title: Importance and outcome relevance of central pathology review in prostatectomy specimens: data from the SAKK 09/10 randomized trial on prostate cancer.
abstract: To conduct a central pathology review within a randomized clinical trial on salvage radiation therapy (RT) in the presence of biochemical recurrence after prostatectomy to assess whether this results in changes in histopathological prognostic factors, such as Gleason score.
  
  
  
  A total of 350 patients were randomized and specimens from 279 patients (80%) were centrally reviewed by a dedicated genitourinary pathologist. Gleason score, tumour classification and resection margin status were reassessed and compared with the results of local pathology review. Agreement was assessed using contingency tables and Cohen's kappa coefficient. The association between other histopathological features (e.g. largest diameter of carcinoma) and rapid biochemical progression (up to 6 months after salvage RT) was also investigated.
  
  
  
  There was good concordance between central and local pathology review for seminal vesicle invasion (pT3b: 91%; κ = 0.95 [95% confidence interval {CI} 0.89, 1.00]), extraprostatic extension (pT3a/b: 94%; κ = 0.82 [95% CI 0.75, 0.89]) and positive surgical margin (PSM) status (87%; κ = 0.7 [95% CI 0.62, 0.79]). The rate of agreement was lower for Gleason score (78%; κ = 0.61 [95% CI 0.52, 0.70]). The median (range) largest diameter of carcinoma was 16 (3-38) mm. A total of 49 patients (18%) experienced rapid biochemical progression after salvage RT. Largest diameter of carcinoma (odds ratio [OR] 2.04 [95% CI 1.30, 3.20]; P = 0.002), resection margin status (OR 0.36 [95% CI 0.18, 0.72]; P = 0.004) and Gleason score (OR 1.55 [95% CI 1.00, 2.42]; P = 0.05) remained associated with rapid progression after salvage RT after backward selection.
  
  
  
  The results of the central pathology analyses showed concordance between central and local pathology review with regard to seminal vesicle invasion, extraprostatic extension and PSM status, but a lower rate of agreement for Gleason score. Largest diameter of carcinoma was found to be a potential prognostic factor for rapid biochemical progression after salvage RT.
authors.affiliation: Department of Radiation Oncology, Inselspital, Bern University Hospital, Bern, Switzerland.
authors.forename: Pirus
authors.initials: P
authors.lastname: Ghadjar
authors.affiliation: SAKK Coordinating Center, Bern, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hayoz
authors.affiliation: Department of Pathology of the University of Bern, Bern, Switzerland.
authors.forename: Vera
authors.initials: V
authors.lastname: Genitsch
authors.affiliation: Department of Radiation Oncology, Kantonsspital Graubünden, Chur, Switzerland.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Zwahlen
authors.affiliation: University Hospital Dresden, Dresden, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hölscher
authors.affiliation: Kantonsspital Luzern, Luzern, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Gut
authors.affiliation: University Hospital Würzburg, Würzburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Guckenberger
authors.affiliation: University Hospital Rostock, Rostock, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Hildebrandt
authors.affiliation: University Hospital Tübingen, Tübingen, Germany.
authors.forename: Arndt-Christian
authors.initials: AC
authors.lastname: Müller
authors.affiliation: Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Putora
authors.affiliation: University Hospital Basel, Basel, Switzerland.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Papachristofilou
authors.affiliation: SAKK Coordinating Center, Bern, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Stalder
authors.affiliation: SAKK Coordinating Center, Bern, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Biaggi-Rudolf
authors.affiliation: Hirslanden Hospital Group, Zürich, Switzerland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Sumila
authors.affiliation: Stadtspital Triemli, Zürich, Switzerland.
authors.forename: Helmut
authors.initials: H
authors.lastname: Kranzbühler
authors.affiliation: University Hospital Zürich, Zürich, Switzerland.
authors.forename: Yousef
authors.initials: Y
authors.lastname: Najafi
authors.affiliation: Ghent University Hospital, Ghent, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Ost
authors.affiliation: Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland.
authors.forename: Ngwa C
authors.initials: NC
authors.lastname: Azinwi
authors.affiliation: Kantonsspital Münsterlingen, Münsterlingen, Switzerland.
authors.forename: Christiane
authors.initials: C
authors.lastname: Reuter
authors.affiliation: Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Bodis
authors.affiliation: Hôpital Valais, Sion, Switzerland.
authors.forename: Kaouthar
authors.initials: K
authors.lastname: Khanfir
authors.affiliation: Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Budach
authors.affiliation: Department of Radiation Oncology, Inselspital, Bern University Hospital, Bern, Switzerland.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Aebersold
authors.affiliation: Department of Urology, Inselspital, Bern University Hospital, Bern, Switzerland.
authors.forename: George N
authors.initials: GN
authors.lastname: Thalmann
mesh_terms: D000368:Aged; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000473:pathology*; D018714:Radiotherapy, Adjuvant; D011897:Random Allocation; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016879:Salvage Therapy; D016896:Treatment Outcome
chemical_list: D017430:Prostate-Specific Antigen
keywords: #PCSM; #ProstateCancer; central pathology review; radiation; salvage