MedPath

International REgistry of COnservative or Radical Treatment of Localized Kidney Tumors

Recruiting
Conditions
Kidney Cancer
Interventions
Procedure: Partial Nephrectomy (PN)
Procedure: Radical Nephrectomy (RN)
Procedure: Ablation therapy (AT)
Diagnostic Test: Active Surveillance (AS)
Registration Number
NCT05363657
Lead Sponsor
Azienda Ospedaliero-Universitaria Careggi
Brief Summary

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).

Detailed Description

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
10000
Inclusion Criteria
  • Radiological diagnosis of renal tumor susceptible to active treatment or AS/WW.
  • Age ≥18 years
  • Informed consent signed
Exclusion Criteria
  • Patient refuse to participate in clinical research.
  • Urothelial renal carcinoma.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Renal tumor patiensAblation therapy (AT)Patients with any renal tumor diagnosed with conventional imaging (computed tomography or magnetic resonance imaging) and undergoing to a clinical management in a hugh-volume center.
Renal tumor patiensActive Surveillance (AS)Patients with any renal tumor diagnosed with conventional imaging (computed tomography or magnetic resonance imaging) and undergoing to a clinical management in a hugh-volume center.
Renal tumor patiensPartial Nephrectomy (PN)Patients with any renal tumor diagnosed with conventional imaging (computed tomography or magnetic resonance imaging) and undergoing to a clinical management in a hugh-volume center.
Renal tumor patiensRadical Nephrectomy (RN)Patients with any renal tumor diagnosed with conventional imaging (computed tomography or magnetic resonance imaging) and undergoing to a clinical management in a hugh-volume center.
Primary Outcome Measures
NameTimeMethod
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.Assesment of the "Trifecta" outcome will be performed at 12 months from the surgical intervention. Time frame: 1 year.

"Trifecta" rate is defined as 1) Absence of intraoperative and postoperative surgical complications; 2) absence of positive surgical margins or recurrences on tumor resection site during a 5-year follow-up; 3) Absence of clinically significant renal function loss at one year after surgery. Renal function will be evaluated using the estimated glomerular filtration rate (eGFR) in ml/min/1.73 m\^2 using the CKD-EPI Creatinine Equation (2021). A clinically significant loss will be considered if \>25% from eGFR at baseline.

The "Trifecta" outcome will be evaluated one year from surgery.

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?Assesments of the outcome at 60 months from the surgical intervention. Time frame : 5 years

The preoperative characteristics of the patients will be specifically evaluated to calculate any heterogeneity between the two groups. In detail, anthropometric and comorbidity features, previous abdominal surgery, blood chemistry values, blood pressure, smoking habit, preoperative life expectancy, and frailty grade will be assessed. Imaging features of the tumor will be considered, including the characteristics necessary for the calculation of the PADUA, R.E.N.A.L., and Contact-Surface-Area scores. Patients with a node-positive or metastatic disease diagnosed with conventional imaging (CT scan/MRI) will be excluded. Intra-operative and post-operative outcomes will be evaluated. Histopathological features of the tumor will be assessed.

Patients will be followed up with conventional imaging according to the International guidelines (ultrasound, CT, MRI). Serum creatinine, platelets and estimated glomerular function (eGFR), the onset of cardiovascular adverse events will be registered.

Secondary Outcome Measures
NameTimeMethod
To evaluate the impact of the antiaggregant and/or antiplatelet treatment at baseline and during partial nephrectomy on hemorrhagic complications.Outcome assesment will be done at 90 days from surgery. Time frame: 3 months

The eventual anticoagulant therapy (heparin, warfarin, enoxaparin, fondaparinux) and/or antiplatelet therapy (clopidogrel, ticagrelor, prasugrel, dipyridamole, dipyridamole/aspirin, ticlopidine, eptifibatide) use in patients at baseline and at time of surgery will be assessed.

Hemorrhagic complications (graded according to the "Clavien-Dindo classification") will be evaluated during surgery (intraoperative) and within 90 days (postoperative) with particular attention to the management of hemorrhage (patient monitoring, transfusion, selective embolization, re-intervention with/without kidney removal).

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.Assesment will be done at the time of registering the type of surgery/clinical managing adopted. Time frame: <1 week from patients accrual..

The following variables will be evaluated:

1. Anthropometric, pre-operative and comorbidity data (patient characteristics).

2. Imaging data and pre-operative tumor features (tumor characteristics).

3. Centre facilities (laparoscopic/robot assisted, interventional radiology) , volume centre (PN/RN ratio, availability of Multidisciplinary Tumor Board)

4. Intra-operative and post-operative data (treatment characteristics).

5. Histopathological analysis (tumor histopathological characteristics). The outcome will be considered as the type of clinical management selected: active surveillance (AS) vs ablative treatment (AT) vs partial nephrectomy (PN) vs radical nephrectomy (RN).

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.Outcome assesment will be done at 90 days from surgery. Time frame: 3 months

The eventual anticoagulant therapy (heparin, warfarin, NAO, enoxaparin, fondaparinux) and/or antiplatelet therapy (clopidogrel, ticagrelor, prasugrel, dipyridamole, dipyridamole/aspirin, ticlopidine, eptifibatide) use in patients at baseline and at time of surgery will be assessed.

Change of treatment from baseline to time of surgery will be considered and specifically evaluated according to the underlying cardio- and/or peripheral- and/or cerebro-vascular diseases.

Trial Locations

Locations (37)

Humanitas Hospital

🇮🇹

Rozzano, Italy

Amsterdam University Medical Centers

🇳🇱

Amsterdam, Netherlands

European Health Center

🇵🇱

Otwock, Poland

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie

🇵🇱

Warsaw, Poland

Fundaciò Puigvert

🇪🇸

Barcelona, Spain

NG Teng Fong General Hospital

🇸🇬

Singapore, Singapore

Bristol Urological Institute

🇬🇧

Bristol, United Kingdom

University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Policlinico Riuniti, Università di Foggia.

🇮🇹

Foggia, Italy

Division of Urology, University of Genoa,Policlinico San Martino Hospital

🇮🇹

Genova, Italy

Azienda Ospedaliera Policlinico "G. Martino", Università di Messina.

🇮🇹

Messina, Italy

San Raffaele Scientific Institute, Milan, Italy; Division of Experimental Oncology/Unit of Urology, URI, IRCCS San Raffaele Hospital

🇮🇹

Milano, Italy

Istituto Nazionale dei Tumori Fondazione Senatore "G. Pascale"

🇮🇹

Napoli, Italy

Institute Oncology Veneto (IOV)

🇮🇹

Padova, Italy

Università degli studi di Torino, Ospedale Molinette

🇮🇹

Torino, Italy

University of Bruxelles

🇧🇪

Bruxelles, Belgium

Onze Lieve Vrouw Hospital

🇧🇪

Leuven, Belgium

Loyola University Medical Center, Edward Hines VA Hospital

🇺🇸

Chicago, Illinois, United States

Stanford University

🇺🇸

Stanford, California, United States

Medical University of Vienna, Vienna General Hospital

🇦🇹

Vienna, Austria

Urology, Andrology & Kidney Transplantation Unit, University of Bari

🇮🇹

Bari, Italy

Santa Casa da Misericórdia de Fortaleza

🇧🇷

Fortaleza, Brazil

Policlinico S. Orsola Malpighi

🇮🇹

Bologna, Italy

Department of Urology, University of Florence, Unit of Oncologic Minimally-Invasive Urology and Andrology, Careggi Hospital

🇮🇹

Firenze, Italy

Policlinico Istituto Europeo di Oncologia (IEO)

🇮🇹

Milano, Italy

Università degli Studi di Torino, Ospedale S. Luigi Gonzaga.

🇮🇹

Torino, Italy

AOUI Verona

🇮🇹

Verona, Italy

Jikei University School of Medicine

🇯🇵

Tokyo, Japan

Hospital Universitario Ramón y Cajal, University of Alcalá

🇪🇸

Madrid, Spain

Institute of Urology, University of Southern California.

🇺🇸

Los Angeles, California, United States

VCU Health System

🇺🇸

Richmond, Virginia, United States

Swedish Hospital

🇺🇸

Seattle, Washington, United States

University of California San Diego, Moores Cancer Center

🇺🇸

San Diego, California, United States

University Hospitals Leuven

🇧🇪

Leuven, Belgium

University of Patras

🇬🇷

Patras, Greece

N.N. Blokhin National Medical Research Center of Oncology

🇷🇺

Moscow, Russian Federation

Guy's Hospital

🇬🇧

London, United Kingdom

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