title: Radical radiotherapy in high-risk prostate cancer patients with high or ultra-high initial PSA levels: a single institution analysis.
abstract: OBJECTIVE
  Purpose of this study is to analyze outcomes and pre-treatment prognostic factors in high-risk prostate cancer patients with initial PSA ≥ 20 ng/mL, treated with high-dose external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) in a single institution.
  
  
  METHODS
  Between March 2003 and December 2011, 155 consecutive high-risk prostate cancer patients (a) presenting with pre-treatment PSA level ≥ 20 ng/mL, (b) treated with definitive EBRT, and (c) with a minimum follow-up of 24 months were included in this retrospective analysis. Phoenix definition was used to define biochemical control. Primary endpoints were as follows: biochemical disease-free survival (bDFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS) and overall survival (OS). Multivariate analysis was performed to determine the independent prognostic impact of pre-treatment clinical factors [T stage, PSA, and Gleason score (GS)].
  
  
  RESULTS
  At a median follow-up time of 62 months, actuarial bDFS, DMFS, CSS, and OS at 5 years were 64.8, 85.2, 95.8, and 94.4 %, respectively. On multivariate analysis, only GS was significantly associated with three clinical endpoints (bDFS: HR 1.6; p = 0.022, CSS: HR 4.27, p = 0.044, OS: HR 2.6; p = 0.038). Pre-treatment zenith PSA was associated only with bDFS (HR 1.87; p = 0.027).
  
  
  CONCLUSIONS
  Patients with "high" PSA levels (≥ 20 ng/mL) showed favorable clinical outcomes, supporting the role of local radiotherapy as primary therapy in combination with long-term ADT in patients with high PSA levels at diagnosis. A GS of 8-10 is the strongest predictor of outcome.
authors.affiliation: Radiation Oncology, San Giovanni Battista Hospital, University of Torino, 10126 Turin, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Guarneri
authors.forename: Angela
authors.initials: A
authors.lastname: Botticella
authors.forename: Andrea Riccardo
authors.initials: AR
authors.lastname: Filippi
authors.forename: Andrea
authors.initials: A
authors.lastname: Ruggieri
authors.forename: Cristina
authors.initials: C
authors.lastname: Piva
authors.forename: Fernando
authors.initials: F
authors.lastname: Munoz
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ragona
authors.forename: Paolo
authors.initials: P
authors.lastname: Gontero
authors.forename: Umberto
authors.initials: U
authors.lastname: Ricardi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality / Q000532:radiotherapy*; D011829:Radiation Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D007987:Gonadotropin-Releasing Hormone; D017430:Prostate-Specific Antigen
references.citation: Urol Oncol. 2010 Sep-Oct;28(5):557-67
references.pmid: 20816616
references.citation: J Clin Oncol. 2008 May 20;26(15):2497-504
references.pmid: 18413638
references.citation: Eur Urol. 2012 Jun;61(6):1096-106
references.pmid: 22386839
references.citation: J Clin Oncol. 2010 Mar 1;28(7):1117-23
references.pmid: 20124165
references.citation: N Engl J Med. 2009 Jun 11;360(24):2516-27
references.pmid: 19516032
references.citation: Int J Radiat Oncol Biol Phys. 2012 Mar 15;82(4):1397-404
references.pmid: 21665379
references.citation: J Urol. 2006 Sep;176(3):991-5
references.pmid: 16890678
references.citation: J Clin Oncol. 2010 Mar 1;28(7):1106-11
references.pmid: 20124169
references.citation: Int J Radiat Oncol Biol Phys. 2008 Mar 15;70(4):1124-9
references.pmid: 18313526
references.citation: Eur Urol. 2011 Jan;59(1):61-71
references.pmid: 21056534
references.citation: Int J Radiat Oncol Biol Phys. 2011 Jun 1;80(2):445-52
references.pmid: 20615632
references.citation: Cancer. 2010 Nov 15;116(22):5226-34
references.pmid: 20690197
references.citation: Int J Radiat Oncol Biol Phys. 2011 Dec 1;81(5):1279-85
references.pmid: 20932659
references.citation: Int J Radiat Oncol Biol Phys. 2002 Aug 1;53(5):1097-105
references.pmid: 12128107
references.citation: BJU Int. 2012 Sep;110(6 Pt B):E192-8
references.pmid: 22313515
references.citation: J Urol. 2012 Apr;187(4):1259-65
references.pmid: 22335870
references.citation: Int J Radiat Oncol Biol Phys. 2006 Jul 15;65(4):965-74
references.pmid: 16798415
references.citation: BJU Int. 2011 Oct;108(7):1093-100
references.pmid: 21392220
references.citation: Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):646-55
references.pmid: 17531401
references.citation: Int J Radiat Oncol Biol Phys. 2012 Jul 15;83(4):e525-30
references.pmid: 22483701
references.citation: BJU Int. 2013 Mar;111(3):381-8
references.pmid: 22758210