title: Development and multi-institutional validation of an upgrading risk tool for Gleason 6 prostate cancer.
abstract: BACKGROUND
  Many patients with low-risk prostate cancer (PC) who are diagnosed with Gleason score 6 at biopsy are ultimately found to harbor higher grade PC (Gleason ≥ 7) at radical prostatectomy. This finding increases risk of recurrence and cancer-specific mortality. Validated clinical tools that are available preoperatively are needed to improve the ability to recognize likelihood of upgrading in patients with low-risk PC.
  
  
  METHODS
  More than 30 clinicopathologic parameters were assessed in consecutive patients with Gleason 6 PC upon biopsy who underwent radical prostatectomy. A nomogram for predicting upgrading (Gleason ≥ 7) on final pathology was generated using multivariable logistic regression in a development cohort of 431 patients. External validation was performed in 2 separate cohorts consisting of 1151 patients and 392 patients. Nomogram performance was assessed using receiver operating characteristic curves, calibration, and decision analysis.
  
  
  RESULTS
  On multivariable analysis, variables predicting upgrading were prostate-specific antigen density using ultrasound (odds ratio [OR] = 229, P = .003), obesity (OR = 1.90, P = .05), number of positive cores (OR = 1.23, P = .01), and maximum core involvement (OR = 0.02, P = .01). On internal validation, the bootstrap-corrected predictive accuracy was 0.753. External validation revealed a predictive accuracy of 0.677 and 0.672. The nomogram demonstrated excellent calibration in all 3 cohorts and decision curves demonstrated high net benefit across a wide range of threshold probabilities. The nomogram demonstrated areas under the curve of 0.597 to 0.672 for predicting upgrading in subsets of men with very low-risk PC who meet active surveillance criteria (all P < .001), allowing further risk stratification of these individuals.
  
  
  CONCLUSIONS
  A nomogram was developed and externally validated that uses preoperative clinical parameters and biopsy findings to predict the risk of pathological upgrading in Gleason 6 patients. This can be used to further inform patients with lower risk PC who are considering treatment or active surveillance.
authors.affiliation: Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Matthew
authors.initials: M
authors.lastname: Truong
authors.forename: Jon A
authors.initials: JA
authors.lastname: Slezak
authors.forename: Chee Paul
authors.initials: CP
authors.lastname: Lin
authors.forename: Viacheslav
authors.initials: V
authors.lastname: Iremashvili
authors.forename: Martins
authors.initials: M
authors.lastname: Sado
authors.forename: Aria A
authors.initials: AA
authors.lastname: Razmaria
authors.forename: Glen
authors.initials: G
authors.lastname: Leverson
authors.forename: Mark S
authors.initials: MS
authors.lastname: Soloway
authors.forename: Scott E
authors.initials: SE
authors.lastname: Eggener
authors.forename: E Jason
authors.initials: EJ
authors.lastname: Abel
authors.forename: Tracy M
authors.initials: TM
authors.lastname: Downs
authors.forename: David F
authors.initials: DF
authors.lastname: Jarrard
mesh_terms: D000465:Algorithms; D001706:Biopsy / Q000379:methods; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D011336:Probability; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology* / Q000601:surgery; D015203:Reproducibility of Results
chemical_list: C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: active surveillance; low-risk prostate cancer; prostate-specific antigen