title: Familial prostate cancer: a different disease?
abstract: OBJECTIVE
  We analyzed the outcome after radical prostatectomy of patients with familial prostate cancer versus patients with sporadic prostate cancer.
  
  
  METHODS
  The study included 720 patients with prostate carcinoma who were treated with prostatectomy between 1987 and 1996. Patients were excluded from the study if they had received adjuvant or neoadjuvant treatment, or had no available pretreatment prostatic specific antigen (PSA) level, no available biopsy Gleason score, incomplete pathological information or no available followup PSA levels. The analysis was performed on 529 cases. Patients were considered to have a positive family history for prostate cancer when the index patient confirmed the diagnosis of prostate cancer in a first degree relative (brother or father). The outcomes of interest were biochemical relapse-free survival, local failure and distant metastases. Proportional hazards were used to analyze the effect of family history and confounding variables (that is age, stage, biopsy Gleason score, initial PSA levels, surgical specimen Gleason score, extracapsular extension, lymph node metastasis, seminal vesicle invasion and surgical margin involvement) on treatment outcome.
  
  
  RESULTS
  Median followup was 30 months. Of all cases 12% had a positive family history. Younger age was the only factor associated with positive family history, with 18% of patients younger than 65 years having a positive family history versus 6% of older patients (chi-square p <0.001). The 5-year biochemical relapse-free survival rate for the entire group was 64%. The 5-year biochemical relapse-free survival rates for patients with negative family history versus positive history were 66% and 46%, respectively (p = 0.001). A multivariate time-to-failure analysis using the proportional hazards model was performed based on family history, age (less than 65 versus 65 to 69 versus 70 or greater, initial PSA (10 or less versus greater than 10), biopsy Gleason score (6 or less versus 7 or greater), clinical T stage (T1-T2A versus T2B-C), prostatectomy specimen Gleason score (6 or less versus 7 or greater), extracapsular extension, seminal vesicle involvement, surgical margin involvement and lymph node involvement. After adjusting for the potential confounding factors, positive family history remained strongly associated with biochemical failure. The clinical failure rate for the entire group was 14%. The 5-year local failure rate was 7%, with positive surgical margins being the only independent predictor of local failure. The 5-year distant metastasis rate was 8%, with family history and initial PSA levels being independent predictors of distant relapse.
  
  
  CONCLUSIONS
  Our study suggests that patients with a familial prostate cancer have a higher likelihood of biochemical failure after radical prostatectomy than patients with sporadic cancer. This effect is independent of pretreatment or pathological factors. Our results suggest that the higher failure rates associated with familial prostate cancer are mainly secondary to higher distant relapse rates, and that familial prostate cancer may be more biologically aggressive than sporadic cancers.
authors.affiliation: Department of Radiation Oncology, Cleveland Clinic Foundation, Case Western Reserve University, Ohio 44195, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Kupelian
authors.forename: E A
authors.initials: EA
authors.lastname: Klein
authors.forename: J S
authors.initials: JS
authors.lastname: Witte
authors.forename: V A
authors.initials: VA
authors.lastname: Kupelian
authors.forename: J H
authors.initials: JH
authors.lastname: Suh
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D000368:Aged; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D015996:Survival Rate