title: High-risk prostate cancer: from definition to contemporary management.
abstract: BACKGROUND
  High-risk prostate cancer (PCa) is a potentially lethal disease. It is clinically important to identify patients with high-risk PCa early on because they stand to benefit the most from curative therapy. Because of recent advances in PCa management, a multimodal approach may be advantageous.
  
  
  OBJECTIVE
  Define high-risk PCa, and identify the best diagnostic and treatment patterns for patients with clinically localized and locally advanced disease. A critical analysis of published results following monomodal and/or multimodal therapy for high-risk PCa patients was also performed.
  
  
  METHODS
  A review of the literature was performed using the Medline, Embase, Scopus, and Web of Science databases as well as the Cochrane Database of Systematic Reviews.
  
  
  RESULTS
  High-risk PCa accounts for ≤ 15% of all new diagnoses. Compared with patients with low- and intermediate-risk PCa, patients with high-risk PCa are at increased risk of treatment failure. Unfortunately, no contemporary randomized controlled trials comparing different treatment modalities exist. Evaluation of the results published to date shows that no single treatment can be universally recommended. Most often, a multimodal approach is warranted to optimize patient outcomes.
  
  
  CONCLUSIONS
  A significant minority of patients continue to present with high-risk PCa, which remains lethal in some cases. Outcomes following treatment of men with high-risk tumors have not substantially improved over time. However, not all high-risk patients are at the same risk of PCa progression and death. At present, a multimodal approach seems the best way to achieve acceptable outcomes for high-risk PCa patients.
authors.affiliation: Department of Urology, Klinikum der Universität München-Campus Großhadern, Ludwig-Maximilians-Universität, Munich, Germany. patrick.bastian@med.uni-muenchen.de
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bastian
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Boorjian
authors.forename: Alberto
authors.initials: A
authors.lastname: Bossi
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.forename: Axel
authors.initials: A
authors.lastname: Heidenreich
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Freedland
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.forename: Mack
authors.initials: M
authors.lastname: Roach
authors.forename: Fritz
authors.initials: F
authors.lastname: Schröder
authors.forename: Hein
authors.initials: H
authors.lastname: van Poppel
authors.forename: Christian G
authors.initials: CG
authors.lastname: Stief
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Stephenson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zelefsky
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D019317:Evidence-Based Medicine; D006801:Humans; D008197:Lymph Node Excision; D008297:Male; D020360:Neoadjuvant Therapy; D018579:Patient Selection; D011237:Predictive Value of Tests; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D018714:Radiotherapy, Adjuvant; D018570:Risk Assessment; D012307:Risk Factors; D009626:Terminology as Topic; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal