Elsevier

European Urology

Volume 65, Issue 2, February 2014, Pages 467-479
European Urology

Guidelines
EAU Guidelines on Prostate Cancer. Part II: Treatment of Advanced, Relapsing, and Castration-Resistant Prostate Cancer

https://doi.org/10.1016/j.eururo.2013.11.002Get rights and content

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).

Evidence acquisition

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.

Evidence synthesis

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 75 mg/m2 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.

Patient summary

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/m2 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%.

Introduction

The most recent summary of the European Association of Urology (EAU) guidelines on prostate cancer (PCa) was published in 2011 [1]. This paper summarises the 2013 update of the EAU guidelines on the treatment of advanced, relapsing, and castration-resistant PCa (CRPC). The guidelines on screening, diagnosis, and treatment of clinically localised PCa were published in a separate paper. To facilitate evaluating the quality of the information provided, evidence levels and grade of recommendation have been inserted according to the general principles of evidence-based medicine [2].

Section snippets

Luteinising hormone-releasing hormone: analogues and antagonists

Luteinising hormone-releasing hormone (LHRH) agonists have become the standard of care in hormonal therapy because these agents have the potential of reversibility and enable the use of intermittent androgen-deprivation therapy (ADT), avoid the physical and psychological discomfort associated with orchiectomy, have a lower risk of cardiotoxicity than observed with diethylstilbestrol, and result in equivalent oncologic efficacy [3], [4].

In contrast to the agonists, LHRH antagonists result in a

Definition of recurrence

Following RP, a confirmed PSA value >0.2 ng/ml (ie, two consecutive increases) represents recurrent cancer [36]. Following RT, a PSA value of 2 ng/ml above the nadir after RT represents recurrent cancer (Phoenix classification [37]).

Local failure following RP might be predicted with an 80% probability by a PSA increase >3 yr after RP, a PSA DT >11 mo, a Gleason score <7, and stage ≤pT3a pN0, pTx R1. Systemic failure following RP might be predicted with >80% accuracy by a PSA increase <1 yr

Summary

The present text represents a summary. For more detailed information and a full list of references, refer to the full-text version. These EAU guidelines (ISBN 978-90-79754-71-7) are available at the EAU Web site: http://www.uroweb.org/guidelines/online-guidelines/.

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  • Cited by (0)

    1

    Chair of the EAU Prostate Cancer Guidelines Group, 2008 to March 2013.

    2

    Chair of the EAU Prostate Cancer Guidelines Group since March 2013.

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