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Current evidence on screening for renal cancer

Nature Reviews Urology volume 17, pages 637–642 (2020)Cite this article

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Abstract

Renal cell carcinoma (RCC) incidence is increasing worldwide. A high proportion of individuals are asymptomatic at diagnosis, but RCC has a high mortality rate. These facts suggest that RCC meets some of the criteria for screening, and a new analysis shows that screening for RCC could potentially be cost-effective. Targeted screening of high-risk individuals is likely to be the most cost-effective strategy to maximize the benefits and reduce the harms of screening. However, the size of the benefit of earlier initiation of treatment and the overall cost-effectiveness of screening remains uncertain. The optimal screening modality and target population is also unclear, and uncertainties exist regarding the specification and implementation of a screening programme. Before moving to a fully powered trial of screening, future work should focus on the following: developing and validating accurate risk prediction models; developing non-invasive methods of early RCC detection; establishing the feasibility, public acceptability and potential uptake of screening; establishing the prevalence of RCC and stage distribution of RCC detected by screening; and evaluating the potential harms of screening, including the impact on quality of life, overdiagnosis and over-treatment.

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References

  1. Jones, J. et al. The kidney cancer research priority-setting partnership: identifying the top 10 research priorities as defined by patients, caregivers, and expert clinicians. Can. Urol. Assoc. J. 11, 379–387 (2017).

    Google Scholar 

  2. Motzer, R. J. Perspective: what next for treatment? Nature 537, S111 (2016).

    CAS  Google Scholar 

  3. Rossi, S. H. et al. Essential research priorities in renal cancer: a modified Delphi consensus statement. Eur. Urol. Focus 6, 991–998 (2019).

    Google Scholar 

  4. Rossi, S. H. et al. Setting research priorities in partnership with patients to provide patient-centred urological cancer care. Eur. Urol. 75, 891–893 (2019).

    Google Scholar 

  5. Znaor, A., Lortet-Tieulent, J., Laversanne, M., Jemal, A. & Bray, F. International variations and trends in renal cell carcinoma incidence and mortality. Eur. Urol. 67, 519–530 (2015).

    Google Scholar 

  6. Rossi, S. H., Klatte, T., Usher-Smith, J. & Stewart, G. D. Epidemiology and screening for renal cancer. World J. Urol. 36, 1341–1353 (2018).

    Google Scholar 

  7. Hock, L. M., Lynch, J. & Balaji, K. C. Increasing incidence of all stages of kidney cancer in the last 2 decades in the United States: an analysis of surveillance, epidemiology and end results program data. J. Urol. 167, 57–60 (2002).

    Google Scholar 

  8. Lightfoot, N. et al. Impact of noninvasive imaging on increased incidental detection of renal cell carcinoma. Eur. Urol. 37, 521–527 (2000).

    CAS  Google Scholar 

  9. Selby, P. J. et al. Methods for the evaluation of biomarkers in patients with kidney and liver diseases: multicentre research programme including ELUCIDATE RCT (NIHR Journals Library, 2018).

  10. Cancer Research UK. Kidney Cancer Statistics http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/kidney-cancer (2020).

  11. Office for National Statistics. Cancer Survival by Stage at Diagnosis for England https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/cancersurvivalbystageatdiagnosisforenglandexperimentalstatistics/adultsdiagnosed20122013and2014andfollowedupto2015 (2016).

  12. Spouge, A. R., Wilson, S. R. & Wooley, B. Abdominal sonography in asymptomatic executives: prevalence of pathologic findings, potential benefits, and problems. J Ultrasound Med. 15, 763–767 (1996).

    CAS  Google Scholar 

  13. Fujii, Y., Ajima, J., Oka, K., Tosaka, A. & Takehara, Y. Benign renal tumors detected among healthy adults by abdominal ultrasonography. Eur. Urol 27, 124–127 (1995).

    CAS  Google Scholar 

  14. Mihara, S., Kuroda, K., Yoshioka, R. & Koyama, W. Early detection of renal cell carcinoma by ultrasonographic screening — based on the results of 13 years screening in Japan. Ultrasound Med. Biol. 25, 1033–1039 (1999).

    CAS  Google Scholar 

  15. National Screening Committee. Criteria for Appraising the Viability, Effectiveness and Appropriateness of a Screening Programme https://www.gov.uk/government/publications/evidence-review-criteria-national-screening-programmes/criteria-for-appraising-the-viability-effectiveness-and-appropriateness-of-a-screening-programme (2015).

  16. Wilson, J. M. G., Jungner, G. Principles and practice of screening for disease. Public Health Paper Number 34. (WHO, 1968).

  17. Fenton, J. J. & Weiss, N. S. Screening computed tomography: will it result in overdiagnosis of renal carcinoma? Cancer 100, 986–990 (2004).

    Google Scholar 

  18. Rossi, S. H. et al. Meta-analysis of the prevalence of renal cancer detected by abdominal ultrasonography. Br. J. Surg. 104, 648–659 (2017).

    CAS  Google Scholar 

  19. Saad, A. M. et al. Trends in renal-cell carcinoma incidence and mortality in the United States in the last 2 decades: a SEER-based study. Clin. Genitourin. Cancer 17, 46–57 (2019).

    Google Scholar 

  20. Turner, R. M. 2nd, Morgan, T. M. & Jacobs, B. L. Epidemiology of the small renal mass and the treatment disconnect phenomenon. Urol. Clin. North Am. 44, 147–154 (2017).

    Google Scholar 

  21. Hollingsworth, J. M., Miller, D. C., Daignault, S. & Hollenbeck, B. K. Rising incidence of small renal masses: a need to reassess treatment effect. J. Natl Cancer Inst. 98, 1331–1334 (2006).

    Google Scholar 

  22. Smaldone, M. C. et al. Understanding treatment disconnect and mortality trends in renal cell carcinoma using tumor registry data. Med Care 55, 398–404 (2017).

    Google Scholar 

  23. Welch, H. G., Skinner, J. S., Schroeck, F. R., Zhou, W. & Black, W. C. Regional variation of computed tomographic imaging in the United States and the risk of nephrectomy. JAMA Intern. Med. 178, 221–227 (2018).

    Google Scholar 

  24. Bangma, C. H. et al. Outcomes of a bladder cancer screening program using home hematuria testing and molecular markers. Eur. Urol. 64, 41–47 (2013).

    Google Scholar 

  25. Messing, E. M. et al. Long-term outcome of hematuria home screening for bladder cancer in men. Cancer 107, 2173–2179 (2006).

    Google Scholar 

  26. Messing, E. M. et al. Comparison of bladder cancer outcome in men undergoing hematuria home screening versus those with standard clinical presentations. Urology 45, 387–396 (1995).

    CAS  Google Scholar 

  27. Ljungberg, B. et al. European Association of Urology guidelines on renal cell carcinoma: the 2019 update. Eur. Urol. 75, 799–810 (2019).

    Google Scholar 

  28. Beinfeld, M. T., Wittenberg, E. & Gazelle, G. S. Cost-effectiveness of whole-body CT screening. Radiology 234, 415–422 (2005).

    Google Scholar 

  29. Ishikawa, S. et al. Mass screening of multiple abdominal solid organs using mobile helical computed tomography scanner — a preliminary report. Asian J. Surg. 30, 118–121 (2007).

    Google Scholar 

  30. Wernli, K. J., Rutter, C. M., Dachman, A. H. & Zafar, H. M. Suspected extracolonic neoplasms detected on CT colonography: literature review and possible outcomes. Acad. Radiol. 20, 667–674 (2013).

    Google Scholar 

  31. US Preventive Services Task Force et al. Screening for colorectal cancer: US preventive services task force recommendation statement. JAMA 315, 2564–2575 (2016).

    Google Scholar 

  32. ISRCTN Registry. The Yorkshire Lung Screening Trial http://www.isrctn.com/ISRCTN42704678 (2020).

  33. Bobridge, A., Price, K., Gill, T. K. & Taylor, A. W. Influencing cancer screening participation rates-providing a combined cancer screening program (a ‘One Stop’ Shop) could be a potential answer. Front. Oncol. 7, 308 (2017).

    Google Scholar 

  34. Labeit, A. & Peinemann, F. Breast and cervical cancer screening in Great Britain: dynamic interrelated processes. Health Econ. Rev. 5, 32 (2015).

    Google Scholar 

  35. Riccabona, M. et al. Renal masses — evaluation by amplitude coded colour Doppler sonography and multiphasic contrast-enhanced CT. Acta Radiol. 40, 457–461 (1999).

    CAS  Google Scholar 

  36. Darwood, R. et al. Twenty-year review of abdominal aortic aneurysm screening in men in the county of Gloucestershire, United Kingdom. J. Vasc. Surg. 56, 8–13 (2012).

    Google Scholar 

  37. Wanhainen, A. et al. Outcome of the Swedish nationwide abdominal aortic aneurysm screening program. Circulation 134, 1141–1148 (2016).

    Google Scholar 

  38. Mizuma, Y., Watanabe, Y., Ozasa, K., Hayashi, K. & Kawai, K. Validity of sonographic screening for the detection of abdominal cancers. J. Clin. Ultrasound 30, 408–415 (2002).

    Google Scholar 

  39. Filipas, D. et al. Screening for renal cell carcinoma using ultrasonography: a feasibility study. BJU Int. 91, 595–599 (2003).

    CAS  Google Scholar 

  40. Uppot, R. N. Technical challenges of imaging & image-guided interventions in obese patients. Br. J. Radiol. 91, 20170931 (2018).

    Google Scholar 

  41. Kyrgiou, M. et al. Adiposity and cancer at major anatomical sites: umbrella review of the literature. BrMedJ 356, j477 (2017).

    Google Scholar 

  42. Warshauer, D. M. et al. Detection of renal masses: sensitivities and specificities of excretory urography/linear tomography, US, and CT. Radiology 169, 363–365 (1988).

    CAS  Google Scholar 

  43. Tosaka, A. et al. Incidence and properties of renal masses and asymptomatic renal cell carcinoma detected by abdominal ultrasonography. J. Urol. 144, 1097–1099 (1990).

    CAS  Google Scholar 

  44. Ficarra, V. et al. Incidental detection beyond pathological factors as prognostic predictor of renal cell carcinoma. Eur. Urol. 43, 663–669 (2003).

    Google Scholar 

  45. Patard, J. J., Rodriguez, A., Rioux-Leclercq, N., Guille, F. & Lobel, B. Prognostic significance of the mode of detection in renal tumours. BJU Int. 90, 358–363 (2002).

    Google Scholar 

  46. Stephenson, A. J., Kuritzky, L. & Campbell, S. C. Screening for urologic malignancies in primary care: pros, cons, and recommendations. Cleve. Clin. J. Med. 74 (Suppl. 3), S6–S14 (2007).

    Google Scholar 

  47. Golombos, D. M. et al. Minimally invasive vs open nephrectomy in the modern era: does approach matter? World J. Urol. 35, 1557–1568 (2017).

    Google Scholar 

  48. Rossi, S. H. et al. A decision analysis evaluating screening for kidney cancer using focused renal ultrasound. Eur. Urol. Focus https://doi.org/10.1016/j.euf.2019.09.002 (2019).

  49. Lotan, Y. et al. Renal-cell carcinoma risk estimates based on participants in the prostate, lung, colorectal, and ovarian cancer screening trial and national lung screening trial. Urol. Oncol. 34, 167 e9–e116 (2016).

    Google Scholar 

  50. Malaeb, B. S. et al. The utility of screening renal ultrasonography: identifying renal cell carcinoma in an elderly asymptomatic population. BJU Int. 95, 977–981 (2005).

    Google Scholar 

  51. Shea, M. W. A proposal for a targeted screening program for renal cancer. Front. Oncol. 3, 207 (2013).

    Google Scholar 

  52. Usher-Smith, J. A., Sharp, S. J., Luben, R. & Griffin, S. J. Development and validation of lifestyle-based models to predict incidence of the most common potentially preventable cancers. Cancer Epidemiol. Biomarkers Prev. 28, 67–75 (2019).

    Google Scholar 

  53. Wu, Y. et al. Genetic scores based on risk-associated single nucleotide polymorphisms (SNPs) can reveal inherited risk of renal cell carcinoma. Oncotarget 7, 18631–18637 (2016).

    Google Scholar 

  54. Scelo, G. et al. KIM-1 as a blood-based marker for early detection of kidney cancer: a prospective nested case-control study. Clin. Cancer Res. 24, 5594–5601 (2018).

    CAS  Google Scholar 

  55. Frantzi, M. et al. Discovery and validation of urinary biomarkers for detection of renal cell carcinoma. J. Proteom. 98, 44–58 (2014).

    CAS  Google Scholar 

  56. Starke, N., Singla, N., Haddad, A. & Lotan, Y. Long-term outcomes in a high-risk bladder cancer screening cohort. BJU Int. 117, 611–617 (2016).

    Google Scholar 

  57. Mitchell, T. J. et al. Timing the landmark events in the evolution of clear cell renal cell cancer: TRACERx renal. Cell 173, 611–623 (2018).

    CAS  Google Scholar 

  58. Gerstung, M. et al. The evolutionary history of 2,658 cancers. Nature 578, 122–128 (2020).

    CAS  Google Scholar 

  59. Meisel, S. F. et al. Adjusting the frequency of mammography screening on the basis of genetic risk: attitudes among women in the UK. Breast 24, 237–241 (2015).

    Google Scholar 

  60. Meisel, S. F. et al. Population-based, risk-stratified genetic testing for ovarian cancer risk: a focus group study. Public Health Genomics 16, 184–191 (2013).

    CAS  Google Scholar 

  61. Grebe, S. K. & Erickson, L. A. Screening for kidney cancer: is there a role for aquaporin-1 and adipophilin? Mayo Clin. Proc. 85, 410–412 (2010).

    Google Scholar 

  62. Volpe, A. et al. The natural history of incidentally detected small renal masses. Cancer 100, 738–745 (2004).

    Google Scholar 

  63. Jewett, M. A. et al. Active surveillance of small renal masses: progression patterns of early stage kidney cancer. Eur. Urol. 60, 39–44 (2011).

    Google Scholar 

  64. Volpe, A. European Active SurveillancE of Renal Cell Carcinoma Study Facts and Figures https://uroweb.org/wp-content/uploads/EASE-Facts-figures-05-03-2020.pdf (2016).

  65. Corcoran, A. T. et al. A review of contemporary data on surgically resected renal masses — benign or malignant? Urology 81, 707–713 (2013).

    Google Scholar 

  66. Borghesi, M. et al. Active surveillance for clinically localized renal tumors: an updated review of current indications and clinical outcomes. Int. J. Urol. 22, 432–438 (2015).

    Google Scholar 

  67. Frank, I. et al. Solid renal tumors: an analysis of pathological features related to tumor size. J. Urol. 170, 2217–2220 (2003).

    Google Scholar 

  68. Neves, J. B. et al. Protocol for a feasibility study of a cohort embedded randomised controlled trial comparing nephron sparing treatment (NEST) for small renal masses. BMJ Open. 9, e030965 (2019).

    Google Scholar 

  69. Blick, C., Ritchie, A. W. S., Eisen, T. & Stewart, G. D. Improving outcomes in high-risk, nonmetastatic renal cancer: new data and ongoing trials. Nat. Rev. Urol. 14, 753–759 (2017).

    Google Scholar 

  70. Kidney Cancer UK. Patient Survey Results Autumn 2018 https://www.kcuk.org.uk/patient-survey-autumn-2018/ (2018).

  71. Klatte, T., Lam, J. S., Shuch, B., Belldegrun, A. S. & Pantuck, A. J. Surveillance for renal cell carcinoma: why and how? When and how often? Urol. Oncol. 26, 550–554 (2008).

    Google Scholar 

  72. Usher-Smith, J. A. et al. External validation of risk prediction models for incident colorectal cancer using UK Biobank. Br. J. Cancer 118, 750–759 (2018).

    CAS  Google Scholar 

  73. Lee, A. et al. BOADICEA: a comprehensive breast cancer risk prediction model incorporating genetic and nongenetic risk factors. Genet. Med. 21, 1708–1718 (2019).

    Google Scholar 

  74. Li, K. et al. Selecting high-risk individuals for lung cancer screening: a prospective evaluation of existing risk models and eligibility criteria in the German EPIC cohort. Cancer Prev. Res. 8, 777–785 (2015).

    CAS  Google Scholar 

  75. Usher-Smith, J. A., Emery, J., Kassianos, A. P. & Walter, F. M. Risk prediction models for melanoma: a systematic review. Cancer Epidemiol. Biomarkers Prev. 23, 1450–1463 (2014).

    Google Scholar 

  76. Usher-Smith, J. A., Walter, F. M., Emery, J. D., Win, A. K. & Griffin, S. J. Risk prediction models for colorectal cancer: a systematic review. Cancer Prev. Res. 9, 13–26 (2016).

    CAS  Google Scholar 

  77. Rabjerg, M., Mikkelsen, M. N., Walter, S. & Marcussen, N. Incidental renal neoplasms: is there a need for routine screening? A Danish single-center epidemiological study. APMIS 122, 708–714 (2014).

    Google Scholar 

  78. Luciani, L. G., Cestari, R. & Tallarigo, C. Incidental renal cell carcinoma-age and stage characterization and clinical implications: study of 1092 patients (1982–1997). Urology 56, 58–62 (2000).

    CAS  Google Scholar 

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Acknowledgements

The work of J.U.S., G.D.S. and S.H.R. on screening in RCC is funded by a research grant from Kidney Cancer UK. J.U.S. is supported by a Cancer Research UK Cancer Prevention Fellowship (C55650/A21464). G.D.S. is supported by Cancer Research UK Cambridge Cancer Centre (Major Centre Award A25117). S.H.R. is supported by The Urology Foundation, the Renal Cancer Research Fund and a Cancer Research UK Clinical Research Fellowship. We thank patient representatives Philip Dondi and Phil Alsop for their helpful comments on this paper.

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Authors and Affiliations

  1. The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

    Juliet Usher-Smith

  2. Department of Public Health, Bartolins Allé 2, University of Aarhus, Aarhus C, Denmark

    Rebecca K. Simmons

  3. Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge Biomedical Campus, Cambridge, UK

    Sabrina H. Rossi & Grant D. Stewart

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R.K.S. wrote the manuscript and all authors provided a substantial contribution to the discussion of content and reviewed and/or edited the article before submission.

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Correspondence to Grant D. Stewart.

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Competing interests

G.D.S. has received educational grants from Pfizer, AstraZeneca and Intuitive Surgical; consultancy fees from Pfizer, Merck, EUSA Pharma and CMR Surgical; travel expenses from Pfizer and speaker fees from Pfizer. R.K.S. is the Chair of the International Advisory Board for the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation. The other authors declare no competing interests.

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Nature Reviews Urology thanks C. Szczylik and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Glossary

Allocation bias

Overestimation of mortality rates in registry data owing to increasing numbers of individuals diagnosed with disease and therefore ‘eligible’ to die with the disease over time.

Lead-time bias

Overestimation of survival duration owing to screening detecting disease earlier (during the asymptomatic phase), meaning individuals with screen-detected cancer appear to live longer simply owing to earlier diagnosis (rather than a true improvement in survival).

Length-time bias

Overestimation of survival owing to screening detecting more slowly progressive and less aggressive disease in asymptomatic individuals whereas individuals with more aggressive disease are more likely to be diagnosed outside a screening programme owing to symptoms.

Treatment disconnect

The paradoxical rise in overall and cancer-specific mortality despite increased detection and treatment of renal cell carcinoma.

Value of information analysis

In health economic evaluations, decisions regarding whether to adopt an intervention are taken in the context of uncertainty; the value of information analysis assesses the value of additional evidence to reduce decision uncertainty, suggesting whether further research into this topic might be a good use of resources.

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Usher-Smith, J., Simmons, R.K., Rossi, S.H. et al. Current evidence on screening for renal cancer. Nat Rev Urol 17, 637–642 (2020). https://doi.org/10.1038/s41585-020-0363-3

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