Elsevier

European Urology

Volume 59, Issue 4, April 2011, Pages 572-583
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.2011.01.025Get rights and content

Abstract

Objectives

Our aim is to present a summary of the 2010 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 emerging from 2007 to 2010. The guidelines were updated, and the levels of evidence (LEs) and/or grades of recommendation (GR) were added to the text based on a systematic review of the literature, which 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). Although LHRH antagonists decrease testosterone without any testosterone surge, their clinical benefit remains to be determined. Complete androgen blockade has a small survival benefit of about 5%. Intermittent androgen deprivation (IAD) results in equivalent 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 after radiation therapy (RT). Therapy for PSA relapse after RP includes salvage RT at PSA levels <0.5 ng/ml and salvage RP or cryosurgical ablation of the prostate in radiation failures. Endorectal magnetic resonance imaging and 11C-choline positron emission tomography/computed tomography (CT) are of limited importance if the PSA is <2.5 ng/ml; bone scans and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should include screening for the metabolic syndrome and an analysis of PSA and testosterone levels. Treatment of castration-resistant prostate cancer (CRPC) includes second-line hormonal therapy, novel agents, and chemotherapy with docetaxel at 75 mg/m2 every 3 wk. Cabazitaxel as a second-line therapy for relapse after docetaxel might become a future option. Zoledronic acid and denusomab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications.

Conclusion

The knowledge in the field of advanced, metastatic, and CRPC 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 online at www.uroweb.org.

Introduction

The most recent summary of the European Association of Urology (EAU) guidelines on PCa was published in 2008 [1]. This paper summarises the 2010 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 have been published in a separate paper. To facilitate evaluating the quality of the information provided, we inserted LEs and GR according to a modified classification system from the Oxford Centre for Evidence-Based Medicine levels of evidence [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 for reversibility and enable the use of IAD therapy.

  • Avoid the physical and psychological discomfort associated with orchiectomy.

  • Have a lower risk of cardiotoxicity as observed with diethylstilbestrol.

  • Result in equivalent oncologic efficacy [3], [4].

In contrast to the agonists, LHRH antagonists result in a rapid decrease in luteinising hormone,

Definition of recurrence

Following RP, a confirmed PSA value >0.2 ng/ml (ie, two consecutive increases) represents recurrent cancer [38]. Following radiation therapy (RT), a PSA value of 2 ng/ml above the nadir after RT represents recurrent cancer [39].

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 after RP,

Summary

The present text represents a summary, and for more detailed information and a full list of references, refer to the full-text version. These EAU guidelines (ISBN 978-90-79754-70-0) are available on the EAU Web site (http://www.uroweb.org/guidelines/online-guidelines/).

References (90)

  • H. Isbarn et al.

    Androgen deprivation therapy for the treatment of prostate cancer: consider both benefits and risks

    Eur Urol

    (2009)
  • C.C. Schulman et al.

    Testosterone measurement in patients with prostate cancer

    Eur Urol

    (2010)
  • M. Roach et al.

    Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference

    Int J Radiat Biol Phys

    (2006)
  • M.L. Cher et al.

    Limited role of radionuclide bone scintigraphy in patients with prostate specific antigen elevations after radical prostatectomy

    J Urol

    (1998)
  • C.J. Kane et al.

    Limited value of bone scintigraphy and computed tomography in assessing biochemical failure after radical prostatectomy

    Urology

    (2003)
  • A.J. Breeuwsma et al.

    Detection of local, regional, and distant recurrence in patients with PSA relapse after external-beam radiotherapy using (11)C-choline positron emission tomography

    Int J Radiat Oncol Biol Phys

    (2010)
  • G. Goldner et al.

    Is the Roach formula predictive for biochemical outcome in prostate cancer patients with minimal residual disease undergoing local radiotherapy after radical prostatectomy?

    Radiother Oncol

    (2010)
  • L.F. Da Pozzo et al.

    Long-term follow-up of patients with prostate cancer and nodal metastases treated by pelvic lymphadenectomy and radical prostatectomy: the positive impact of adjuvant radiotherapy

    Eur Urol

    (2009)
  • G.D. Grossfeld et al.

    Predictors of secondary cancer treatment in patients receiving local therapy for prostate cancer: data from cancer of the prostate strategic urologic research endeavor

    J Urol

    (2002)
  • A.J. Stephenson et al.

    Morbidity and functional outcomes of salvage radical prostatectomy for locally recurrent prostate cancer after radiation therapy

    J Urol

    (2004)
  • A. Heidenreich et al.

    Prognostic parameters, complications, and oncologic and functional outcome of salvage radical prostatectomy for locally recurrent prostate cancer after 21st-century radiotherapy

    Eur Urol

    (2010)
  • L.L. Pisters et al.

    The efficacy and complications of salvage cryotherapy of the prostate

    J Urol

    (1997)
  • R.D. Cespedes et al.

    Long-term follow-up of incontinence and obstruction after salvage cryosurgical ablation of the prostate: results in 143 patients

    J Urol

    (1997)
  • M.L. Eisenberg et al.

    Partial salvage cryoablation of the prostate for recurrent prostate cancer after radiotherapy failure

    Urology

    (2008)
  • M. Warmuth et al.

    Systematic review of the efficacy and safety of high-intensity focussed ultrasound for the primary and salvage treatment of prostate cancer

    Eur Urol

    (2010)
  • F.-J. Murat et al.

    Mid-term results demonstrate salvage high-intensity focused ultrasound (HIFU) as an effective and acceptably morbid salvage treatment option for locally radiorecurrent prostate cancer

    Eur Urol

    (2009)
  • H.I. Scher et al.

    Prostate Cancer Foundation/Department of Defense Prostate Cancer Clinical Trials Consortium. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study

    Lancet

    (2010)
  • A.V. D’Amico et al.

    Interval to testosterone recovery after hormonal therapy for prostate cancer and risk of death

    Int J Radiat Oncol Biol Phys

    (2009)
  • J.M. Fitzpatrick et al.

    Optimizing treatment for men with advanced prostate cancer: expert recommendations and the multidisciplinary approach

    Crit Rev Oncol Hematol

    (2008)
  • Y. Loriot et al.

    The interval from the last cycle of docetaxel-based chemotherapy to progression is associated with the efficacy of subsequent docetaxel in patients with prostate cancer

    Eur J Cancer

    (2010)
  • C. Buonerba et al.

    Docetaxel rechallenge in castration-resistant prostate cancer: scientific legitimacy of common clinical practice

    Eur Urol

    (2010)
  • Modified from Oxford Centre for Evidence-Based Medicine Levels of Evidence (May 2001). Produced by Bob Phillips, Chris...
  • D.G. McLeod

    Hormonal therapy: historical perspective to future directions

    Urology

    (2003)
  • J. Seidenfeld et al.

    Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis

    Ann Intern Med

    (2000)
  • L. Klotz et al.

    The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer

    BJU Int

    (2008)
  • A.V. Kaisary et al.

    Is there a role for antiandrogen monotherapy in patients with metastatic prostate cancer?

    Prost Cancer Prost Dis

    (2001)
  • C.J. Tyrrell et al.

    Casodex® 10-200 mg daily, used as monotherapy for patients with advanced prostate cancer: an overview of the efficacy, tolerability and pharmacokinetics from three phase II dose-ranging studies. Casodex Study Group

    Eur Urol

    (1998)
  • C.J. Tyrrell et al.

    A randomised comparison of ‘Casodex®’ (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer

    Eur Urol

    (1998)
  • J.W. Moul

    Twenty years of controversy surrounding combined androgen blockade for advanced prostate cancer

    Cancer

    (2009)
  • N.A. Cruz Guerra

    Outcomes from the use of maximal androgen blockade in prostate cancer at health area with reference hospital type 2 (1st part). Quality of life: application of EORTC QLQ-C30 instrument

    Arch Esp Urol

    (2009)
  • M. Hussain et al.

    Southwest Oncology Group Trial 9346 (INT-0162). Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: data from Southwest Oncology Group Trial 9346 (INT-0162)

    J Clin Oncol

    (2006)
  • E.Y. Yu et al.

    Duration of first off-treatment interval is prognostic for time to castration resistance and death in men with biochemical relapse of prostate cancer treated on a prospective trial of intermittent androgen deprivation

    J Clin Oncol

    (2010)
  • L. Boccon-Gibod et al.

    The role of intermittent androgen deprivation in prostate cancer

    BJU Int

    (2007)
  • U.E. Studer et al.

    Immediate or deferred androgen deprivation for patients with prostate cancer not suitable for local treatment with curative intent: European Organisation for Research and Treatment of Cancer (EORTC) Trial 30891

    J Clin Oncol

    (2006)
  • D.P. Byar

    Proceedings: the Veterans Administration Co-operative Urological Research Group studies of cancer of the prostate

    Cancer

    (1973)
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