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

Sponsor

Azienda Ospedaliero-Universitaria Careggi (Other)

Overall Status

Recruiting

CT.gov ID

NCT05363657

Collaborator

Società Italiana di Urologia (SIU) (Other), Italian Group for Advanced Laparo-Endoscopic and Robotic Urologic Surgery (AGILE) (Other)

10,000

Enrollment

Locations

83.7

Anticipated Duration (Months)

270.3

Patients Per Site

3.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Kidney Cancer	Procedure: Partial Nephrectomy (PN) Procedure: Radical Nephrectomy (RN) Procedure: Ablation therapy (AT) Diagnostic Test: Active Surveillance (AS)

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:

Anthropometric, pre-operative and comorbidity data (patient characteristics).
Imaging data e and pre-operative tumor features (tumor characteristics).
Intra-operative and post-operative data (treatment characteristics).
Histopathological analysis (tumor histopathological characteristics).
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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

10000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Jan 10, 2022

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2028

Arms and Interventions

Arm	Intervention/Treatment
Renal tumor patiens 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.	Procedure: Partial Nephrectomy (PN) Conservative removal of kidney tumor. The procedure can be performed either with an open or laparoscopic or robotic approach. Procedure: 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. Procedure: 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. Diagnostic Test: 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.

Arm

Intervention/Treatment

Renal tumor patiens

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.

Procedure: Partial Nephrectomy (PN)

Conservative removal of kidney tumor. The procedure can be performed either with an open or laparoscopic or robotic approach.

Procedure: 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.

Procedure: 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.

Diagnostic Test: 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.

Outcome Measures

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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: Anthropometric, pre-operative and comorbidity data (patient characteristics). Imaging data and pre-operative tumor features (tumor characteristics). Centre facilities (laparoscopic/robot assisted, interventional radiology) , volume centre (PN/RN ratio, availability of Multidisciplinary Tumor Board) Intra-operative and post-operative data (treatment characteristics). 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 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 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institute of Urology, University of Southern California.	Los Angeles	California	United States	90007
2	University of California San Diego, Moores Cancer Center	San Diego	California	United States	92037
3	Stanford University	Stanford	California	United States	94304
4	Loyola University Medical Center, Edward Hines VA Hospital	Chicago	Illinois	United States	60141
5	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
6	VCU Health System	Richmond	Virginia	United States	23298
7	Swedish Hospital	Seattle	Washington	United States	98122
8	Medical University of Vienna, Vienna General Hospital	Vienna		Austria	1090
9	University of Bruxelles	Bruxelles		Belgium	1050
10	University Hospitals Leuven	Leuven		Belgium	3000
11	Onze Lieve Vrouw Hospital	Leuven		Belgium	8500
12	Santa Casa da Misericórdia de Fortaleza	Fortaleza		Brazil	60025
13	University of Patras	Patras		Greece	265 04
14	Urology, Andrology & Kidney Transplantation Unit, University of Bari	Bari		Italy	70121
15	Policlinico S. Orsola Malpighi	Bologna		Italy	40138
16	Department of Urology, University of Florence, Unit of Oncologic Minimally-Invasive Urology and Andrology, Careggi Hospital	Firenze		Italy	50100
17	Policlinico Riuniti, Università di Foggia.	Foggia		Italy	71122
18	Division of Urology, University of Genoa,Policlinico San Martino Hospital	Genova		Italy	16132
19	Azienda Ospedaliera Policlinico "G. Martino", Università di Messina.	Messina		Italy	98124
20	San Raffaele Scientific Institute, Milan, Italy; Division of Experimental Oncology/Unit of Urology, URI, IRCCS San Raffaele Hospital	Milano		Italy	20132
21	Policlinico Istituto Europeo di Oncologia (IEO)	Milano		Italy	20141
22	Istituto Nazionale dei Tumori Fondazione Senatore "G. Pascale"	Napoli		Italy	80131
23	Institute Oncology Veneto (IOV)	Padova		Italy	35128
24	Humanitas Hospital	Rozzano		Italy	20089
25	Università degli Studi di Torino, Ospedale S. Luigi Gonzaga.	Torino		Italy	10043
26	Università degli studi di Torino, Ospedale Molinette	Torino		Italy	10126
27	AOUI Verona	Verona		Italy	37126
28	Jikei University School of Medicine	Tokyo		Japan	105-8461
29	Amsterdam University Medical Centers	Amsterdam		Netherlands	1118
30	European Health Center	Otwock		Poland	05-400
31	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie	Warsaw		Poland	00-001
32	N.N. Blokhin National Medical Research Center of Oncology	Moscow		Russian Federation	119571
33	NG Teng Fong General Hospital	Singapore		Singapore	6090606
34	Fundaciò Puigvert	Barcelona		Spain	08025
35	Hospital Universitario Ramón y Cajal, University of Alcalá	Madrid		Spain	28034
36	Bristol Urological Institute	Bristol		United Kingdom	BS10 5NB
37	Guy's Hospital	London		United Kingdom	SE1 9RT

Sponsors and Collaborators

Azienda Ospedaliero-Universitaria Careggi
Società Italiana di Urologia (SIU)
Italian Group for Advanced Laparo-Endoscopic and Robotic Urologic Surgery (AGILE)

Investigators

Principal Investigator: Andrea Minervini, Prof., Dipartimento di Medicina Clinica e Sperimentale Via o Piazza Largo Brambilla 3 - 50134 Firenze (Italy)