GLOBAL PROSTATE CANCER OUTCOMES REGISTRY PCOR AND THE DELPHI PROJECT

Objectives Provide an overview of the registry/timeline Describe the dataset development Discuss the Delphi consensus quality indicator project Outline the next steps

PCOR- VIC PCOR- ANZ TRUENTH GLOBAL PCOR

PCOR-Vic Prostate Cancer Outcome Registry-Victoria (PCOR-VIC) Established 2009 to test feasibility of clinician-led registry to monitor quality of care 6 sites Extended to two regional areas with additional funding Currently captures 75% of cases in Victoria

PCOR-Vic

PCOR-Vic Hospital volume Positive margins Documented ct AS for low-risk disease High-risk disease having Rx Risk adjusted CaP-specific survival and recurrence PRO-sexual, bowel and urinary bother and function In-hospital death from major complications Time from biopsy to treatment for men with pt2 disease

PCOR-Vic % of men met selected QIs 100% 80% 60% 40% 20% 0% Trend in Quality Care Improvement in Victoria 2009 2010 2011 2012 2013 Year % positive surgical margins for organ-confined pathological T2 disease % of men with low-risk group who underwent prostate cancer treatment

Temporal trend - stage at diagnosis 100% 80% High risk Very high risk/ metastatic V high/ mets 6.1% to 10.5% (2011) (2016) 60% P<0.001 40% 20% Low risk Intermediate Low risk 30% to 20% (2011) (2016) 0% 2010 (n=2428) 2011 (n=2422) 2012 (n=2496) 2013 (n=2186) 2014 (n=2147) 2015 (n=2221) To 1/7/2016 (n=1033) Low Intermediate High Very high/mets

Temporal trend - Method of diagnosis 100% 80% TURP Clinical/other Transperineal 60% 40% TRUS P<0.001 20% 0% 2010 (n=2428) 2011 (n=2422) 2012 (n=2496) 2013 (n=2186) 2014 (n=2147) 2015 (n=2221) To 1/7/2016 (n=1033)

Temporal trendlow risk disease management 100% 80% AS/WW P<0.001 60% 40% EBRT BRACHY AS/WW 52% to 75% (2011) (2016) 20% SURGERY Surg 35% to 20% (2011) (2016) 0% 2010 (n=640) 2011 (n=710) 2012 (n=660) 2013 (n=529) 2014 (n=454) 2015 (n=468) To 1/7/2016 (n=208) Surg EBRT Brachy AS/WW

Temporal trendintermediate risk disease management 100% 80% EBRT EBRT 16% to 11% (2011) (2016) 60% AS/WW AS/WW 13% to 18% (2011) (2016) 40% P<0.001 20% SURGERY 0% 2010 (n=1021) 2011 (n=1016) 2012 (n=1085) 2013 (n=980) 2014 (n=961) 2015 (n=984) Surg AS/WW EBRT Surg+EBRT Brachy Other To 1/7/2016 (n=463)

Temporal trend High risk disease management (n=3245) 100% 80% ADT AS/WW ADT 15% to 8% (2011) (2016) 60% EBRT P<0.001 40% 20% SURGERY Surg 40% to 51% (2011) (2016) 0% 2010 (n=520) 2011 (n=511) 2012 (n=526) 2013 (n=459) 2014 (n=483) 2015 (n=467) To 1/7/2016 (n=220) Surg EBRT Surg+EBRT ADT AS/WW

Very high risk/ metastatic disease (n=1153) 100% OTHER 80% ADT 60% 40% CHEMO Chemo 3% to 14% (2011) (2016) 20% EBRT 0% 2010 (n=174) 2011 (n=145) 2012 (n=171) 2013 (n=157) 2014 (n=178) SURGERY 2015 (n=215) To 1/7/2016 (n=104) Surg EBRT Chemo ADT Other

PCOR-ANZ Prostate Cancer Outcome Registry-Aust and NZ Progressively rolled out National indicators developed through Delphi panel

PCOR-ANZ Data Cancer registries Mandatory hospital and pathology notifications Demographic details Diagnosing clinician/hospital Hospital databases Procedures (electronically where possible) Pathology (PSA levels)/ histopathology Consulting rooms Treatment PSA level Patients Treatment confirmation PROMs Comorbidities (no ICD complications)

TrueNTH Global Prostate Cancer Registry Prostate Cancer Outcome Registry-Global registry

TrueNTH Global Prostate Cancer Registry Largest international prostate cancer cohort study to date. It provides the ability to make a large contribution to our knowledge of how prostate cancer can best be managed to provide the best possible outcomes for men, their partners and their families.

TrueNTH Global Prostate Cancer Registry 2012: Movember funded first registry effort- PCOR-ANZ 2013: ICHOM face-to-face meeting Harvard Uni, Boston 2015: (July) PCO-CRV project EOI released for global coordination centre 2016: (May) PCO-CRV project protocol v1 for comment 2017: (Jan) PCO-CRV project commencement date 2 2013: Movember funded IPCOR- Irish Prostate Cancer initiative 2013: ICHOM localised prostate cancer minimum dataset released 2015: (Dec) PCO-CRV kick off meeting in LA. PCC/DCC led 2016: (Dec) PCO-CRV protocol released for HREC authorisation 2017: (July) PCO-CRV project data managers meeting

TrueNTH Global Prostate Cancer Registry 2012: Movember funded first registry effort- PCOR-ANZ 2013: ICHOM face-to-face meeting Harvard Uni, Boston 2015: (July) PCO-CRV project EOI released 2016: (May) PCO-CRV project protocol v1 for comment 2017: (Jan) PCO-CRV project commencement date 2 2013: Movember funded IPCOR- Irish Prostate Cancer initiative 2013: ICHOM localised prostate cancer minimum dataset released 2015: (Dec) PCO-CRV kick off meeting in LA. PCC/DCC led 2016: (Dec) PCO-CRV protocol released for HREC authorisation 2017: (July) PCO-CRV project data managers meeting

ICHOM Goals Develop consensus standardised minimum dataset Facilitate comparative effectiveness research and foster value-based healthcare, designed to engender competition between high-quality entities to achieve better outcomes for patients and simultaneously optimize cost of this care. Facilitate international collaborations to combine data, allow comparisons, insight into high value and high quality features of care, and action to adopt these more widely Mechanism to do this was not described

Study schema

The theory of positive deviance Identify organisations consistently achieving high performance in area of interest Study this organisation using qualitative methods to generate hypotheses about why this is occurring Test hypotheses in larger representative sample Disseminate evidence about newly characterised best practice

Timeline 2012: Movember funded first registry effort- PCOR-ANZ 2013: ICHOM face-to-face meeting Harvard Uni, Boston 2015: (July) PCO-CRV project EOI released 2016: (May) PCO-CRV project protocol with proposed dataset 2017: (Jan) PCO-CRV project commencement date 2 2013: Movember funded IPCOR- Irish Prostate Cancer initiative 2013: ICHOM localised prostate cancer minimum dataset released 2015: (Dec) PCO-CRV kick off meeting in LA. PCC/DCC 2016: (Dec) PCO-CRV protocol released for HREC authorisation 2017: (July) PCO-CRV project data managers meeting

Task 1: Identify participating sites and coordination centre EOI released mid-2015 for Participating Sites and Data Coordination Centre Participating Sites contribute to data governance, dataset development and evolution, analysis, dissemination of identified best practice, and monitoring change Data Coordination Centre: hosts the clinical quality registry providing high security, highly reliable, flexible controlled storage and data manipulation services Coordinates activities of the Participating Sites. Conducting principal data analyses under the guidance of the project Steering Committee

DCC and PCC appointed PCC DCC

Task 2: is ICHOM data collection feasible? Data discovery project-dcc

Task 2: is ICHOM data collection feasible?

Task 2: is ICHOM data collection feasible? Not straight away.. Concept of Tier 1 (T1) and Tier 2 (T2) introduced. By the PCO-CRV Executive Committee

G-PCOR Governance structure Global Prostate Cancer Outcomes Steering Committee Joint DCC and PCC* (Monash and UCLA) Leadership team Executive Committee PCO-CRV Project Steering Committee Czech New Australia Austria Canada Germany Ireland Italy Netherlands Spain Republic Zealand Switzerland United Kingdom USA * DCC=Global Data Coordination Centre PCC= Global Project coordination Centre

G-PCOR study sites

G-PCOR governance DCC we are all about the data and the database where it is stored We are your contact for: Any queries about data export, transfer and load Any issues with the upload Any issues with data formatting Any technical issues relating to the reports Getting access to your research data through Safe Haven PCC we are all about the project management We are your contact for: Any issues with recruitment Any requests to do with research project requests Discussion on quality improvement activities Distribution and shared of your learnings Anything to do with meetings

MODIFIED DELPHI PROCESS TO DEVELOP GLOBAL QUALITY INDICATORS

Modified Delphi panel Select a reasonable number of indicators that can measure the quality of prostate cancer management worldwide. Refine and reduce the number of quality-of-care indicators that were derived from the clinical guideline literature review. Disclaimer: We acknowledge that there are many important indicators that have not been considered in this panel discussion. Many indicators had to be excluded after the literature review due to the limitations of the PCOR-CRV dataset.

What is a Delphi panel? Delphi A process for determining consensus on something It is iterative (one round builds on the next) 3 rounds Begins with an open ended questionnaire to solicit information about a subject Often a large group participate **The modified Delphi technique is similar to the full Delphi in terms of procedure (i.e., a series of rounds with selected experts) and intent (i.e., to predict future events and to arrive at consensus). Modified Delphi Not part of the original Delphi process It is an iterative process with 3 rounds including a face-to-face meeting Begins with a set of carefully selected items for discussion Only 9-14 people participate Allows for expert interaction to provide clarification on matters and to present arguments in order to justify their point of view Studies show it is can be superior to Delphi 3,4

The Delphi panel

The Delphi process 1. Literature review 2. Feasibility with existing data 3. Online survey 1 4. Analysis of online survey 5. Face to face panel meeting 6. Online survey 2

Guidelines Ref Pub FULL REFERENCE Alberta HS 2015 Alberta Health Services Clinical Practice Guidelines for Prostate Cancer Andrology AUS 2010 Andrology Australia - Clinical Practice Guidelines for the Management of Locally Advanced and Metastatic Cancer (Australia) AUA 2013 American Urological Association - Radiotherapy after Prostatectomy (United States of America) AUA Cyrosurgery 2008 American Urological Association Best Practice Policy Statement on Cyrosurgery for the Treatment of Localised Prostate Cancer BAUS 2013 British Association of Urological Surgeons - Section of Oncology (United Kingdom) Cancer Care Ontario 2014 Cancer Care Ontario 2014 Active Surveillance for the Management of Localized Prostate Cancer (Canada) Cancer Council 2016 Cancer Council - Prostate Cancer Clinical Guidelines (Australia) EAU ED 2015 European Association of Urology - Guidelines on Male Sexual Dysfunction EAU 2017 European Association of Urology - Guidelines on Prostate Cancer (Netherlands)

Guidelines Ref Year Guideline/ Reference EAU 2017 European Association of Urology - Guidelines on Prostate Cancer (Netherlands) ESMO 2015 KCE 2014 European Society for Medical Oncology - Cancer of the Prostate: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up (Switzerland) Belgian Health Care Knowledge Centre - National Practice Guideline on the Treatment of Localized Prostate Cancer (Belgium) NCI 2016 National Cancer Institute - Prostate Cancer Treatment (United States of America) NCCN 2017 National Comprehensive Cancer Network - Clinical Practice Guidelines in Oncology: Prostate Cancer (United States of America) NCCP 2015 National Cancer Control Programme - Diagnosis, Staging and Treatment of Patients with Prostate Cancer (Ireland) NCCS 2013 National Cancer Centre Singapore - Guidelines on Management of Prostate Cancer (Singapore) NICE 2016 National Institute for Health and Care Excellence - Prostate Cancer: Diagnosis and Management (United Kingdom) NZ PCT 2013 Prostate Cancer Taskforce (New Zealand) VIC-OCP 2015 Optimal Care Pathway for Men with Prostate Cancer (Victoria, Australia)

Articles Ref (et al) Year FULL REFERENCE Ahmadi 2014 Androgen Deprivation Therapy for Prostate Cancer Patient Relat Outcome Meas., 5:63-70 Ahmed 2014 Chin 2015 Comparison of biochemical failure rates between permanent prostate brachytherapy and radical retropubic prostatectomy as a function of posttherapy PSA nadir plus X, Radiation Oncology, 9:171 Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation or Prostate Tissue in Patients with Localized Prostate Cancer: A Prospective Phase 1 Clinical trial, European Urology, 70:447-455 Loeb 2013 Systematic review of complications of prostate biopsy Eur.Urol., 64 (6), pp. 876 892 Nag 2016 Development of Indicators to Assess Quality of Care for Prostate Cancer. Eur Urol Focus Punnen 2015 Ramsay 2015 Long-Term Health-Related Quality of Life after Primary Treatment for Localized Prostate Cancer: Results from the CaPSURE Registry, European Urology, 68(4):600-608 Ablative therapy for People with Localized Prostate Cancer: A Systematic Review and Economic Evaluation - Chapter 4: The Comparative Effectiveness of Cryotherapy, Health Technology Assessment, No. 19.49 Resnick 2013 Long-Term Functional Outcomes after Treatment for Localized Prostate Cancer, N Engl J Med Jan 31;368(5):436-45 Robinson 2009 A Randomized Trial of External Beam Radiotherapy versus Cryoblation in Patients with Localized Prostate Cancer Quality of Life Outcomes, Cancer, 115 (20) Wegner 2014 Laser Ablation as Focal Therapy for Prostate Cancer, Curr Opin Uro, 24(3):236-240 Yap 2016 The Effects of Focal Therapy for Prostate Cancer on Sexual Function: A Combined Analysis of Three Prospective Trials, European Urology, 69(5):844-851

The Delphi process 1. Literature review 2. Feasibility with existing data 3. Online survey 1 4. Analysis of online survey 5. Face to face panel meeting 6. Online survey 2

Which indicators to include 1. Those where there is a high level of agreement among the panel that it is a good indicator = Median score 2. Those where there is little disagreement (dispersion) among the panel that it is a good indicator = Disagreement Index (DI)

The Delphi process Median score 7-9 and no disagreement (DI<1) Any disagreement regardless of median score (DI 1) Median score 1-6 and no disagreement

The Delphi process Panellist ID #1 #2 #3 #4 #5 #6 #7 #8 #9 #10 #11 Rating given (from 1-9) 1 2 3 5 5 5 5 5 7 8 9 Median: 5 Lower IPR: 10 th percentile = 2 Upper IPR: 90 th percentile = 8 IPR: 8-2 = 6 IPRCP: (2+8) / 2 = 5 Asymmetry index: 5-5 = 0 IPRAS: 2.35 + (1.5 x 0) = 2.35 Disagreement Index (DI): 6 / 2.35 = 2.55

The Delphi process Panellist ID #11 #12 #13 #14 #15 #16 #17 #18 #19 #20 #21 Rating given (from 1-9) 1 1 7 8 9 7 8 9 7 8 9 Median: 8 Lower IPR: 10 th percentile = 1 Upper IPR: 90 th percentile = 9 IPR: 9-1 = 8 IPRCP: (1+9) / 2 = 5 Asymmetry index: 5-5 = 0 IPRAS: 2.35 + (1.5 x 0) = 2.35 Disagreement Index (DI): 8 / 2.35 = 3.40

The Delphi process Panellist ID #11 #12 #13 #14 #15 #16 #17 #18 #19 #20 #21 Rating given (from 1-9) 3 4 4 5 5 5 5 5 6 6 7 Median: 5 Lower IPR: 10 th percentile = 4 Upper IPR: 90 th percentile = 6 IPR: 6-4 = 2 IPRCP: (4+6) / 2 = 5 Asymmetry index: 5-5 = 0 IPRAS: 2.35 + (1.5 x 0) = 2.35 Disagreement Index (DI): 2 / 2.35 = 0.85

The Delphi process 1. Literature review 2. Feasibility with existing data 3. Online survey 1 4. Analysis of online survey 5. Face to face meeting 6. Online survey 2 This means that the Median panel score (scale 1-9) was 9 and the Disagreement Index was 0.37

Results from round 1 Arghhh!!!!!

The Delphi process 1. Literature review 2. Feasibility with existing data 3. Online survey 1 4. Analysis of online survey 5. Face to face panel meeting 6. Online survey 2

Vancouver

The Delphi process Face to face meeting Rated importance AND feasibility (scale 1-9)

The Delphi process

Quality indicators # Indicator Diag Initial investigations of a male with PCa include measurement of PSA level Diag T category/stage (DRE or MRI) is documented prior to treatment for localised PCa Diag In men with high risk localised PCa, nodal staging using CT, MRI or PET/CT is performed Diag In men with high risk localised PCa, perform metastatic screening using a CT/MRI and a bone scan Diag In men with intermediate risk localised PCa, a bone scan is not conducted

Quality indicators # Indicator Diag Diag Primary Rx Primary Rx Primary Rx Primary Rx In men with low risk PCa, a bone scan is not conducted In men with low risk localised PCa, a CT is not conducted Men with high risk localised PCa receive active treatment Men with high risk localised PCa do not receive AS PSA is taken within 3 months post RP For pn0 men undergoing RP, adjuvant ADT is not given

Quality indicators # Indicator Men with localised PCa who are undergoing radical EBRT receive a Primary Rx Primary Rx Primary Rx Primary Rx Salvage Rx Outcome minimum dose of 74Gy at standard fractionation or the equivalent of hypofractionation to the prostate PSA level is taken within 12 months post RT Men with high risk localised PCa do not receive brachytherapy alone PSA level is taken within 6 months post focal therapy Men who have salvage RT post RP receive a salvage RT dose 66 Gy at standard fractionation or the equivalent hypo-fractionated dose EPIC-26 is completed 12 months post diagnosis for men on AS and 12 months post active treatment for men receiving active treatment

Quality indicators # Indicator Outcome Outcome Outcome Outcome Outcome Outcome EPIC-26 is completed at baseline EORTC QLQ-PR25 is completed 12 months post diagnosis for men on AS and 12 months post active treatment for men receiving active treatment Utilisation of Sexual Medication/Devices is completed 12 months post diagnosis for men on AS and 12 months post active treatment for men receiving active treatment EORTC QLQ-PR25 is completed at baseline Utilisation of Sexual Medication/Devices is completed at baseline Death within 30 days of RP

Quality indicators # Indicator Outcome Outcome Men with low risk PCa who had a positive margin post-rp Men with pt2 disease who had a positive margin post-rp Outcome Men with pt3 disease who had a positive margin post-rp Outcome Biochemical recurrence at 1 year post RP Outcome Radical or systemic treatment at 18 months post focal-gland or whole-gland ablation therapy

Next steps 1. Publish findings 2. Build the reports 3. Test and refine the indicators 4. Develop reports 5. Distribute reports to LDCs 6. LDCs will distribute reports to participating sites

Building the reports

Acknowledgement PCO-CRV Monash/Movember team Fanny Sampurno Jeremy Millar Jia Zheng Ellie James Ashwini Kannon Harvey Goh PCO-CRV UCLA team Sarah Connor Delphi panel Mark Litwin Emily Pearman TrueNTH Steering Committee Contributors to the registry PCOR-Vic and ANZ team Melanie Evans Gabriella Tikellis Data collector and follow up team

Acknowledgement Funding bodies Thank you PCOR-Vic Steering Committee Contributing clinicians and hospitals Participating men PCOR-Vic data collectors and researchers Endorsing groups

Questions?