title: EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer.
abstract: OBJECTIVE
  To present a summary of the 2013 version of the European Association of Urology (EAU) guidelines on the treatment of advanced, relapsing, and castration-resistant prostate cancer (CRPC).
  
  
  METHODS
  The working panel performed a literature review of the new data (2011-2013). The guidelines were updated, and levels of evidence and/or grades of recommendation were added to the text based on a systematic review of the literature that included a search of online databases and bibliographic reviews.
  
  
  RESULTS
  Luteinising hormone-releasing hormone (LHRH) agonists are the standard of care in metastatic prostate cancer (PCa). LHRH antagonists decrease testosterone without any testosterone surge, and they may be associated with an oncologic benefit compared with LHRH analogues. Complete androgen blockade has a small survival benefit of about 5%. Intermittent androgen deprivation results in noninferior oncologic efficacy when compared with continuous androgen-deprivation therapy (ADT) in well-selected populations. In locally advanced and metastatic PCa, early ADT does not result in a significant survival advantage when compared with delayed ADT. Relapse after local therapy is defined by prostate-specific antigen (PSA) values >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir and after radiation therapy (RT). Therapy for PSA relapse after RP includes salvage RT (SRT) at PSA levels <0.5 ng/ml and SRP or cryosurgical ablation of the prostate in radiation failures. Endorectal magnetic resonance imaging and 11C-choline positron emission tomography/computed tomography (PET/CT) are of limited importance if the PSA is <1.0 ng/ml; bone scans and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should include analysis of PSA and testosterone levels, and screening for cardiovascular disease and metabolic syndrome. Treatment of CRPC includes sipuleucel-T, abiraterone acetate plus prednisone (AA/P), or chemotherapy with docetaxel at 75mg/m(2) every 3 wk. Cabazitaxel, AA/P, enzalutamide, and radium-223 are available for second-line treatment of CRPC following docetaxel. Zoledronic acid and denosumab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications.
  
  
  CONCLUSIONS
  The knowledge in the field of advanced, metastatic, and castration-resistant PCa is rapidly changing. These EAU guidelines on PCa summarise the most recent findings and put them into clinical practice. A full version is available at the EAU office or at www.uroweb.org.
  
  
  RESULTS
  We present a summary of the 2013 version of the European Association of Urology guidelines on treatment of advanced, relapsing, and castration-resistant prostate cancer (CRPC). Luteinising hormone-releasing hormone (LHRH) agonists are the standard of care in metastatic prostate cancer (PCa). LHRH antagonists decrease testosterone without any testosterone surge, and they might be associated with an oncologic benefit compared with LHRH analogues. Complete androgen blockade has a small survival benefit of about 5%. Intermittent androgen deprivation results in noninferior oncologic efficacy when compared with continuous androgen-deprivation therapy (ADT) in well-selected populations. In locally advanced and metastatic PCa, early ADT does not result in a significant survival advantage when compared with delayed ADT. Relapse after local therapy is defined by prostate-specific antigen (PSA) values >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir and after radiation therapy. Therapy for PSA relapse after RP includes salvage radiation therapy at PSA levels <0.5 ng/ml and salvage RP or cryosurgical ablation of the prostate in radiation failures. Multiparametric magnetic resonance imaging and 11C-choline positron emission tomography/computed tomography (PET/CT) are of limited importance if the PSA is <1.0 ng/ml; bone scans, and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should include analysis of PSA and testosterone levels, and screening for cardiovascular disease and metabolic syndrome. Treatment of castration-resistant CRPC includes sipuleucel-T, abiraterone acetate plus prednisone (AA/P), or chemotherapy with docetaxel 75 mg/m(2) every 3 wk. Cabazitaxel, AA/P, enzalutamide, and radium-223 are available for second-line treatment of CRPC following docetaxel. Zoledronic acid and denosumab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications. The guidelines reported should be adhered to in daily routine to improve the quality of care in PCa patients. As we have shown recently, guideline compliance is only in the area of 30-40%.
authors: Department of Urology, RWTH University, Aachen, Germany. Electronic address: aheidenreich@ukaachen.de.
authors: Axel
authors: A
authors: Heidenreich
authors: Department of Urology, Klinikum Golzheim, Düsseldorf, Germany.
authors: Patrick J
authors: PJ
authors: Bastian
authors: Department of Medical Oncology, University Hospital Del Mar, Barcelona, Spain.
authors: Joaquim
authors: J
authors: Bellmunt
authors: Department of Radiation Therapy, CHU Grenoble, Grenoble, France.
authors: Michel
authors: M
authors: Bolla
authors: Department of Urology, University Hospital, Leuven, Belgium.
authors: Steven
authors: S
authors: Joniau
authors: Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: Theodor
authors: T
authors: van der Kwast
authors: Department of Oncology and Palliative Medicine, Velindre Hospital, Cardiff, UK.
authors: Malcolm
authors: M
authors: Mason
authors: Department of Urology, Russian Academy of Medical Science, Cancer Research Center, Moscow, Russia.
authors: Vsevolod
authors: V
authors: Matveev
authors: Department of Radiation Oncology, University Hospital, Ulm, Germany.
authors: Thomas
authors: T
authors: Wiegel
authors: Department of Urology, Santa Maria Della Misericordia Hospital, Udine, Italy.
authors: Filiberto
authors: F
authors: Zattoni
authors: Department of Urology, University Hospital St Etienne, France.
authors: Nicolas
authors: N
authors: Mottet
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008297:Male; D009364:Neoplasm Recurrence, Local; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy / Q000379:methods / Q000592:standards*; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011878:Radiotherapy / Q000592:standards; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Abiraterone; Androgen deprivation; Chemotherapy; Denosumab; Docetaxel; EAU guidelines; Enzalutamide; Follow-up; Prostate cancer; Review; Salvage radiation therapy; Salvage radical prostatectomy; Zoledronic acid