title: Impact of stage migration and practice changes on high-risk prostate cancer: results from patients treated with radical prostatectomy over the last two decades.
abstract: OBJECTIVE
  To evaluate the impact of year of surgery on clinical, pathological and oncological outcomes of patients with high-risk prostate cancer.
  
  
  METHODS
  We evaluated 1 033 patients with clinically high-risk prostate cancer, defined as the presence of at least one of the following risk factors: preoperative prostate-specific antigen (PSA) level >20 ng/mL, and/or clinical stage ≥T3, and/or biopsy Gleason score ≥8. Patients were treated between 1990 and 2013 at a single institution. The year-by-year trends in clinical and pathological characteristics were examined. Multivariable Cox regression analysis was used to test the relationship between year of surgery and oncological outcomes.
  
  
  RESULTS
  We observed a decrease over time in the proportion of patients with high-risk disease (preoperative PSA >20 ng/mL or clinical stage cT3). A trend in the opposite direction was seen for biopsy Gleason score ≥8 tumours. We observed a considerable increase in the median number of lymph nodes removed, which was associated with an increased rate of lymph node invasion (LNI). On multivariable Cox regression analysis, year of surgery was associated with a reduced risk of biochemical recurrence (hazard ratio [HR] per 5-year interval 0.90, 95% confidence interval [CI] 0.84-0.96; P = 0.01) and distant metastasis (HR per 5-year interval 0.91, 95% CI 0.83-0.99; P = 0.039), after adjusting for age, preoperative PSA, pathological stage, LNI, surgical margin status, and pathological Gleason score.
  
  
  CONCLUSIONS
  In this single-centre study, an increased diagnosis of localized and less extensive high-grade prostate cancer was observed over the last two decades. Patients with high-risk disease who were selected for radical prostatectomy showed better cancer control over time. Better definitions of what constitutes high-risk prostate cancer among contemporary patients are needed.
authors: Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.|Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: Nicola
authors: N
authors: Fossati
authors: Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.|Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors: Niccolò M
authors: NM
authors: Passoni
authors: Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors: Marco
authors: M
authors: Moschini
authors: Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors: Giorgio
authors: G
authors: Gandaglia
authors: Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors: Alessandro
authors: A
authors: Larcher
authors: Department of Pathology, IRCCS Ospedale San Raffaele, Milan, Italy.
authors: Massimo
authors: M
authors: Freschi
authors: Department of Urology, Humanitas Clinical and Research Centre, Humanitas University, Milan, Italy.
authors: Giorgio
authors: G
authors: Guazzoni
authors: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: Daniel D
authors: DD
authors: Sjoberg
authors: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: Andrew J
authors: AJ
authors: Vickers
authors: Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors: Francesco
authors: F
authors: Montorsi
authors: Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors: Alberto
authors: A
authors: Briganti
mesh_terms: D000368:Aged; D001706:Biopsy; D006801:Humans; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000601:surgery*; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors
chemical_list: D017430:Prostate-Specific Antigen
keywords: cancer recurrence; high risk; prostate cancer; radical prostatectomy; stage migration