Prostate Cancer

Full Text Guidelines Summary of Changes Scientific Publications & Appendices Pocket Guidelines Archive Panel

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N. Mottet (Chair), P. Cornford (Vice-chair), R.C.N. van den Bergh, E. Briers (Patient Representative), M. De Santis, S. Fanti, S. Gillessen, J. Grummet, A.M. Henry, T.B. Lam, M.D. Mason, T.H. van der Kwast, H.G. van der Poel, O. Rouvière, I.G. Schoots, D. Tilki, T. Wiegel
Guidelines Associates: T. Van den Broeck, M. Cumberbatch, N. Fossati, G. Gandaglia, N. Grivas, M. Lardas, M. Liew, L. Moris, D.E. Oprea-Lager, P-P.M. Willemse

1.INTRODUCTION

1.1.Aims and scope

The Prostate Cancer (PCa) Guidelines Panel have prepared this guidelines document to assist medical professionals in the evidence-based management of PCa.

It must be emphasised that clinical guidelines present the best evidence available to the experts but following guideline recommendations will not necessarily result in the best outcome. Guidelines can never replace clinical expertise when making treatment decisions for individual patients, but rather help to focus decisions - also taking personal values and preferences/individual circumstances of patients into account. Guidelines are not mandates and do not purport to be a legal standard of care.

1.2.Panel composition

The PCa Guidelines Panel consists of an international multidisciplinary group of urologists, radiation oncologists, medical oncologists, radiologists, a pathologist and a patient representative.

All imaging sections in the text have been developed jointly with the European Society of Urogenital Radiology (ESUR) and the European Association of Nuclear Medicine (EANM). Representatives of the ESUR and the EANM in the PCa Guidelines Panel are (in alphabetical order): Prof.Dr. S. Fanti, Prof.Dr. O Rouvière and Dr. I.G. Schoots.

All radiotherapy sections have been developed jointly with the European Society for Radiotherapy & Oncology (ESTRO). Representatives of ESTRO in the PCa Guidelines Panel are (in alphabetical order): Prof.Dr. A.M. Henry, Prof.Dr. M.D. Mason and Prof.Dr. T. Wiegel.

All experts involved in the production of this document have submitted potential conflict of interest statements which can be viewed on the EAU website Uroweb: https://uroweb.org/guideline/prostate-cancer/?type=panel.

1.2.1.Acknowledgement

The PCa Guidelines Panel gratefully acknowledges the assistance and general guidance provided by Prof.Dr. M. Bolla, honorary member of the PCa Guidelines Panel.

1.3.Available publications

A quick reference document (Pocket guidelines) is available, both in print and as an app for iOS and Android devices. These are abridged versions which may require consultation together with the full text version. Several scientific publications are available [1,2] as are a number of translations of all versions of the PCa Guidelines.

All documents can be accessed on the EAU website: http://uroweb.org/guideline/prostate-cancer/.

1.4.Publication history and summary of changes

1.4.1.Publication history

The EAU PCa Guidelines were first published in 2001. This 2020 document presents a limited update of the 2019 PCa Guidelines publication.

1.4.2.Summary of changes

The literature for the complete document has been assessed and updated based upon a review of all recommendations and creation of appropriate GRADE forms. Evidence summaries and recommendations have been amended throughout the current document and several new sections have been added.

The following sections have been revised, or were added:

  • Section 3.2.1 - Family history/genetics, has been updated resulting in a new recommendation.

5.1.3 Guidelines for screening and early detection

Recommendation for all patients

LE

Strength rating

Offer early PSA testing to well-informed men at elevated risk of having PCa:

men carrying BRCA2 mutations > 40 years of age.

2b

Strong


  • Chapter 4 - Classification and staging systems, including two recommendations.

4.4 Guideline for classification and staging systems

Recommendations

Strength rating

Use the Tumour, Node, Metastasis (TNM) classification for staging of PCa.

Strong

Use the International Society of Urological Pathology (ISUP) 2014 system for grading of PCa.

Strong


  • Section 5.2.4.2.7.3 - The role of risk-stratification, has been revised with the inclusion of a new table (Table 5.2.4.2: Impact of the PSA density on csPCa detection rates in patients with negative mpMRI findings) and amended recommendations.

5.2.4.4 Guidelines for imaging in PCa detection

Introductory statement

LE

Systematic biopsy is an acceptable approach in case mpMRI is unavailable.

3

Recommendations for all patients

LE

Strength rating

Do not use mpMRI as an initial screening tool.

3

Strong

Adhere to PI-RADS guidelines for multiparametric magnetic resonance imaging (mpMRI) acquisition and interpretation and evaluate mpMRI results in multidisciplinary meetings with pathological feedback.

3

Strong


  • Section 5.3.2.3 - Prostate-specific membrane antigen-based PET/CT, has been completely revised.
  • Section - 5.2.7.3 Tissue-based prognostic biomarker testing, includes the findings of a recently published multidisciplinary Guideline, resulting in one recommendation to be changed from 'Strong'to 'Weak'.

5.2.2.6 Guidelines for risk-assessment of asymptomatic men

Recommendation

Strength rating

To avoid unnecessary biopsies, offer further risk-assessment to asymptomatic men
with a normal digital rectal examination and a prostate-specific antigen level between 2-10 ng/mL prior to performing a prostate biopsy. Use one of the following tools:

an additional serum or urine-based test.

Weak


  • Chapter 5.2 - Clinical diagnosis, in particular Section 5.2.6 - Prostate biopsy procedure, was amended resulting in an changed recommendation.

5.2.8 Guidelines for the clinical diagnosis of prostate cancer

Recommendation for all patients

LE

Strength rating

Do not offer non-targeted transition zone sampling at initial biopsies due to low detection rates.

2b

Weak


  • Section 6.1.2 - Radical prostatectomy, has been completely revised.
  • Section 6.1.3.1.3 - Hypofractionation, was revised, also including a new table (Table 6.1.8: Selected trials on hypofractionation for intact localised PCa).
  • Section 6.1.4 - Hormonal therapy, new Section 6.1.4.1.1.6.4 - Darolutamide, has been added.
  • Section 6.2.1 - Treatment of low-risk disease; the findings of an international collaborative multi-stakeholder consensus project addressing the deferred treatment with curative intent for localised have been incorporated, resulting in several changes to the recommendations for this section.

    New sections 6.2.1.1.3 - Imaging for treatment selection, 6.2.1.1.4 - Monitoring during active surveillance, and 6.2.1.1.5 - Active surveillance, when to change strategy, have been added. Due to the inclusion of new data, new sections and the findings of the international collaborative multi-stakeholder consensus project addressing the deferred treatment with curative intent for localised PCa, a number of recommendations were changed, and new recommendations have been added.

6.2.1.4 Guidelines for the treatment of low-risk disease

Recommendations

Strength rating

Active surveillance (AS)

Offer AS to patients with a life expectancy > 10 years and low-risk disease.

Strong

If a patient has had upfront multiparametric magnetic resonance imaging (mpMRI) followed by systematic and targeted biopsies there is no need for confirmatory biopsies.

Weak

Patients with intraductal and cribiform histology on biopsy should be excluded from AS.

Strong

If required perform mpMRI before a confirmatory biopsy.

Strong

Take both targeted biopsy (of any PI-RADS > 3 lesion) and systematic biopsy if a confirmatory biopsy is performed.

Strong

Perform serum prostate-specific antigen (PSA) assessment every 6 months.

Strong

Perform digital rectal examination (DRE) every 12 months.

Strong

Repeat biopsy should be performed if there is evidence of PSA progression, clinical progression on DRE or radiological progression on mpMRI.

Strong

During follow-up, if mpMRI is negative (i.e., PI-RADS < 2), and clinical suspicion of prostate cancer progression is low (e.g. low PSA velocity, long PSA doubling time), omit biopsy based on shared decision making with the patient.

Weak

Counsel patients about the possibility of needing further treatment in the future.

Strong

Other therapeutic options

Only offer whole gland treatment (such as cryotherapy, high-intensity focused ultrasound, etc.) or focal treatment within a clinical trial setting or well-designed prospective cohort study.

Strong


  • 6.2.2.4 - Other options for the primary treatment of intermediate-risk PCa (experimental therapies), has been revised.
  • Section 6.2.3 - Treatment of high-risk localised disease; due to the inclusion of new data, a recommendation was revised.

6.2.4.4 Guidelines for radical treatment of high-risk localised disease

Recommendation

Strength rating

Radical Prostatectomy (RP)

Offer RP to selected patients with high-risk localised PCa, as part of potential multi-modal therapy.

Strong


  • Section 6.2.4 - Treatment of locally-advanced prostate cancer, has been revised, also including a new section on the treatment of cN1 disease, resulting in a new recommendation:

6.2.4.5 Guidelines for radical treatment of locally-advanced disease

Recommendations

Strength rating

Radiotherapeutic treatments

Offer long-term ADT for at least two years.

Weak

Therapeutic options outside surgery and radiotherapy

Only offer ADT monotherapy to those patients unwilling or unable to receive any form of local treatment if they have a prostate-specific antigen (PSA)-doubling time < 12 months, and either a PSA > 50 ng/mL, a poorly-differentiated tumour or troublesome local disease-related symptoms.

Strong

Offer patients with cN1 disease a local treatment (either RP or external beam radiation therapy) plus long-term ADT.

Weak


  • Section 6.2.5 - Adjuvant treatment after radical prostatectomy, due to the inclusion of new data, two recommendations were revised.

6.2.5.6 Guidelines for adjuvant treatment options after radical prostatectomy

Recommendations

Strength rating

Offer adjuvant external-beam radiation therapy to the surgical field to highly selected patients.

Strong

Discuss three management options with patients with pN+ disease after an extended lymph node dissection, based on nodal involvement characteristics:

1. Offer adjuvant ADT;

2. Offer adjuvant ADT with additional radiotherapy;

3. Offer observation (expectant management) to a patient after eLND and < 2 nodes with microscopic involvement, and a PSA < 0.1 ng/mL and absence of extranodal extension.

Weak


  • Section 6.3.4 - The role of imaging in PSA-only recurrence, has been completely revised.
  • Due to the inclusion of new data in the second-line treatment modalities, two recommendations have been added.

6.3.9 Guidelines for second-line therapy after treatment with curative intent

Local salvage treatment

Strength rating

Recommendations for biochemical recurrence after radical prostatectomy

Offer PSA monitoring to patients with biochemical recurrence with low-risk features at relapse who may not benefit from intervention.

Weak

Offer hormonal therapy in addition to SRT to men with biochemical recurrence.

Weak


  • Section 6.4 - Treatment of metastatic prostate cancer, has been considerably revised with additional data (including new Section - 6.4.4.2.2 - Combination with the new hormonal treatments [abiraterone, ezalutamide]) and the inclusion of a new table (Table 6.4.5: Results from the ENZAMET and TITAN studies), necessitating changes to the recommendations.

6.4.9 Guidelines for the first-line treatment of metastatic disease

Recommendations

Strength rating

Offer immediate systemic treatment with androgen deprivation therapy (ADT) to palliate symptoms and reduce the risk for potentially serious sequelae of advanced disease (spinal cord compression, pathological fractures, ureteral obstruction) to M1 symptomatic patients.

Strong

Offer luteinising hormone-releasing hormone (LHRH) antagonists, especially to patients with an impending spinal cord compression or bladder outlet obstruction.

Weak

Offer surgery and/or local radiotherapy to any patient with M1 disease and evidence of impending complications such as spinal cord compression or pathological fracture.

Strong

Offer immediate systemic treatment to M1 patients asymptomatic from their tumour.

Weak

Discuss deferred ADT with well-informed M1 patients asymptomatic from their tumour since it lowers the treatment-related side-effects, provided the patient is closely monitored.

Weak

Offer short-term administration of an older generation androgen receptor (AR) antagonist to M1 patients starting LHRH agonist to reduce the risk of the 'flare-up' phenomenon.

Weak

Do not offer AR antagonists monotherapy to patients with M1 disease.

Strong

Offer ADT combined with chemotherapy (docetaxel) to patients whose first presentation is M1 disease and who are fit for docetaxel.

Strong

Offer ADT combined with abiraterone acetate plus prednisone or apalutamide or enzalutamide to patients whose first presentation is M1 disease and who are fit for the regimen.

Strong

Offer ADT combined with prostate radiotherapy to patients whose first presentation is M1 disease and who have low volume of disease by CHAARTED criteria.

Strong

Do not offer ADT combined with any local treatment (radiotherapy/surgery) to patients with high volume (CHAARTED criteria) M1 disease outside of clinical trials (except for symptom control).

Strong


  • Section 6.5 - Treatment; Castration-resistant PCa, has been updated, also including additional information general aspects (Section 6.5.1.2) and sequencing of drugs. New section 6.5.7 - Gallium prostate specific membrane antigen (PSMA) therapy, has been included. Recommendations were changed in sections:

6.5.13 Summary of evidence and guidelines for life-prolonging treatments of castrate-resistant disease

Recommendation

Strength rating

Treat patients with mCRPC with life-prolonging agents.

Base the choice of first-line treatment on the performance status, symptoms, comorbidities, location and extent of disease, patient preference, and on the previous treatment for hormone-sensitive metastatic PCa (HSPC) (alphabetical order: abiraterone, cabazitaxel, docetaxel, enzalutamide, radium-223, sipuleucel-T).

Strong

6.5.15 Guidelines for supportive care of castrate-resistant disease

These recommendations are in addition to appropriate systemic therapy.


Recommendation

Strength rating

Monitor serum calcium and offer calcium and vitamin D supplementation when prescribing either denosumab or bisphosphonates.

Strong

6.5.16 Guidelines for non-metastatic castrate-resistant disease

Recommendations

Strength rating

Offer apalutamide, darolutamide or enzalutamide to patients with M0 CRPC and a high risk of developing metastasis (PSA-DT < 10 months) to prolong time to metastases.

Strong


  • Chapter 7 - Follow-up, aside from revised data, includes new section 7.2.6 - Disease progression during androgen deprivation therapy.
  • Due to the inclusion of new publications, new recommendations were added to Chapter 8 - Quality of life outcomes in prostate cancer:

8.3.2.1 Guidelines for quality of life in men undergoing systemic treatments

Recommendation

Strength rating

Advise men on androgen deprivation therapy to maintain a healthy weight and diet, to stop smoking and have yearly screening for diabetes and hypercholesterolemia. Ensure that calcium and vitamin D meet recommended levels.

Strong

8.3.2.1 Guidelines for quality of life in men undergoing systemic treatments

Recommendations

Strength rating

Offer men starting on long-term androgen deprivation therapy dual emission X-ray absorptiometry (DEXA) scanning to assess bone mineral density.

Strong

Use the WHO FRAX tool to guide monitoring and treatment of bone mineral density in men on long term ADT.

Strong