references.pmid: 18625351
references.citation: J Urol. 2013 Dec;190(6):2033-8
references.pmid: 23680308
references.citation: Int J Clin Exp Pathol. 2012;5(6):496-502
references.pmid: 22949931
references.citation: JAMA. 1998 Sep 16;280(11):969-74
references.pmid: 9749478
references.citation: J Clin Oncol. 2011 Jun 1;29(16):2185-90
references.pmid: 21464416
references.citation: Int J Radiat Oncol Biol Phys. 1999 Nov 1;45(4):841-6
references.pmid: 10571187
references.citation: Cancer. 2007 Jul 1;110(1):56-61
references.pmid: 17530618
references.citation: J Urol. 2013 Sep;190(3):867-73
references.pmid: 23542406
references.citation: JAMA. 1994 Feb 2;271(5):368-74
references.pmid: 7506797