This is a repository copy of EAU-EANM-ESTRO-ESUR-SIOG Prostate Cancer Guideline Panel Consensus Statements for Deferred Treatment with Curative Intent for Localised Prostate Cancer from an International Collaborative Study (DETECTIVE Study). White Rose Research Online URL for this paper: http://eprints.whiterose.ac.uk/152615/ Version: Supplemental Material Article: Lam, TBL, MacLennan, S, Willemse, P-PM et al. (66 more authors) (2019) EAU-EANM-ESTRO-ESUR-SIOG Prostate Cancer Guideline Panel Consensus Statements for Deferred Treatment with Curative Intent for Localised Prostate Cancer from an International Collaborative Study (DETECTIVE Study). European Urology, 76 (6). pp. 790-813. ISSN 0302-2838 https://doi.org/10.1016/j.eururo.2019.09.020 © 2019 Published by Elsevier B.V. on behalf of European Association of Urology. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/). 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More information and the full terms of the licence here: https://creativecommons.org/licenses/ Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ Appendix 1: List of collaborators EAU EANM - ESTRO - ESUR - SIOG Prostate Cancer Guidelines Panel European Association of Urology Research Foundation (EAU RF) European Urology EAU Section of Oncological Urology (ESOU) American Society of Clinical Oncology (ASCO) American Urological Association (AUA) European Society for Radiotherapy and Oncology (ESTRO) European Association of Urology Nurses (EAUN) Canadian Urological Association (CUA) International Society of Urological Pathology (ISUP) Urological Society of Australia and New Zealand (USANZ) European Society of Urogenital Radiology (ESUR) Urological Association of Asia (UAA) American Society for Radiation Oncology (ASTRO) Europa UOMO Red Sock Campaign Movember Foundation Appendix 2: DETECTIVE Delphi survey* *NOTE all participants saw the same questions in round 1 and round 2 of the Delphi. Two additional questions (suggested by participants in round 1) were included in round 2. These can be seen at the end of this appendix. MAIN QUESTIONS PAGE Please complete the following section which relates to background information. Part 1: Background information Name What is your main area of speciality? (please tick one that best apply to you) Urology Clinical or Radiation Oncology Medical Oncology Radiology Pathology General Practitioner Specialist Nurse Other please specify What treatment for localised prostate cancer do you specialise in? (you may tick more than Active surveillance one) Open radical prostatectomy Laparoscopic radical prostatectomy Robot-assisted radical prostatectomy External beam radiotherapy Three dimensional conformal radiotherapy (3D-CRT) Intensity modulated radiotherapy (IMRT) Volumetric modulated arc therapy (VMAT) Brachytherapy High Intensity Focussed Ultrasound (HIFU) Cryotherapy (cryosurgery) Focal therapy (including all types of energies and techniques) Other please specify Not directly involved with treatment for localised prostate cancer Unable to answer Part 2: Main questions regarding statements concerning deferred active treatment/active surveillance/active monitoring Please state your level of agreement for each of the following statements. On each page you will see a list of statements organised under the different domains in the patient management pathway for deferred active treatment/active surveillance/active monitoring. These include: (1) Patient eligibility, inclusion and exclusion criteria; (2) Monitoring and follow-up criteria; (3) Reclassification criteria; and (4) Outcome measures, definitions and thresholds. Each domain is sub-divided into the relevant sub-domains. You will be asked to score your agreement on a scale of 1- S S I U P you strongly believe should be included in this survey in the space provided in Section E (Domain 5: Additional statements) on the final page and remember to score any new statements that you suggest. A. Domain 1: Patient eligibility, inclusion and exclusion criteria I. Age and life expectancy Strongly Neither agree Strongly disagree nor disagree agree Statement 1 2 3 4 5 6 7 8 9 Unable to score 1. There is no lower nor upper age limit for inclusion as long as the appropriate life expectancy criterion is fulfilled 2. The appropriate life expectancy criterion for inclusion is: i. ii. 3. Life expectancy in everyday practice is best evaluated by: i. Performance status (e.g. ECOG, Karnofsky) ii. Co-morbidity index measure (e.g. Charlson) iii. Health status screening (e.g. Geriatric 8 screening tool) iv. Combination of performance status, co-morbidity index and health status screening II. R DA EAU Strongly Neither agree Strongly disagree nor disagree agree Statement 1 2 3 4 5 6 7 8 9 Unable to score 1. Low-risk disease: i. is an automatic inclusion criterion regardless of other disease factors ii. is excluded if the extent of disease is high based on biopsy core volume, length or number or proportion of core positivity iii. is excluded if the extent and/or stage of disease is high based on mpMRI iv. is excluded if mpMRI suggests biologically-aggressive disease 2. Gleason 3+4=7 (ISUP grade 2): i. is an automatic exclusion criterion ii. can be included only if favourable characteristics are present, including PSA (<10), clinical stage T 3. Gleason 4+3=7 (ISUP grade 3): i. is an automatic exclusion criterion. ii. can be included only if favourable characteristics are present, including PSA (<10), clinical stage T a) and biopsy characteristics (low core positivity) 4. PSA: i. >10ng/ml is an automatic exclusion criterion, regardless of other disease characteristics ii. >20ng/ml is an automatic exclusion criterion, regardless of other disease characteristics 5. PSA density: i. is an important inclusion criterion ii. 6. Clinical stage: T T ic exclusion criterion, regardless of other disease characteristics III. Pathology characteristics Strongly Neither agree Strongly disagree nor disagree agree Statement 1 2 3 4 5 6 7 8 9 Unable to score 1. Targeted biopsies should be reported separately from systematic biopsies 2. The extent of disease should be reported in: i. mm ii. % tumour volume (as a proportion of total volume of core) 3. ISUP grade (Gleason score) should be reported for each positive core 4. Percentage of Gleason pattern 4 carcinoma should be provided for each biopsy site with Gleason score 7 carcinoma 5. Intraductal and cribriform histology are exclusion criteria 6. When systematic biopsies are performed, the extent of disease based on histological characteristics (e.g. core length, core volume, core positivity, etc.) is an important inclusion/exclusion criterion 7. Extent of disease on histology is important even for Gleason 3+3=6/ISUP Grade 1 disease because it may lead to patients being excluded 8. The threshold of disease extent beyond which patients are automatically i. Core positivity >20% excluded based on systematic biopsy regardless of other disease ii. Core positivity >33% characteristics for Gleason 3+3=6/ISUP Grade 1 disease is: iii. C iv. Positive cores >2 v. Positive cores >3 vi. Core length >3mm vii. Core length >5mm 9. The threshold of disease extent beyond which patients are automatically i. Core positivity >20% excluded based on systematic biopsy regardless of other disease characteristics for Gleason 3+4=7/ISUP Grade 2 disease is: ii. Core positivity >33% C iv. Positive cores >2 v. Positive cores >3 vi. Core length >3mm vii. Core length >5mm viii. Any disease extent (because Gleason 3+4=7/ISUP Grade 2 is an automatic exclusion) IV. Imaging characteristics Strongly Neither agree Strongly disagree nor disagree agree Statement 1 2 3 4 5 6 7 8 9 Unable to score 1. If a patient has had upfront mpMRI followed by systematic and targeted biopsies, there is no need for confirmatory biopsies 2. If targeted biopsies based upon mpMRI images are performed, the number of positive cores is not an indicator of extent of disease nor tumour volume 3. The number of positive sextants based on systematic and/or targeted biopsies should be taken into account as an indicator of tumour volume 4. The volume of the dominant lesion seen on mpMRI (PI-RADS V2 ) should be taken into account as an indicator of tumour volume 5. For inclusion, prostate biopsies should be performed by: i. MRI-guided targeted biopsies (including in-bore, cognitive guidance or MRI fusion) without systematic biopsies ii. MRI-guided targeted biopsies (including in-bore, cognitive guidance or MRI fusion) with systematic biopsies iii. Transperineal template biopsies instead of MRI-guided biopsies iv. TRUS-guided systematic biopsies only 6. Tumour volume T M‘I D T ADC M‘I ion/exclusion criterion 8. For inclusion, all patients need an mpMRI at some point B. Domain 2: Monitoring and follow-up criteria I. Monitoring and follow-up Strongly Neither agree Strongly disagree nor disagree agree Statement 1 2 3 4 5 6 7 8 9 Unable to score During active surveillance in the first 2 years, men should i. Every 3 months have their PSA checked: ii. Every 6 months iii. Not checked at all During active surveillance after the first 2 years, men should i. Every 6 months have their PSA checked: ii. Every 12 months iii. Not checked at all During active surveillance, men should have a digital rectal i. Every 3 months examination (DRE): ii. Every 6 months iii. Every 12 months iv. Not needed During active surveillance, repeat biopsy should be i. Every 12 months performed: ii. Every 24 months iii. Every 48 months iv. At 1 year, 4 years and 7 years v. Not routinely pre-planned unless triggered vi. Triggered by a change in mpMRI (i.e. increase PI-RADS score, lesion volume or radiological T stage) vii. Triggered by PSA doubling time <3 years viii. Triggered by DRE progression If repeat biopsies are needed, they should be performed by: i. 10-12 core TRUS-guided ii. MRI-guided targeted biopsies (including in-bore, cognitive guidance or MRI fusion) without systematic biopsies iii. MRI-guided targeted biopsies (including in-bore, cognitive guidance or MRI fusion) with systematic biopsies iv. Transperineal template biopsies instead of MRI-guided biopsies v. TRUS-guided systematic biopsies C. Domain 3: Reclassification (i.e. leaving active surveillance for an active treatment) criteria I. Reclassification Criteria based on patient characteristics Strongly disagree Neither agree nor Strongly agree disagree Statement 1 2 3 4 5 6 7 8 9 Unable to score Reclassification should only apply to patients with a life expectancy of time of assessment ‘ time of assessment A ars A Patient anxiety or depression is a valid reason for triggering reclassification (including active treatment) Patient reluctance to undergo repeat biopsies or repeat imaging is a valid reason for triggering reclassification (including active treatment) II. Reclassification - Criteria based on PSA Strongly Neither agree Strongly disagree nor disagree agree Statement 1 2 3 4 5 6 7 8 9 Unable to score PSA progression is sufficient to indicate reclassification in the absence of other factors. A rise in PSA mandates re-biopsy irrespective of other findings. A rise in PSA mandates re-imaging of the patient. A shortening of PSA doubling time: 1. is sufficient to indicate reclassification in the absence of other factors 1. Should only indicate reclassification if it falls below a defined threshold 2. of < 36 months indicates reclassification 3. of < 24 months indicates reclassification 4. even if minimal would indicate reclassification if accompanied by other PSA-based parameter changes A rise in PSA above an absolute threshold: 1. of > 10 would indicate reclassification 2. of > 20 would indicate reclassification A PSA velocity: 1. of > 0.75/year would indicate reclassification 2. of > 1.0/year would indicate reclassification An increase in PSA density: 1. is sufficient to indicate reclassification in the absence of other factors 2. would indicate reclassification if accompanied by other PSA-based parameter changes A change in PSA parameters which by itself is not 1. changes in histology sufficient, would indicate reclassification if accompanied by: 2. changes in imaging III. Reclassification - Criteria based on histopathology (a) Criteria based on grade Strongly Neither agree Strongly disagree nor disagree agree Statement 1 2 3 4 5 6 7 8 9 Unable to score A higher Gleason score (or ISUP grade) on re-biopsy is required for reclassification (b) Criteria based on histopathological extent Strongly Neither agree Strongly disagree nor disagree agree Statement 1 2 3 4 5 6 7 8 9 Unable to score An increase in the number of positive cores on re-biopsy: 1. indicates re-classification (i.e. no threshold needed) 2. if > 2 cores on re-biopsy indicates reclassification 3. If > 3 cores on re-biopsy indicates reclassification An increase in the extent of core involvement: 1. indicates re-classification (i.e. no threshold needed) 2. If > 20% of a core indicates reclassification 3. If > 33% of a core indicates reclassification 4. If > 50% of a core indicates reclassification 5. Is not important for Gleason 3+3=6/ISUP Grade 1 disease IV. Reclassification - Criteria based on clinical examination Strongly Neither agree Strongly disagree nor disagree agree Statement 1 2 3 4 5 6 7 8 9 Unable to score An increase in the clinical T-category based on DRE , as the 1. If increase to cT2a, indicates reclassification sole criterion: 2. If increase to cT2b indicates reclassification 3. If increase to cT2c indicates reclassification V. Reclassification - Criteria based on imaging Strongly Neither agree Strongly disagree nor disagree agree Statement 1 2 3 4 5 6 7 8 9 Unable to score Radiological evidence of disease progression is sufficient to reclassify in the absence of other factors. Radiological evidence of progression mandates an image-directed biopsy. A new focus of cancer on repeat imaging indicates re- 1. Always classification 2. Only if accompanied by a re-biopsy I T -biopsy, PSA, etc.) indicates re- classification. An increase in the PI-RADS score indicates reclassification in the absence of other features. VI. Reclassification - Criteria based on patient preference Strongly Neither agree Strongly disagree nor disagree agree Statement 1 2 3 4 5 6 7 8 9 Unable to score Patient preference to switch to active treatment, regardless of other factors, should trigger reclassification. D. Domain 4: Outcome measures * NOTE this is the subset of questions which patients were asked also I. Primary outcome measures which must be measured and prioritised by all active surveillance programmes Strongly Neither agree Strongly disagree nor disagree agree Statement 1 2 3 4 5 6 7 8 9 Unable to score The following outcomes are critically important for active Overall survival (i.e. a measure of survival or death from all surveillance programmes to measure: causes, including natural causes) Prostate cancer-specific survival (i.e. a measure of survival or death from prostate cancer only, excluding other causes) Progression to metastatic disease (i.e. cancer spreading to other organs) Local progression (i.e. cancer getting bigger or more advanced locally) Symptomatic progression (i.e. cancer progressing locally to cause symptoms such as pelvic pain, bleeding in urine, difficulty in urinating, etc.) Re-classification (i.e. coming off active surveillance for active curative treatment e.g. surgery or radiotherapy) Urinary function (i.e. function relating to urinating) Sexual function (i.e. function relating to erection, libido, ejaculation, etc.) Overall quality of life (i.e. quality of life relating to general health and well-being) Anxiety Depression E. Domain 5: Additional statements or important outcomes included by survey participants (*NOTE asked to ALL PARTICIPANTS, INCLUDING PATIENTS) I. If you feel strongly that important statements or outcomes are missing from the survey, please include them below and include your judgement. They will be included in the next round of the survey. However, please restrict to critically important statements or outcomes only, as there is a limit to the number of statements allowable on the survey. Strongly disagree Neither agree nor Strongly agree disagree Statement 1 2 3 4 5 6 7 8 9 Unable to score Additional statements included in round 2 of the survey (for HCPs only). Strongly Neither agree Strongly disagree nor disagree agree Statement 1 2 3 4 5 6 7 8 9 Unable to score Biomarkers are useful in stratifying risk of disease progression for men undergoing active surveillance Men known to carry the BRAC2 mutation are ineligible for active surveillance ADC = apparent diffusion coefficient; BRAC2 = DNA repair associated gene; 3D-CRT= external beam radiotherapy three dimensional conformal radiotherapy; DRE = digital-rectal examination; ECOG = Eastern Cooperative Oncology Group (performance status); HCP = healthcare professional; HIFU = high intensity focussed ultrasound; IMRT = intensity modulated radiotherapy; ISUP = International Society of Urological Pathology; mpMRI = multi-parametric magnetic resonance imaging; PI-RADS = Prostate Imaging Reporting and Data System; PSA = prostate-specific antigen; TRUS = transrectal ultrasound; VMAT = Volumetric modulated arc therapy. Appendice 3: List of participants completing Rounds 1 and 2 Name Role Country of residence Monique Roobol Epidemiologist The Netherlands Gwendolyn Hooper Family and Urology nurse practitioner United States Russo Russo Nurse specialist Italy Helen Attard Bason Nurse specialist Malta Brian Corr Nurse specialist United Kingdom Foroozan Atashzadeh-Shoorideh Nursing associate professor Iran Alberto Bossi Oncologist France Maria De Santis Oncologist Germany Caroline Moore Oncologist United Kingdom Chris Parker Oncologist United Kingdom Silke Gillessen Oncologist United Kingdom, Switzerland Ronald Chen Oncologist United States Glen Kristiansen Pathologist Germany Maurizio Colecchia Pathologist Italy Arno Van Leenders Pathologist The Netherlands Murali Varma Pathologist United Kingdom Peter A. Humphrey Pathologist United States Lawrence D. True Pathologist United States Theo van der Kwast Pathologist the Netherlands, Canada Brett Cox Radiation oncologist United States Geert Villeirs Radiologist Belgium Raphaele Renard-Penna Radiologist France Olivio Donati Radiologist Switzerland Anwar Padhani Radiologist United Kingdom Francesco Giganti Radiologist United Kingdom Olivier Rouvière Radiologist France Stefano Fanti Radiologist Italy Ivo Schoots Radiologist The Netherlands Jonathan Richenberg Radiologist United Kingdom Thomas M. Pisansky Radiologist United States Tom Pickles Radiation oncologist Canada Michel Bolla Radiation oncologist France Thomas Wiegel Radiation oncologist Germany Gemma Sancho-Pardo Radiation oncologist Spain Malcolm D. Mason Radiation oncologist United Kingdom Ann Henry Radiation oncologist United Kingdom Mark Buyyounouski Radiation oncologist United States John Yaxley Urologist Australia Damien Bolton Urologist Australia Niall Davis Urologist Australia Mark Frydenberg Urologist Australia Jeremy Grummet Urologist Australia Declan Murphy Urologist Australia Shomik Sengupta Urologist Australia Philip Stricker Urologist Australia Ian Vela Urologist Australia Henry Woo Urologist Australia Laurence Klotz Urologist Canada Luke Lavallee Urologist Canada Chris Morash Urologist Canada Frederic Pouliot Urologist Canada Patrick Richard Urologist Canada Christopher Wallis Urologist Canada Sebastien Crouzet Urologist France Alexandre Ingels Urologist France Jacques Irani Urologist France Nicolas Mottet Urologist France Nikolaos Grivas Urologist Greece Michael Lardas Urologist Greece Maurizio Brausi Urologist Italy Paolo Dell'Oglio Urologist Italy Giorgio Gandaglia Urologist Italy Hiroshi Sasaki Urologist Japan Antonio Alcaraz Urologist Spain Maria J. Ribal Urologist Spain Anders Bjartell Urologist Sweden Christian Fankhauser Urologist Switzerland Tobias Gross Urologist Switzerland Yeong-Shiau PU Urologist Taiwan Roderick van den Bergh Urologist The Netherlands Max Bruins Urologist The Netherlands Peter-Paul Willemse Urologist The Netherlands Rakesh Heer Urologist United Kingdom William Cross Urologist United Kingdom James Donaldson Urologist United Kingdom Thomas B. Lam Urologist United Kingdom Matthew Liew Urologist United Kingdom Karl Pang Urologist United Kingdom Justine Royle Urologist United Kingdom Hashim U. Ahmed Urologist United Kingdom Philip Cornford Urologist United Kingdom Marcus Cumberbatch Urologist United Kingdom Alastair D. Lamb Urologist United Kingdom James Eastham Urologist United States Peter Albertsen Urologist United States Daniel A. Barocas Urologist United States Pail Crispen Urologist United States Scott Eggener Urologist United States Daniel Lin Urologist United States Steven Joniau Urologist Belgium Anil Kapoor Urologist Canada Philippe Violette Urologist Canada Derya Tilki Urologist Germany Alberto Briganti Urologist Italy Nicola Fossati Urologist Italy Piotr Chlosta Urologist Poland Chris Bangma Urologist The Netherlands Michiel Sedelaar Urologist The Netherlands Henk Van der Poel Urologist The Netherlands Konstantinos Dimitropoulos Urologist United Kingdom James N'Dow Urologist United Kingdom Stacy Loeb Urologist United States Lisa Moris Urologist in training Belgium Thomas Van den Broeck Urologist in training Belgium Urology nurse consultant & Research Catherine Paterson fellow United Kingdom Sau-loi Ng Urology specialist nurse Hong Kong Corinne Buckett Urology specialist nurse United Kingdom Karen Wilkinson Uro-oncology nurse specialist United Kingdom Patient ID Prior treatment Age Country of residence Current treatment Patient #1 No active surveillance 61-70 Belgium No Active surveillance Patient #2 Active surveillance 51-60 The Netherlands Active surveillance Patient #3 Active surveillance >70 United Kingdom No active surveillance Patient #4 No active surveillance >70 Belgium No active surveillance Patient #5 No active surveillance Belgium No active surveillance Patient #6 No Active surveillance >70 Portugal No Active surveillance Patient #7 No active surveillance 61-70 Sweden No active surveillance Patient #8 No active surveillance > 70 Switzerland No active surveillance Patient #9 Active surveillance 61-70 United Kingdom Active surveillance Patient #10 Active surveillance > 70 United Kingdom Active surveillance Patient #11 Active surveillance 61-70 United Kingdom No active surveillance Patient #12 Active surveillance > 70 United Kingdom Active surveillance Patient #13 Active surveillance 61-70 United Kingdom Active surveillance Patient #14 No active surveillance >70 United Kingdom No active surveillance Patient #15 Active surveillance >70 United Kingdom Active surveillance Patient #16 Active surveillance 51-60 United Kingdom Active surveillance Patient #17 No active surveillance >70 United Kingdom No active surveillance