title: Margin details matter: The prognostic significance of pseudocapsule invasion at the site of involved margin in prostatectomy specimens.
abstract: BACKGROUND
  An involved surgical margin at prostatectomy has long been associated with elevated risk of prostate cancer recurrence; however, not all patients with an involved margin will relapse, and thus details of the involved margin may provide an opportunity for risk subset stratification. The present investigation seeks to determine whether a difference exists in recurrence rates when the margin involvement is at a site of prostate pseudocapsule invasion vs. within the prostate parenchyma proper.
  
  
  METHODS
  Patients were retrospectively identified for inclusion by clinically localized disease and prostate-specific antigen (PSA) level of< 30 ng/ml at diagnosis, managed with prostatectomy alone and identified to have involvement of surgical margin(s). Exclusion criteria were: pT3b or pN1 disease, immediate/nonsalvage postoperative radiation or hormone therapy, or insufficient follow-up (<12 mo). Pathology slides were reviewed by a pathologist blinded to outcome, for determination of pseudocapsule invasion at a site of margin involvement. Disease recurrence was defined as PSA level of ≥ 0.2 ng/ml and rising, per contemporary guidelines. Kaplan-Meier method was used for construction of disease control estimate confidence intervals; Cox Proportional Hazards Model was used to compare disease control across groups.
  
  
  RESULTS
  Between 2003 and 2010, 155 patients were identified for inclusion in the present study. The median age was 61 years, and all had clinical stage T1 and T2 disease (75% T1c). At diagnosis, the Gleason score was 6, 7, and 8-9 for 103 (66%), 42 (27%), and 10 (6%) patients, respectively, with median PSA level of 5.6 ng/ml (85%≤ 10). For 149 patients with reviewable margin site data, 51 (34%) demonstrated involvement within or beyond the pseudocapsule. At a median follow-up of 68 months (range: 13-137), 62 patients had experienced PSA relapse. The estimated 5-year PSA relapse rates for patients with an involved margin at the site of pseudocapsule invasion vs. prostate parenchyma were 49% vs. 34%, respectively (P = 0.017; hazard ratio = 1.853).
  
  
  CONCLUSIONS
  Early PSA relapse rates are high for patients with involved surgical margin(s) without seminal vesicle or node involvement at prostatectomy; however, for patients who are followed without immediate adjuvant therapy, presence of tumor cells at the margin in a site of pseudocapsule invasion or penetration confers a higher risk of recurrence.
authors.affiliation: Bismarck Cancer Center, Bismarck, ND.
authors.forename: James Kyle
authors.initials: JK
authors.lastname: Russo
authors.affiliation: Department of Pathology, St. Alexius Hospital, Bismarck, ND.
authors.forename: Michael
authors.initials: M
authors.lastname: Laszewski
authors.affiliation: Department of Pathology, Altru Health System, Grand Forks, ND.
authors.forename: Mark
authors.initials: M
authors.lastname: Rodacker
authors.affiliation: Department of Pediatrics, University of Iowa Carver School of Medicine, Iowa City, IA.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Watkins
authors.affiliation: Bismarck Cancer Center, Bismarck, ND.
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Dufan
authors.affiliation: Department of Urology, Sanford Bismarck Medical Center, Bismarck, ND.
authors.forename: Nadim
authors.initials: N
authors.lastname: Koleilat
authors.affiliation: Department of Radiation Oncology, University of Iowa Carver School of Medicine, Iowa City, IA. Electronic address: john.m.watkins.md@hotmail.com.
authors.forename: John M
authors.initials: JM
authors.lastname: Watkins
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000601:surgery*
chemical_list: D017430:Prostate-Specific Antigen
keywords: Prostate neoplasms; Radiation therapy; Radical prostatectomy; Surgical pathology