Guidelines

Prostate Cancer

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, a geriatrician 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): Dr. A. Farolfi, Dr. D. Oprea-Lager, Prof.Dr. O. Rouvière and Dr. I.G. Schoots.

All radiotherapy (RT) 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.

The International Society of Urological Pathology is represented by Prof.Dr. T. van der Kwast.

Dr. S. O’Hanlon, consultant geriatrician, representing the International Society of Geriatric Oncology (SOIG) contributed to the sections addressing life expectancy, health status and quality of life in particular.

Dr. E. Briers, expert Patient Advocate Hasselt-Belgium representing the patient voice as delegated by the European Prostate Cancer Coalition/Europa UOMO.

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/.

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 2022 document presents a limited update of the 2021 EAU-EANM-ESTRO-ESUR-ISUP-SIOG 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.

All chapters of the 2022 PCa Guidelines have been updated. New data have been included in the following sections, resulting in new sections, and new and revised recommendations:

4.3 Clinically significant prostate cancer

4 5.1.2.4. Risk assessment to determine the need for biopsy

•4 5.2.1.2 Repeat PSA testingTable 5.5: Risk data table of clinically significant prostate cancer (csPCa), related to PI-RADS score and PSA-D categories in biopsy-naive men, clinically suspected of having significant disease

•Section 5.2.7.1.4 Towards ‘extended’ MRI-directed biopsy?

5.2.3.4 Guidelines for risk-assessment of asymptomatic men

Recommendation

Strength rating

In asymptomatic men with a prostate-specific antigen (PSA) level between 3–10 ng/mL
and a normal digital rectal examination, repeat the PSA test prior to further investigations.

Weak

5.2.8 Summery of evidence and guidelines for prostate biopsies

Summary of evidence

LE

Literature review including multiple biopsy schemes suggests that a 10 to 12-core scheme is optimal in the majority of initial and repeat biopsy patients, dependent on prostate size. These biopsy schemes should be heavily weighted towards the lateral aspect and the apex of the prostate to maximize peripheral zone sampling [3].

3

A systematic review and meta-analysis comparing MRI-targeted transrectal biopsy to MRI-targeted transperineal biopsy, analysing 8 studies, showed a higher sensitivity for detection of csPCa when the transperineal approach was used (86% vs. 73%).

2

Current literature, including systematic reviews and meta-analyses, does not show a clear superiority of one image-guided technique (cognitive guidance, US/MR fusion software or direct in-bore guidance) over the other.

2

Recommendations

Strength rating

At least 8 systematic biopsies are recommended in prostates with a size of about
30 cc and 10 to 12 core biopsies are recommended in larger prostates, with > 12 cores not being significantly more conclusive.

Strong

Transperineal biopsies are preferred over transrectal biopsies.

Strong

Where MRI has shown a suspicious lesion MR-targeted biopsy can be obtained through cognitive guidance, US/MR fusion software or direct in-bore guidance.

Weak

5.2.8.2.1 Recommended terminology for reporting prostate biopsies

Recommendation

Strength rating

Adenocarcinoma, provide type and subtype, and presence or absence of cribriform pattern.

Strong

5.3.5 Summary of evidence and guidelines for staging of prostate cancer

Summary of evidence

LE

PSMA PET/CT is more accurate for staging than CT and bone scan for high-risk disease but to date no outcome data exist to inform subsequent management.

1b

Recommendation

Strength rating

High-risk localised disease/locally advanced disease

When using PSMA PET or whole body MRI to increase sensitivity, be aware of the lack of outcome data of subsequent treatment changes.

Strong

•6.1.4.1.1.3.4. Radiopharmaceutical therapy

6.1.6 General guidelines for the treatment of prostate cancer

Recommendations

Strength rating

Surgical treatment

Do not perform nerve-sparing surgery when there is a risk of ipsilateral extracapsular extension (based on cT stage, ISUP grade, magnetic resonance imaging, or with this information combined into a nomogram).

Weak

Radiotherapeutic treatment

Offer low-dose rate (LDR) brachytherapy monotherapy to patients with good urinary function and low- or intermediate-risk disease with ISUP grade 2 and < 33% of biopsy cores involved.

Strong

Offer LDR or high-dose rate (HDR) brachytherapy boost combined with IMRT/VMAT plus IGRT to patients with good urinary function intermediate-risk disease with ISUP G3 and/or PSA 10-20 ng/mL.

Weak

Offer LDR or HDR brachytherapy boost combined with IMRT /VMAT plus IGRT to patients with good urinary function and high-risk and/or locally advanced disease.

Weak

•6.2.1.2.1 ADT monotherapy

6.2.1.3 Summary of evidence and guidelines for the treatment of low-risk disease

Summary of evidence

LE

Systematic biopsies have been scheduled in AS protocols, the number and frequency of biopsies varied, there is no approved standard.

NR

Recommendations

Strength rating

Active surveillance (AS)

Selection of patients

If MRI is not available, per-protocol confirmatory prostate biopsies should be performed

Weak

Follow-up of patients

Repeat biopsies should be performed at least once every 3 years for 10 years.

Weak

In case of PSA progression or change in DRE or MRI findings, do not progress to active treatment without a repeat biopsy.

Strong

Active treatment

Radiotherapeutic treatment

Offer low-dose rate brachytherapy to patients with low-risk PCa and good urinary function.

Strong

6.2.2.5 Guidelines for the treatment of intermediate-risk disease

Recommendations

Strength rating

Active surveillance (AS)

Offer AS to highly selected patients with ISUP grade group 2 disease (i.e. < 10%
pattern 4, PSA <10 ng/mL, < cT2a, low disease extent on imaging and low biopsy extent [defined as < 3 positive cores and cancer involvement < 50% core involvement [CI]/per core]), or another single element of intermediate-risk disease with low disease extent on imaging and low biopsy extent, accepting the potential increased risk of metastatic progression.

Weak

Patients with ISUP grade group 3 disease must be excluded from AS protocols.

Strong

Re-classify patients with low-volume ISUP grade group 2 disease included in AS protocols, if repeat non-MRI-based systematic biopsies performed during monitoring reveal > 3 positive cores or maximum CI > 50%/core of ISUP 2 disease.

Weak

Radiotherapeutic treatment

Offer low-dose rate brachytherapy to patients with good urinary function and favourable intermediate-risk disease.

Strong

Offer low-dose rate brachytherapy boost combined with IMRT/VMAT plus IGRT to patients with good urinary function and unfavourable intermediate-risk disease, in combination with short-term androgen deprivation therapy (ADT) (4–6 months).

Weak

Offer high-dose rate brachytherapy boost combined with IMRT/VMAT plusIGRT to patients with good urinary function and unfavourable intermediate-risk disease, in combination with short-term ADT (4–6 months).

Weak

In patients not willing to undergo ADT, use a total dose of IMRT/VMAT plus IGRT (76–78 Gy) or moderate hypofractionation (60 Gy/20 fx in 4 weeks or 70 Gy/28 fx in 6 weeks) or a combination with LDR or HDR brachytherapy boost.

Weak

6.2.3.4 Guidelines for radical treatment of high-risk localised disease

Recommendation

Strength rating

Radiotherapeutic treatment

In patients with high-risk localised disease and good urinary function, use IMRT/VMAT plus IGRT with brachytherapy boost (either high-dose rate or low-dose rate), in combination with long-term ADT (2 to 3 years).

Weak

6.2.4.5 Guidelines for radical treatment of locally-advanced disease

Recommendation

Strength rating

Radiotherapeutic treatment

Offer patients with locally advanced disease and good urinary function, IMRT/VMAT plus IGRT with brachytherapy boost (either high-dose rate or low-dose rate), in combination with long-term ADT.

Weak

Prescribe 2 years of abiraterone when offering IMRT/VMAT plus IGRT to the prostate plus pelvis (for cN1) in combination with long-term ADT, for M0 patients with cN1 or > 2 high-risk factors (cT3–4, Gleason > 8 or PSA > 40 ng/mL).

Strong

6.3.4.4 Summary of evidence and guidelines for imaging in patients with biochemical recurrence

Summary of evidence

LE

After RP there is no specific PSA threshold defining recurrence.

NR

6.4.9 Guidelines for the first-line treatment of metastatic disease

Recommendations

Strength rating

Offer luteinising hormone-releasing hormone (LHRH) antagonists or orchiectomy before starting ADT, especially to patients with impending clinical complications like spinal cord compression or bladder outlet obstruction.

Strong

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

Strong

6.5.15 Guidelines for systematic treatments of castrate-resistant disease

Recommendation

Strength rating

Novel agents

Offer 177Lu-PSMA-617 to pre-treated mCRPC patients with one or more metastatic lesions, highly expressing PSMA (exceeding the uptake in the liver) on the diagnostic radiolabelled PSMA PET/CT scan.

Strong