title: Tumor volume in insignificant prostate cancer: increasing threshold gains increasing risk.
abstract: BACKGROUND
  An increased tumor volume threshold (<2.5 ml) is suggested to define insignificant prostate cancer (iPCa). We hypothesize that an increasing tumor volume within iPCa patients increases the risk of biochemical recurrence (BCR) after radical prostatectomy (RP).
  
  
  METHODS
  We relied on RP patients treated between 1992 and 2008. Multivariable Cox regression analyses predicting BCR within patients harboring favorable pathological characteristics (≤pT2, pN0/Nx, Gleason 3 + 3). Kaplan-Meier analysis was performed for BCR-free survival within iPCa patients (≤pT2, pN0/Nx, Gleason 3 + 3, tumor volume: <0.5 vs. 0.5-2.49 ml).
  
  
  RESULTS
  From 1,829 patients, 141 (7.7%) and 310 (16.9%) harbored iPCa (tumor volume: <0.5 vs. 0.5-2.49 ml), respectively. Of those, 21 (14.9%) versus 31 (10.0%) had PSA >10 ng/ml. Tumor volume achieved independent predictor status for BCR. Specifically, iPCa patients with increasing tumor volume (0.5-2.49 ml) were at higher risk of BCR after RP than those with tumor volume <0.5 ml (HR: 8.8, 95% CI: 1.2-65.9, P = 0.04). Kaplan-Meier analysis recorded superior BCR-free survival in iPCa patients with lower tumor volume (<0.5 ml) (log-rank P = 0.009). The 10-year cancer-specific death rate was 0 versus 0.5%.
  
  
  CONCLUSIONS
  Contemporary iPCa definition incorporates intermediate and high-risk patients (PSA: 10-20 and >20 ng/ml). Despite most favorable pathological characteristics, iPCa patients are not devoid of BCR after RP. Moreover, iPCa patients were at higher risk of BCR, when increasing tumor volume up to 2.49 ml was at play. Taken together the contemporary concept of iPCa is suboptimal. Especially, an increased tumor volume threshold for defining iPCa cannot be recommended according to our data. Clinicians might take these considerations into account during decision-making process.
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Schiffmann
authors.forename: Judith
authors.initials: J
authors.lastname: Connan
authors.forename: Georg
authors.initials: G
authors.lastname: Salomon
authors.forename: Katharina
authors.initials: K
authors.lastname: Boehm
authors.forename: Burkhard
authors.initials: B
authors.lastname: Beyer
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.forename: Pierre
authors.initials: P
authors.lastname: Tennstedt
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.forename: Hartwig
authors.initials: H
authors.lastname: Huland
mesh_terms: D000368:Aged; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D011379:Prognosis; D011467:Prostate / Q000473:pathology*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D012044:Regression Analysis; D012306:Risk; D016019:Survival Analysis; D047368:Tumor Burden
keywords: biochemical recurrence; insignificant prostate cancer; radical prostatectomy; tumor volume