title: Association of Radical Local Treatment with Mortality in Men with Very High-risk Prostate Cancer: A Semiecologic, Nationwide, Population-based Study.
abstract: Current guidelines recommend androgen deprivation therapy only for men with very high-risk prostate cancer (PCa), but there is little evidence to support this stance.
  
  
  
  To investigate the association between radical local treatment and mortality in men with very high-risk PCa.
  
  
  
  Semiecologic study of men aged <80 yr within the Prostate Cancer data Base Sweden, diagnosed in 1998-2012 with very high-risk PCa (local clinical stage T4 and/or prostate-specific antigen [PSA] level 50-200ng/ml, any N, and M0). Men with locally advanced PCa (local clinical stage T3 and PSA level <50ng/ml, any N, and M0) were used as positive controls.
  
  
  
  Proportion of men who received prostatectomy or full-dose radiotherapy in 640 experimental units defined by county, diagnostic period, and age at diagnosis.
  
  
  
  PCa and all-cause mortality rate ratios (MRRs).
  
  
  
  Both PCa and all-cause mortality were half as high in units in the highest tertile of exposure to radical local treatment compared with units in the lowest tertile (PCa MRR: 0.51; 95% confidence interval [CI], 0.28-0.95; and all-cause MRR: 0.56; 95% CI, 0.33-0.92). The results observed for locally advanced PCa for highest versus lowest tertile of exposure were in agreement with results from randomized trials (PCa MRR: 0.75; 95% CI, 0.60-0.94; and all-cause MRR: 0.85; 95% CI, 0.72-1.00). Although the semiecologic design minimized selection bias on an individual level, the effect of high therapeutic activity could not be separated from that of high diagnostic activity.
  
  
  
  The substantially lower mortality in units with the highest exposure to radical local treatment suggests that radical treatment decreases mortality even in men with very high-risk PCa for whom such treatment has been considered ineffective.
  
  
  
  Men with very high-risk prostate cancer diagnosed and treated in units with the highest exposure to surgery or radiotherapy had a substantially lower mortality.
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umeå, Sweden. Electronic address: par.stattin@umu.se.
authors.forename: Pär
authors.initials: P
authors.lastname: Stattin
authors.affiliation: Regional Cancer Centre Uppsala Örebro, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Sandin
authors.affiliation: Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Frederik Birkebæk
authors.initials: FB
authors.lastname: Thomsen
authors.affiliation: Regional Cancer Centre Uppsala Örebro, Uppsala University Hospital, Uppsala, Sweden; King's College London, School of Medicine, Division of Cancer Studies, Cancer Epidemiology Group, London, UK.
authors.forename: Hans
authors.initials: H
authors.lastname: Garmo
authors.affiliation: Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umeå, Sweden; Department of Urology, Ryhov Hospital, Jönköping, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Robinson
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ingela Franck
authors.initials: IF
authors.lastname: Lissbrant
authors.affiliation: Department of Radiation Sciences, Umeå University, Umeå, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Jonsson
authors.affiliation: Department of Translational Medicine, Division of Urological Cancer, Lund University, Lund, Sweden; CamPARI Clinic, Department of Urology, Cambridge University Hospitals, Cambridge, UK.
authors.forename: Ola
authors.initials: O
authors.lastname: Bratt
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D016208:Databases, Factual; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy / Q000009:adverse effects / Q000401:mortality*; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D011878:Radiotherapy / Q000401:mortality; D011879:Radiotherapy Dosage; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Nationwide; PCBaSe; Population-based; Prostate cancer; Radical; Semiecologic; Treatment; Very high-risk