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 | 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 | 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% | 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 |