title: Secondary therapy, metastatic progression, and cancer-specific mortality in men with clinically high-risk prostate cancer treated with radical prostatectomy.
abstract: OBJECTIVE
  Commonly used definitions for high-risk prostate cancer identify men at increased risk of PSA relapse after radical prostatectomy (RP). We assessed how accurately these definitions identify patients likely to receive secondary cancer therapy, experience metastatic progression, or die of prostate cancer.
  
  
  METHODS
  Among 5960 men with clinically localized or locally advanced prostate cancer who underwent RP, we identified eight different high-risk subsets, each comprising 4-40% of the study population. Estimates of freedom from radiation therapy, hormonal therapy, and metastatic progression after surgery were generated for each high-risk cohort with the Kaplan-Meier method, and hazard ratios (HR) were calculated with a Cox proportional hazards regression. The cumulative incidence and HR for prostate cancer-specific mortality (PCSM) were estimated with competing risk analysis.
  
  
  RESULTS
  Each of the studied high-risk criteria was associated with increased hazard of secondary cancer therapy (HR=1.3-5.2, p<0.05) and metastatic progression (HR=2.1-6.9, p<0.05). However, depending on the definition, the probability of freedom from additional therapy 10 yr after surgery ranged from 35% to 76%. The 10-yr cumulative incidence of PCSM in high-risk patients ranged from 3% to 11% (HR=3.2-10.4, p<0.0005).
  
  
  CONCLUSIONS
  Commonly used definitions for high-risk prostate cancer identify men at increased risk of secondary cancer therapy, metastatic progression, and PCSM following RP. However, a substantial proportion of high-risk patients remain free from additional therapy or metastatic disease many years after surgery. The risk of PCSM within 10 yr of treatment is remarkably low, even for patients at the highest risk of recurrent disease.
authors.affiliation: Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Ofer
authors.initials: O
authors.lastname: Yossepowitch
authors.forename: Scott E
authors.initials: SE
authors.lastname: Eggener
authors.forename: Angel M
authors.initials: AM
authors.lastname: Serio
authors.forename: Brett S
authors.initials: BS
authors.lastname: Carver
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Bianco
authors.forename: Peter T
authors.initials: PT
authors.lastname: Scardino
authors.forename: James A
authors.initials: JA
authors.lastname: Eastham
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000628:therapy; D009367:Neoplasm Staging; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy; D018714:Radiotherapy, Adjuvant / Q000379:methods; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D000970:Antineoplastic Agents