title: Local Therapy Improves Survival in Metastatic Prostate Cancer.
abstract: Treatment of the primary, termed local therapy (LT), may improve survival in metastatic prostate cancer (mPCa) versus no local therapy (NLT).
  
  
  
  To assess cancer-specific mortality (CSM) after LT versus NLT in mPCa.
  
  
  
  Within the Surveillance, Epidemiology and End Results database (2004-2013), 13 692 mPCa patients were treated with LT (radical prostatectomy [RP] or radiation therapy [RT]) or NLT.
  
  
  
  Multivariable competing risk regression analyses (MVA CRR) tested CSM after propensity score matching (PSM) in two analyses, (1) NLT versus LT and (2) RP versus RT, and were complemented with interaction, sensitivity, unmeasured confounder, and landmark analyses.
  
  
  
  Of 13 692 mPCa patients, 474 received LT: 313 underwent RP and 161 RT. In MVA CRR, after PSM, LT (n=474) results in lower CSM (subhazard ratio [SHR] 0.40, 95% confidence interval [CI] 0.32-0.50) versus NLT (n=1896). In MVA CRR after PSM, RP (n=161) results in lower CSM (SHR 0.59, 95% CI 0.35-0.99) versus RT (n=161). Invariably, lowest CSM rates were recorded for Gleason ≤7, ≤cT3, and M1a substage. Interaction and sensitivity analyses confirmed the robustness of results, and landmark analyses rejected the bias favouring LT. A strong unmeasured confounder (HR=5), affecting 30% of NLT patients, could obliterate LT benefit. Data were retrospective.
  
  
  
  In mPCa, LT results in lower mortality relative to NLT. Within LT, lower mortality is recorded after RP than RT. Patients with most favourable grade, local stage, and metastatic substage derive most benefit from LT. They also derive most benefit from RP, when LT types are compared (RP vs RT). It is important to consider study limitations until ongoing clinical trials confirm the proposed benefits.
  
  
  
  Individuals with prostate cancer that spreads outside of the prostate might still benefit from prostate-directed treatments, such as radiation or surgery, in addition to receiving androgen deprivation therapy.
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada; Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: S.Bannurah@googlemail.com.
authors.forename: Sami-Ramzi
authors.initials: SR
authors.lastname: Leyh-Bannurah
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada; Department of Urology, University of Montreal Health Center, Montreal, Canada.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Gazdovich
authors.affiliation: Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Budäus
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada; Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Zaffuto
authors.affiliation: Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.affiliation: Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vattikuti Urology Institute and VUI Center for Outcomes Research Analytics and Evaluation (VCORE), Henry Ford Hospital, Henry Ford Health System, Detroit, MI, USA.
authors.forename: Firas
authors.initials: F
authors.lastname: Abdollah
authors.affiliation: Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.affiliation: Department of Urology, Academic Hospital Braunschweig, Braunschweig, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Schiffmann
authors.affiliation: Vattikuti Urology Institute and VUI Center for Outcomes Research Analytics and Evaluation (VCORE), Henry Ford Hospital, Henry Ford Health System, Detroit, MI, USA.
authors.forename: Mani
authors.initials: M
authors.lastname: Menon
authors.affiliation: Department of Urology Medical University of Vienna, Vienna, Austria.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Margit
authors.initials: M
authors.lastname: Fisch
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Chun
authors.affiliation: Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Steuber
authors.affiliation: Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Huland
authors.affiliation: Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada; Department of Urology, University of Montreal Health Center, Montreal, Canada.
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D057216:Propensity Score; D016016:Proportional Hazards Models; D011468:Prostatectomy / Q000009:adverse effects / Q000401:mortality; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D012307:Risk Factors; D018426:SEER Program; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
keywords: Brachytherapy; Cytoreductive prostatectomy; Local radiotherapy; Radical prostatectomy; Standard of care