title: Prospective evaluation of prostate cancer detected on biopsies 1, 2, 3 and 4: when should we stop?
abstract: OBJECTIVE
  We evaluated biochemical parameters and pathological features, as well as biopsy related morbidity of prostate cancer detected on biopsies 2, 3 and 4 in men with total serum prostate specific antigen (PSA) between 4 and 10 ng./ml. These features were compared to those detected on prostate biopsy 1.
  
  
  METHODS
  In this prospective European Prostate Cancer Detection study 1,051 men with total PSA between 4 and 10 ng./ml. underwent transrectal ultrasound guided sextant biopsy and 2 additional transition zone biopsies. All patients in whom biopsy samples were negative for prostate cancer underwent biopsy 2 after 6 weeks. If also negative, biopsies 3 and even 4 were performed at 8-week intervals. Those patients with clinically localized cancer underwent radical prostatectomy. Pathological and clinical features of patients diagnosed with cancer on either biopsy 1 or 2 and clinically organ confined disease who agreed to undergo radical prostatectomy were compared.
  
  
  RESULTS
  Cancer detection rates on biopsies 1, 2, 3 and 4 were 22% (231 of 1,051), 10% (83 of 820), 5% (36 of 737) and 4% (4 of 94), respectively. Overall, of the patients with clinically localized disease, which was 67% of cancers detected, 86% underwent radical prostatectomy and 14% opted for watchful waiting or radiation therapy. Overall, 58.0%, 60.9%, 86.3% and 100% of patients had organ confined disease on biopsies 1, 2, 3 and 4, respectively. Despite statistically significant differences in regard to multifocality (p = 0.009) and cancer location (p = 0.001), including cancer on biopsy 2 showing a lower rate of multifocality and a more apico-dorsal location, there were no differences in regard to stage (p = 0.2), Gleason score (p = 0.3), percent Gleason grade 4/5 (p = 0.2), serum PSA and patient age between biopsies 1 and 2. However, cancer detected on biopsies 3 and 4 had a significantly lower Gleason score (p = 0.001 and 0.001), lower rate of grade 4/5 (p = 0.02), and lower volume (p = 0.001 and 0.001) and stage (p = 0.001), respectively.
  
  
  CONCLUSIONS
  Despite differences in location and multifocality, pathological and biochemical features of cancer detected on biopsies 1 and 2 were similar, suggesting comparable biological behaviors. Cancer detected on biopsies 3 and 4 had a lower grade, stage and volume compared with that on biopsies 1 and 2. Morbidity on biopsies 1 and 2 was similar, whereas biopsies 3 and 4 had a slightly higher complication rate. Therefore, biopsy 2 in all cases of a negative finding on biopsy 1 appears justified. However, biopsies 3 and 4 should only be obtained in select patients with a high suspicion of cancer and/or poor prognostic factors on biopsy 1 or 2.
authors.affiliation: Department of Urology, University of Vienna, Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Djavan
authors.forename: V
authors.initials: V
authors.lastname: Ravery
authors.forename: A
authors.initials: A
authors.lastname: Zlotta
authors.forename: P
authors.initials: P
authors.lastname: Dobronski
authors.forename: M
authors.initials: M
authors.lastname: Dobrovits
authors.forename: M
authors.initials: M
authors.lastname: Fakhari
authors.forename: C
authors.initials: C
authors.lastname: Seitz
authors.forename: M
authors.initials: M
authors.lastname: Susani
authors.forename: A
authors.initials: A
authors.lastname: Borkowski
authors.forename: L
authors.initials: L
authors.lastname: Boccon-Gibod
authors.forename: C C
authors.initials: CC
authors.lastname: Schulman
authors.forename: M
authors.initials: M
authors.lastname: Marberger
mesh_terms: D000368:Aged; D001707:Biopsy, Needle; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010808:Physical Examination; D011237:Predictive Value of Tests; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000473:pathology*
chemical_list: D017430:Prostate-Specific Antigen