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Screening Programs for Renal Cell Carcinoma: A Systematic Review by the EAU Young Academic Urologists Renal Cancer Working Group - Beyond the Abstract

The incidence of renal cell carcinoma (RCC) is increasing, with over 430.000 new cases diagnosed per year and over 175.000 new deaths per year in 2020 worldwide.1 Although most RCCs are diagnosed at an early stage in asymptomatic patients2 and up to 25% present with metastasis showing a 1-year and 5-year survival of 39% and 12%.3 The increasing prevalence of RCC4 coupled with a high proportion of asymptomatic patients, and a high mortality rate make RCC suitable for screening programs with the objective to increase early staged tumors and overall survival and decrease mortality and health care costs.5 However, several uncertainties still need to be addressed, including the magnitude of the benefit and harm, the overall cost, the optimal screening modality, and the target population.6 The present systematic review focused on providing an overview of RCC screening programs focusing on the clinical impact, potential benefits, and harms.

This systematic review was conducted according to the European Association of Urology guidelines and the PRISMA statement recommendations (PROSPERO ID: CRD42021283136) using the MEDLINE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases. Comparative and non-comparative studies including adult healthy subjects or at higher risk of developing RCC based on established risk factors with no prior history of RCC and no prior history of diseases increasing the risk of RCC undergoing any screening program were included.

Nine studies and one clinical trials were included. Eight studies reported results from RCC screening programs involving a total of 159 136 patients and four studies reported screening cost-analysis. The prevalence of RCC ranged between 0.02 and 0.22% and it was associated with the socio-demographic characteristics of the subjects; selection of the target population decreased, overall, the screening cost per diagnosis.  Cost­effectiveness modeling is also highly sensitive to the prevalence of RCC: targeted screening of higher-risk individuals, selected from the general population by means of established risk-stratification tools is likely to be the most cost­effective strategy. Only one clinical trial on RCC screening is currently ongoing (NCT05005195). This is a non-randomized open label feasibility study for a RCC screening program in patients enrolled in the Yorkshire Lung Screening Trial that offers subjects at high risk for lung cancer aged 55-80 a CT scan as part of a lung health check. The main outcomes are the program acceptability of both patients and healthcare workers, time to perform and review images, and provide an estimate of the prevalence of RCC at non-contrast CT screening in 55-80y smokers and ex-smokers.

Despite an increasing interest from patients and clinicians during the last decades, today, there is a relative lack of studies reporting the efficacy and cost-effectiveness of well-structured screening programs for RCC. There is no high-quality evidence to show that screening asymptomatic individuals by any biomarker- or imaging-based test would reduce RCC morbidity and/or mortality. Moreover, the optimal modality for RCC screening is still controversial. Targeting high-risk individuals and/or combining detection of RCC with other health checks such as lung cancer screening represent pragmatic options to improve the cost-effectiveness and reduce the potential harms of RCC screening. While waiting for the results of prospective clinical trials, further research is needed to develop and validate accurate risk prediction models for RCC, define the most cost-effective screening population, explore the acceptability of a screening program in the population, and assess whether RCC screening might lead to a survival benefit without further increasing overdiagnosis and overtreatment of localized renal masses.

Written by: Pietro Diana1,2* Tobias Klatte3 Daniele Amparore4,5 Riccardo Bertolo5,6 Umberto Carbonara5,7 Selcuk Erdem5,8 Alexandre Ingels5,9,10 Onder Kara5,11 Laura Marandino5,12 Michele Marchioni5,13,14 Stijn Muselaers5,15 Nicola Pavan5,16 Angela Pecoraro4,5 Alessio Pecoraro17 Eduard Roussel5,18 and Riccardo Campi5,17,19*

on behalf of the European Association of Urology (EAU) Young Academic Urologists (YAU) Renal Cancer group.

  1. Department of Urology, Fundació Puigvert, Autonoma University of Barcelona, Spain.
  2. Department of Urology, Humanitas Clinical and Research Institute IRCCS, Rozzano, Italy.
  3. Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany
  4. Division of Urology, Department of Oncology, School of Medicine, San Luigi Hospital, University of Turin, Orbassano, Turin, Italy.
  5. European Association of Urology (EAU) Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, The Netherlands.
  6. Department of Urology, San Carlo Di Nancy Hospital, Rome, Italy.
  7. Department of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari, Italy.
  8. Division of Urologic Oncology, Department of Urology, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey.
  9. Department of Urology, University Hospital Henri Mondor, APHP, 51 Avenue du Maréchal de Lattre de Tassigny, 94010, Créteil, France.
  10. Biomaps, UMR1281, INSERM, CNRS, CEA, Université Paris Saclay, Villejuif, France.
  11. Department of Urology, Kocaeli University School of Medicine, Kocaeli, Turkey.
  12. Department of Medical Oncology, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy.
  13. Department of Medical, Oral and Biotechnological Sciences, Laboratory of Biostatistics, University "G. D'Annunzio" Chieti-Pescara, Chieti, Italy.
  14. Department of Urology, SS Annunziata Hospital, "G. D'Annunzio" University of Chieti, Chieti, Italy.
  15. Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
  16. Urology Clinic, Department of Medical, Surgical and Health Science, University of Trieste, Trieste, Italy.
  17. Unit of Urological Robotic Surgery and Renal Transplantation, Careggi Hospital, University of Florence, Florence, Italy.
  18. Department of Urology, University Hospitals Leuven, Leuven, Belgium.
  19. European Association of Urology (EAU) Young Academic Urologists (YAU) Renal Cancer Working Group, Arnhem, The Netherlands.
  20. Unit of Urological Robotic Surgery and Renal Transplantation, Careggi Hospital, University of Florence, Florence, Italy.
  21. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

References:

  1. International Agency for Research on Cancer (World Health Organization). Kidney: Globocan 2020 The Global Cancer Observatory. Globocan 2020. 2020;419:1-2. https://gco.iarc.fr/today/data/factsheets/cancers/29-Kidney-fact-sheet.pdf.
  2. Selby PJ, Banks RE, Gregory W, et al. Methods for the evaluation of biomarkers in patients with kidney and liver diseases: multicentre research programme including ELUCIDATE RCT. Program Grants Appl Res. 2018;6(3):1-528. doi:10.3310/pgfar06030
  3. Office for National Statistics. Office for National Statistics, Cancer survival by stage at diagnosis for England (2013-2017). 2019.
  4. Foreman KJ, Marquez N, Dolgert A, et al. Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016–40 for 195 countries and territories. Lancet. 2018;392(10159):2052-2090. doi:10.1016/S0140-6736(18)31694-5
  5. Reitblat C, Bain PA, Porter ME, et al. Value-Based Healthcare in Urology: A Collaborative Review. Eur Urol. 2021;79(5):571-585. doi:10.1016/j.eururo.2020.12.008
  6. Usher-Smith J, Simmons RK, Rossi SH, Stewart GD. Current evidence on screening for renal cancer. Nat Rev Urol. 2020;17(11):637-642. doi:10.1038/s41585-020-0363-3

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