title: Clinical Outcomes for Patients with Gleason Score 9-10 Prostate Adenocarcinoma Treated With Radiotherapy or Radical Prostatectomy: A Multi-institutional Comparative Analysis.
abstract: The long natural history of prostate cancer (CaP) limits comparisons of efficacy between radical prostatectomy (RP) and external beam radiotherapy (EBRT), since patients treated years ago received treatments considered suboptimal by modern standards (particularly with regards to androgen deprivation therapy [ADT] and radiotherapy dose-escalation]. Gleason score (GS) 9-10 CaP is particularly aggressive, and clinically-relevant endpoints occur early, facilitating meaningful comparisons.
  
  
  
  To compare outcomes of patients with GS 9-10 CaP following EBRT, extremely-dose escalated radiotherapy (as exemplified by EBRT+brachytherapy [EBRT+BT]), and RP.
  
  
  
  Retrospective analysis of 487 patients with biopsy GS 9-10 CaP treated between 2000 and 2013 (230 with EBRT, 87 with EBRT+BT, and 170 with RP). Most radiotherapy patients received ADT and dose-escalated radiotherapy.
  
  
  
  Kaplan-Meier analysis and multivariate Cox regression estimated and compared 5-yr and 10-yr rates of distant metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS).
  
  
  
  The median follow-up was 4.6 yr. Local salvage and systemic salvage were performed more frequently in RP patients (49.0% and 30.1%) when compared with either EBRT patients (0.9% and 19.7%) or EBRT+BT patients (1.2% and 16.1%, p<0.0001). Five-yr and 10-yr distant metastasis-free survival rates were significantly higher with EBRT+BT (94.6% and 89.8%) than with EBRT (78.7% and 66.7%, p=0.0005) or RP (79.1% and 61.5%, p<0.0001). The 5-yr and 10-yr CSS and OS rates were similar across all three cohorts.
  
  
  
  Radiotherapy and RP provide equivalent CSS and OS. Extremely dose-escalated radiotherapy with ADT in particular offers improved systemic control when compared with either EBRT or RP. These data suggest that extremely dose-escalated radiotherapy with ADT might be the optimal upfront treatment for patients with biopsy GS 9-10 CaP.
  
  
  
  While some prostate cancers are slow-growing requiring many years, sometimes decades, of follow-up in order to compare between radiation and surgery, high-risk and very aggressive cancers follow a much shorter time course allowing such comparisons to be made and updated as treatments, especially radiation, rapidly evolve. We showed that radiation-based treatments and surgery, with contemporary standards, offer equivalent survival for patients with very aggressive cancers (defined as Gleason score 9-10). Extremely-dose escalated radiotherapy with short-course androgen deprivation therapy offered the least risk of developing metastases, and equivalent long term survival.
authors.affiliation: Department of Radiation Oncology, University of California, Los Angeles, CA, USA. Electronic address: aukishan@mednet.ucla.edu.
authors.forename: Amar U
authors.initials: AU
authors.lastname: Kishan
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Talha
authors.initials: T
authors.lastname: Shaikh
authors.affiliation: Department of Radiation Oncology, University of California, Los Angeles, CA, USA.
authors.forename: Pin-Chieh
authors.initials: PC
authors.lastname: Wang
authors.affiliation: Department of Urology, University of California, Los Angeles, CA, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Reiter
authors.affiliation: Department of Pathology, University of California, Los Angeles, CA, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Said
authors.affiliation: Department of Radiation Oncology, University of California, Los Angeles, CA, USA.
authors.forename: Govind
authors.initials: G
authors.lastname: Raghavan
authors.affiliation: Department of Radiation Oncology, University of California, Los Angeles, CA, USA; Department of Radiation Oncology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Nickols
authors.affiliation: Department of Urology, University of California, Los Angeles, CA, USA; Department of Urology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Aronson
authors.affiliation: Department of Radiation Oncology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Sadeghi
authors.affiliation: Department of Radiation Oncology, University of California, Los Angeles, CA, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kamrava
authors.affiliation: Department of Radiation Oncology, University of California, Los Angeles, CA, USA.
authors.forename: David Jeffrey
authors.initials: DJ
authors.lastname: Demanes
authors.affiliation: Department of Radiation Oncology, University of California, Los Angeles, CA, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Steinberg
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Horwitz
authors.affiliation: Department of Radiation Oncology, University of California, Los Angeles, CA, USA.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Kupelian
authors.affiliation: Department of Radiation Oncology, University of California, Los Angeles, CA, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: King
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D001918:Brachytherapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011878:Radiotherapy; D012189:Retrospective Studies; D017211:Treatment Failure
chemical_list: D000726:Androgen Antagonists
keywords: Gleason 10; Gleason 9; Radical prostatectomy; Radiotherapy