John Fitzpatrick Memorial Lecture. John Fitzpatrick Memorial lecture

John Fitzpatrick Memorial Lecture

John Fitzpatrick Memorial Lecture John M Fitzpatrick, 1948 2014 Head of Research at the Irish Cancer Society Professor of Surgery and Consultant Urologist at the Mater Misericordiae University Hospital and University College Dublin School of Medicine & Medical Science Editor-in-Chief of the British Journal of Urology Int President of the Irish Society of Urology President of the British Association of Urological Surgeons

Development of Guidelines in a Rapidly Changing Treatment Landscape Börje Ljungberg Professor of Urology, Department of Surgical and perioperative sciences, Umeå University Sweden John Fitzpatrick Memorial Lecture

Disclosures Advisory Boards: Ipsen, Novartis Lectures; Pfizer; GSK, Astellas,

RCC Guidelines A cookery book - for clinicians or Guidance for the informed care decisions of the patients

Development of Guidelines Guidelines Clinical expert EAU RCC Guidelines - first published in 2000

Development of Guidelines I figure there s a 40 % chance of showers, and a 10 % chance we know what we re talking about.

EAU RCC Guidelines - constructed to advise urologists in their clinical work - to address key questions of clinical relevance - using transparent production process and continuous updating - strive to improve the quality of the evidence through research suggestions

Development of Guidelines in a Rapidly Changing Treatment Landscape, Rapid Shifts in: Literature Search Strategy Treatment Options Technical Improvements - imaging - it - molecular evaluation Recommendations Stakeholder Participation Communication social media - Web John Fitzpatrick Memorial Lecture

RCC Guidelines Literature Search Strategy Discursive didactic texts often reflecting the experience of the authors and their known literature Narrative literature search Traditional narrative review, based on a structured literature assessment. Systematic literature search, based on structured assessment In the 2016 search wwe used Systematic Reviews [SRs] with metaanalysis, Randomized Controlled Trials (RCTs), and prospective nonrandomised comparative studies, - 2333 abstracts screened out of 10348

PICO s Patient or population Intervention, (what to do) Comparision Outcome questions in therapy, diagnosis, etiology

Flow Diagram form PICO : Role of local treatment in metastatic RCC 1763 abstracts identified 88 Full text screening 73 excluded 15 studies included Ljungberg Madrid 2015

des of Recommendation A B C D Grades of Recommendation consistent level 1 studies consistent level 2 or 3 studies or extrapolations from level 1 studies level 4 studies or extrapolations from level 2 or 3 studies level 5 evidence or troublingly inconsistent or inconclusive studies of any level

modified GRADE methodology Grading of Recommendations Assessment, Development and Evaluation The recommendation address a number of key elements: the overall quality of the evidence the magnitude of the effect the certainty of the results the balance between desirable and undesirable outcomes the impact of patient values and preferences on the intervention the certainty of those patient values and preferences

Example of modified GRADE approach Results from a meta-analysis of ASSURE and STRAC trials show statistically non-significant results for DFS (combined HR 0.89, 95% CI 0.67 1.19) Bex A, Updated European Association of Urology Guidelines Regarding Adjuvant Therapy for Renal Cell Carcinoma. Eur Urol. 2017

RCC Panel members voted which results from the S-TRAC study that would change their standard practice

Recommendation of the EAU RCC Guidelines Panel Recommendation Strength Adjuvant sunitinib following surgically Weak resected high-risk clear-cell renal cell carcinoma is not recommended

Guidelines in a Rapidly Changing Treatment Landscape Diagnostic - Imaging - Histology/ Molecular Surgical treatment - Surgical strategy - Minimal invasive techniques Systemic therapy - targeting agents - immunotherapy Radiation treatment Molecular treatment

Evidence levels in Surgical Treatmentof RCC The level of evidence - in general low Expert opinions or parachute evidence Few RCT Few comparative studies New technical improvements introduced without RTCs

Partial nephrectomy surgery vs minimal invasive treatments Cryo or RF Comparing open, laparoscopic or robotic PN vs. cryoablation. Oncological outcomes were mixed, most showing significant benefit for PN No study showed oncological benefit for Cryo over PN. One study compared PN with ablation therapy, either Cryo or RFA, and showed significantly improved DSS at both 5 and 10 years for PN

RPN vs LPN - No studies compared oncological outcomes! - A comparison of surgical outcomes in moderate-complex renal tumours showed: lower blood loss, shorter warm ischaemia time for RPN - Two meta-analyses of relatively small series showed comparable peri-operative outcomes and a shorter warm ischaemia time for RPN

Tumor Thrombus Surgery Low quality data suggest that tumour thrombus in nonmetastatic disease should be excised. LE 3 Recommendations In patients with non-metastatic RCC, excise the kidney tumour and the vena cava thrombus. GRADE strong

Topics of ongoing SRs on treatment The results of updated and new SRs to be included in update 2018 What is the best treatment option for T1-T2 tumors? - updated review What is the best treatment option for T1a tumors? What is the best treatment option for T1b-T2a tumors? - updated review What is the best treatment option for T2b tumors? Systematic review and meta-analysis of systemic therapy (Cochrane Review)

Evidence levels in RCC Systemic Treatment The level of evidence - in general high A number of RCTs

mrcc - Treatment options Targeted therapy TKI mtor PD-1 inhibition Cytokine (IL-2, IFN-alpha) vaccins 27

EAU Guidelines Recommendations for patients with mccrcc who have failed one or more lines of VEGF targeted therapy Ljungberg Madrid 2015

Follow-up No consensus on surveillance strategy No evidence that early vs. later diagnosis of recurrences improves survival Follow-up is important to increase the available information on RCC after treatment improve the quality of the evidence through research suggestions A multicenter study of FU is initiated with a base in the RCC Guidelines panel (Debastini, Bex et al. ) Aim to improve the quality of the evidence

RCC panel improve the quality of the evidence through research, 2016-2017 publications 1. MacLennan SJ. Changing Current Practice in Urology: Improving Guideline Development and Implementation Through Stakeholder Engagement. Eur Urol. 2017. 2. Bex A. Updated European Association of Urology Guidelines Regarding Adjuvant Therapy for Renal Cell Carcinoma. Eur Urol. 2017. 3. Fernández-Pello S. A Systematic Review and Meta-analysis Comparing the Effectiveness and Adverse Effects of Different Systemic Treatments for Non-clear Cell Renal Cell Carcinoma. Eur Urol. 2017 4. Bex A. The Role of Cytoreductive Nephrectomy: European Association of Urology Recommendations in 2016. Eur Urol. 2016 5. Powles T. European Association of Urology Guidelines for Clear Cell Renal Cancers That are Resistant to Vascular Endothelial Growth Factor Receptor-Targeted Therapy. Eur Urol. 2016 6. Marconi L, et al. Systematic Review and Meta-analysis of Diagnostic Accuracy of Percutaneous Renal Tumour Biopsy. Eur Urol 2016 7. Marconi L. Letter to the Editor. Eur Urol. 2016 8: Lardas M. Systematic Review of Surgical Management of Nonmetastatic Renal Cell Carcinoma with Vena Caval Thrombus. Eur Urol. 2016. 9. Bex A, Ljungberg B. Comparing Everolimus to Sunitinib in Non-clear-cell Renal Cell Carcinoma. Eur Urol. 2016 10. Powles T. Updated EAU Guidelines for Clear Cell Renal Cancer Patients Who Fail VEGF Targeted Therapy. Eur Urol. 2016.

Development of Guidelines Guidelines Clinical expert

Development of Guidelines Guidelines Clinical expert health care organisatons, policy makers, funding bodies

Processing guidelines Propose topics Prioritize PICO Choose outcomes Systematic review Evidence grading Recommendation (Grade) Publish guidance Update

Conclusions - in Development of Guidelines in a Rapidly Changing Treatment Landscape Ensure that available clinical evidence is identified in a structured unbiased fashion Ensure that significant data is not missed The need to frequently update guidelines documents Identify gaps in the literature Prioritize future systematic Review activities

Acknowledgements RCC Guidelines panel members RCC GO members Karin Plass Umeå University Research Nurses Staff and Colleagues Lab associates

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