International REgistry of COnservative or Radical Treatment of Localized Kidney Tumors

Официальное название

International REgistry of COnservative or Radical Treatment of Localized Kidney Tumors (i-RECORd)

Обзор

Partial nephrectomy (PN) is the standard treatment for localized renal masses and should be preferred in clinical T1 (\<7 cm tumor diameter) renal tumors over radical nephrectomy (RN) whenever technically feasible. Nonetheless, indications, approaches, techniques for PN, and correct reporting of outcomes, are still a matter of great debate within the urology community. Concurrently, case-report series suggested that alternative strategies for the treatment of localized renal tumors (ablation techniques (AT), watchful waiting (WW), active surveillance (AS)) could be feasible with acceptable oncologic outcomes in particular settings of patients with localized renal tumors. In this complex clinical scenario, the role surgeon-related and environmental factors (such as surgical experience, hospital resources, countries' social background and performance of health system) are important to address the best personalized approach in patients with renal tumors. In the light of current evidence, many unsolved questions still remain and many unmet needs must be addressed. In particular, 1) the risk-benefit trade-offs between PN and RN for anatomically complex renal localized tumors; 2) the definition of evidence-based strategies to tailor the management strategy (AT vs WW vs AS vs surgery) in different subset of patients with particular clinical conditions (i.e. old, frail, comorbid patients); and 3) the definition of evidence-based recommendations to adapt surgical approach (open vs laparoscopic vs robotic) and resection techniques to different patient-, tumor-, and surgeon-specific characteristics. To meet the challenges, to overcome the limitations of current kidney cancer literature (such as the retrospective study design, potential risk of biases, and heterogeneous follow-up of most series), and to provide high-quality evidence for future development of effective clinical practice Guidelines, we designed the international REgistry of COnservative or Radical treatment of localized kiDney tumors (i-RECORD) Project. The expected impact of the i-RECORD project is to provide robust evidence on the leading clinical and environmental factors driving selection of the management strategy in patients with kidney cancer, and the differential impact of different management strategies (including AS, WW, AT, PN and RN) on functional, perioperative and oncological outcomes, as well as quality of life assessment, at a mid-long term follow-up (5-10 years).

Подробное описание

Study design

The overall objective of the i-RECORD project is to build a multicentre multi-arm multi-stage prospective observational registry collecting data on the management of kidney cancer in consecutive patients treated at 50 tertiary referral Centers worldwide over a 2 years-period and with 5 years of follow-up

. On this registry, six prospective trials with specific objectives have been built.

The i-RECORd project is designed as an observational prospective longitudinal trial involving 50 international, very-high-volume tertiary referral Centers with extensive experience in management of kidney cancer. Centers will be included in the project only if they will be able to certify at least to: 1) perform 150 partial and radical nephrectomy/year, or 2) to perform 80 ATs/year, or 3) to include 50 patients in WW/AS protocols/year.

The enrollment and follow-up periods will be 2 and 5 years, respectively. The estimate of patients' enrollment over the study period is 10'000 inclusions.

The 50 Centers finally enrolled in the i-RECORD project will be given the access to a web-based platform for data collection for 24 months from the starting date of the project.

A web-based e-form platform will be used for data collection.

Data collection

This observational study aims to obtain controlled, qualitative and quantitative, data of the enrolled patients through a web-based e-form platform. For all patients it will be asked to complete a data collection form specifically designed for this study, consisting of some subfolders:

1. Anthropometric, pre-operative and comorbidity data (patient characteristics). 2. Imaging data e and pre-operative tumor features (tumor characteristics). 3. Intra-operative and post-operative data (treatment characteristics). 4. Histopathological analysis (tumor histopathological characteristics). 5. Patients follow-up variables (at 6, 12, 24 and 60 months from the treatment) (follow-up characteristics).

Decision Analysis Modeling

Beyond traditional descriptive and inferential statistical analyses, the i-RECORd project will provide a comprehensive overview of the current selection criteria for each type of management option by applying innovative statistical methods (Decision Analysis Modeling through discrete choice models) to determine the differential impact of all potential relevant variables on the choice of treatment. To do so, we will consider specific clinical scenarios (clinical clusters) made of the integration of patient characteristics (comorbidity score, performance status, age, gender, etc.), patient-reported outcomes measures (PROMs), tumors anatomical features (degree of complexity, clinical diameter, side, location within the kidney, involvement of renal sinus or collecting system, etc.), surgeon-related factors (surgical experience and background), hospital economic availabilities (i.e. open, laparoscopic, robotic surgery) and other country-specific socio-economical features in order to determine the impact of such variables on the final choice of treatment.

By applying the discrete choice model to the analysis of the prospective dataset, the i-RECORd project will overcome the current state of the art in the treatment of localized renal tumors as it will show how the choice of treatment is performed by the decision-maker (at a surgeon- and hospital-level) in each specific clinical cluster of patients, why that choice was performed according to a careful analysis of the personalized patient setting and whether that choice will influence the postoperative outcomes.

Adapted MAMS Registry

The i-RECORD will be designed adapting the innovative concept of multi-arm, multi-stage (MAMS) platform randomized trials (used, for instance, for the design of the Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) Trial) to create a dynamic, observational registry evaluating simultaneously different management options in different patient- and/or tumor-related scenarios.

Вмешательства

• Процедура Partial Nephrectomy (PN)
  Conservative removal of kidney tumor. The procedure can be performed either with an open or laparoscopic or robotic approach.
• Процедура Radical Nephrectomy (RN)
  Surgical removal of the affected kidney. Adrenal removal can be performed according to surgeon choice and clinical characteristics of the renal tumor. The procedure can be performed either with an open or laparoscopic or robotic approach.
• Процедура Ablation therapy (AT)
  The procedure of tumor ablation performed with radiofrequency or cryoablation. The procedure can be performed either with a laparoscopic approach or percutaneous access.
• Диагностический тест Active Surveillance (AS)
  Active surveillance is defined as the initial management including the monitoring of renal tumor size by serial imaging with delayed treatment in case of progression.

Первичные конечные точки

• To test the effectiveness of partial nephrectomy for the treatment of localized renal tumors (T1-T2N0M0) with regards to recurrence-free survival and cardiovascular accidents and mortality in comparison to radical nephrectomy? [Срок оценки: Assesments of the outcome at 60 months from the surgical intervention. Time frame : 5 years]
• To test the effectiveness of robotic approach in partial nephrectomy to increase the "Trifecta" rate after nephron-sparing surgery in patients with T1-T2N0M0 renal tumors. [Срок оценки: Assesment of the "Trifecta" outcome will be performed at 12 months from the surgical intervention. Time frame: 1 year.]

Вторичные конечные точки (3)

• To evaluate the differential impact of patients' comorbidities, tumors' complexity, surgeons' experience, country-related socio-cultural factors and hospital financial resources on the selection of the type of clinical management. [Срок оценки: Assesment will be done at the time of registering the type of surgery/clinical managing adopted. Time frame: <1 week from patients accrual..]
• To evaluate the impact of the antiaggregant and/or antiplatelet treatment at baseline and during partial nephrectomy on hemorrhagic complications. [Срок оценки: Outcome assesment will be done at 90 days from surgery. Time frame: 3 months]
• To assess in patients with antiaggregant and/or antiplatelet treatment at baseline any potential change of this therapy at the time of treatment associated with the absence of hemorrhagic complications. [Срок оценки: Outcome assesment will be done at 90 days from surgery. Time frame: 3 months]

Критерии участия

Критерии включения

• Radiological diagnosis of renal tumor susceptible to active treatment or AS/WW.
• Age ≥18 years
• Informed consent signed

Критерии исключения

• Patient refuse to participate in clinical research.
• Urothelial renal carcinoma.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Италия · 14 центров

• Urology, Andrology & Kidney Transplantation Unit, University of Bari — Bari
• Policlinico S. Orsola Malpighi — Bologna
• Department of Urology, University of Florence, Unit of Oncologic Minimally-Invasive Urolog — Florence
• Policlinico Riuniti, Università di Foggia. — Foggia
• Division of Urology, University of Genoa,Policlinico San Martino Hospital — Genova
• Azienda Ospedaliera Policlinico "G. Martino", Università di Messina. — Messina
• San Raffaele Scientific Institute, Milan, Italy; Division of Experimental Oncology/Unit of — Milan
• Policlinico Istituto Europeo di Oncologia (IEO) — Milan
• … и ещё 6 центров

США · 7 центров

• Institute of Urology, University of Southern California. — Los Angeles
• University of California San Diego, Moores Cancer Center — San Diego
• Stanford University — Stanford
• Loyola University Medical Center, Edward Hines VA Hospital — Chicago
• University of Pennsylvania — Philadelphia
• VCU Health System — Richmond
• Swedish Hospital — Seattle

Бельгия · 3 центра

• University of Bruxelles — Brussels
• University Hospitals Leuven — Leuven
• Onze Lieve Vrouw Hospital — Leuven

Польша · 2 центра

• European Health Center — Otwock
• Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie — Warsaw

Испания · 2 центра

• Fundaciò Puigvert — Barcelona
• Hospital Universitario Ramón y Cajal, University of Alcalá — Madrid

Великобритания · 2 центра

• Bristol Urological Institute — Bristol
• Guy's Hospital — London

Австрия · 1 центр

• Medical University of Vienna, Vienna General Hospital — Vienna

Бразилия · 1 центр

• Santa Casa da Misericórdia de Fortaleza — Fortaleza

Греция · 1 центр

• University of Patras — Pátrai

Япония · 1 центр

• Jikei University School of Medicine — Tokyo

Нидерланды · 1 центр

• Amsterdam University Medical Centers — Amsterdam

Россия · 1 центр

• N.N. Blokhin National Medical Research Center of Oncology — Moscow

Сингапур · 1 центр

• NG Teng Fong General Hospital — Singapore

Публикации

• Ljungberg B, Bensalah K, Canfield S, Dabestani S, Hofmann F, Hora M, Kuczyk MA, Lam T, Marconi L, Merseburger AS, Mulders P, Powles T, Staehler M, Volpe A, Bex A. EAU guidelines on renal cell carcinoma: 2014 update. Eur Urol. 2015 May;67(5):913-24. doi: 10.1016/j.eururo.2015.01.005. Epub 2015 Jan 21. PMID 25616710
• Global Burden of Disease Cancer Collaboration; Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, Brenner H, Dicker DJ, Chimed-Orchir O, Dandona R, Dandona L, Fleming T, Forouzanfar MH, Hancock J, Hay RJ, Hunter-Merrill R, Huynh C, Hosgood HD, Johnson CO, Jonas JB, Khubchandani J, Kumar GA, Kutz M, Lan Q, Larson HJ, Liang X, Lim SS, Lopez AD, MacIntyre MF, Marczak L, Marquez N, Mokdad AH, PMID 27918777
• Campbell S, Uzzo RG, Allaf ME, Bass EB, Cadeddu JA, Chang A, Clark PE, Davis BJ, Derweesh IH, Giambarresi L, Gervais DA, Hu SL, Lane BR, Leibovich BC, Pierorazio PM. Renal Mass and Localized Renal Cancer: AUA Guideline. J Urol. 2017 Sep;198(3):520-529. doi: 10.1016/j.juro.2017.04.100. Epub 2017 May 4. PMID 28479239
• Stewart SB, Thompson RH, Psutka SP, Cheville JC, Lohse CM, Boorjian SA, Leibovich BC. Evaluation of the National Comprehensive Cancer Network and American Urological Association renal cell carcinoma surveillance guidelines. J Clin Oncol. 2014 Dec 20;32(36):4059-65. doi: 10.1200/JCO.2014.56.5416. Epub 2014 Nov 17. PMID 25403213
• Motzer RJ, Jonasch E, Agarwal N, Bhayani S, Bro WP, Chang SS, Choueiri TK, Costello BA, Derweesh IH, Fishman M, Gallagher TH, Gore JL, Hancock SL, Harrison MR, Kim W, Kyriakopoulos C, LaGrange C, Lam ET, Lau C, Michaelson MD, Olencki T, Pierorazio PM, Plimack ER, Redman BG, Shuch B, Somer B, Sonpavde G, Sosman J, Dwyer M, Kumar R. Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in PMID 28596261
• Volpe A, Blute ML, Ficarra V, Gill IS, Kutikov A, Porpiglia F, Rogers C, Touijer KA, Van Poppel H, Thompson RH. Renal Ischemia and Function After Partial Nephrectomy: A Collaborative Review of the Literature. Eur Urol. 2015 Jul;68(1):61-74. doi: 10.1016/j.eururo.2015.01.025. Epub 2015 Feb 20. PMID 25703575
• Finelli A, Ismaila N, Bro B, Durack J, Eggener S, Evans A, Gill I, Graham D, Huang W, Jewett MA, Latcha S, Lowrance W, Rosner M, Shayegan B, Thompson RH, Uzzo R, Russo P. Management of Small Renal Masses: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2017 Feb 20;35(6):668-680. doi: 10.1200/JCO.2016.69.9645. Epub 2017 Jan 17. PMID 28095147
• Larcher A, Sun M, Dell'Oglio P, Trudeau V, Boehm K, Schiffmann J, Tian Z, Fossati N, Capitanio U, Briganti A, Montorsi F, Karakiewicz P. Mortality, morbidity and healthcare expenditures after local tumour ablation or partial nephrectomy for T1A kidney cancer. Eur J Surg Oncol. 2017 Apr;43(4):815-822. doi: 10.1016/j.ejso.2016.08.023. Epub 2016 Sep 17. PMID 27692535

Идентификаторы

NCT: NCT05363657 · i-RECORd

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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