Hereditary Renal Cell Carcinoma: Is Age an Independent Criterion for Genetic Testing? A Large Cohort from a Latin America Referral Center

Main Article Content

Tomás Carminatti
Patricio Aitor García Marchiñena
Ignacio Pablo Tobia González
Valeria de Miguel
Marcelo Martín Serra
Pablo Germán Kalfayan
Alberto Manuel Jurado


Hereditary renal cell carcinoma, genetic testing, early-onset renal cell carcinoma, VHL, Age criteria in Hereditary renal cell carcinoma


Although age younger than 46 years has been an independent criterion for genetic testing in hereditary renal cell carcinoma (hRCC), there is a lack of evidence in the literature. This study aims to analyze whether a 46-year-old cut-off should be considered an independent genetic testing criterion and to elucidate risk factors predicting a positive genetic test. Observational study from January 2010 to December 2021. All patients under 46 years with a non-metastatic kidney mass and surgical indication were included. We assume patients who relapse in the first 5 years of follow-up could have a positive genetic test. As risk factors for relapse, ergo positive genetic test, we consider those patients who presented multifocal, bilateral, or previous renal tumor. Of 2,232 nephrectomies for kidney cancer, 301 patients met the inclusion criteria. The median follow-up was 60 months (IQR 29-101). The estimated five-year RFS was 94.4% (95% CI 91.3-97.5). Tumor size, previous renal tumor, multifocality, bilaterality, and pT3 or pT4 stage were independent recurrence risk factors. Genetic testing was performed on 24 patients. 10 patients had pathogenic variants in the test, 8 of which recurred during their life. 46-year-old cut-off has shown low performance in genetic testing. Therefore, we recommend that it be considered only if other hRCC risk criteria exist. Multifocality, bilaterality, and previous renal tumor could predict a positive genetic test.

Abstract 355 | PDF Downloads 785 HTML Downloads 29 XML Downloads 5


1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018 [Internet]. Vol. 68, CA: A Cancer Journal for Clinicians. 2018. pp. 7–30. 10.3322/caac.21442

2. Adeniran AJ, Shuch B, Humphrey PA. Hereditary Renal Cell Carcinoma Syndromes: Clinical, Pathologic, and Genetic Features. Am J Surg Pathol. 2015;39(12):e1–18. 10.1097/PAS.0000000000000562

3. Shuch B, Vourganti S, Ricketts CJ, Middleton L, Peterson J, Merino MJ, et al. Defining early-onset kidney cancer: implications for germline and somatic mutation testing and clinical management. J Clin Oncol. 2014;32(5):431–7. 10.1200/JCO.2013.50.8192

4. Lui ST, Shuch B. Genetic Testing in Kidney Cancer Patients: Who, When, and How? Eur Urol Focus. 2019;5(6):973–6. 10.1016/j.euf.2019.09.005

5. Maher ER. Hereditary renal cell carcinoma syndromes: diagnosis, surveillance, and management [Internet]. World J of Urol. 2018; 1891–8. 10.1007/s00345-018-2288-5

6. Nguyen KA, Syed JS, Espenschied CR, LaDuca H, Bhagat AM, Suarez-Sarmiento A, et al. Advances in the diagnosis of hereditary kidney cancer: Initial results of a multigene panel test [Internet]. Vol. 123, Cancer. 2017. pp. 4363–71. 10.1002/cncr.30893

7. Horton WA, Wong V, Eldridge R. Von Hippel-Lindau disease: clinical and pathological manifestations in nine families with 50 affected members. Arch Intern Med. 1976 Jul;136(7):769–77. 10.1001/archinte.136.7.769

8. Maher ER, Yates JR, Harries R, Benjamin C, Harris R, Moore AT, et al. Clinical features and natural history of von Hippel-Lindau disease. Q J Med. 1990;77(283):1151–63. 10.1093/qjmed/77.2.1151

9. Byler TK, Bratslavsky G. Hereditary renal cell carcinoma: genetics, clinical features, and surgical considerations. World J Urol. 2014;32(3):623–30. 10.1007/s00345-014-1287-4

10. Capitanio U, Rosiello G, Erdem S, Rowe I, Kara O, Roussel E, et al. Clinical, surgical, pathological and follow-up features of kidney cancer patients with Von Hippel-Lindau syndrome: novel insights from a large consortium. World J Urol. 2021;39(8):2969–75. 10.1007/s00345-020-03574-5

11. Reaume MN, Graham GE, Tomiak E, Kamel-Reid S, Jewett MAS, Bjarnason GA, et al. Canadian guideline on genetic screening for hereditary renal cell cancers. Can Urol Assoc J. 2013;7(9–10):319–23. 10.5489/cuaj.1496

12. Motzer RJ, Jonasch E, Boyle S, Carlo MI, Manley B, Agarwal N, et al. NCCN Guidelines Insights: Kidney Cancer, Version 1.2021. J Natl Compr Canc Netw. 2020;18(9):1160–70. 10.6004/jnccn.2020.0043

13. Bratslavsky G, Mendhiratta N, Daneshvar M, Brugarolas J, Ball MW, Metwalli A, et al. Genetic risk assessment for hereditary renal cell carcinoma: Clinical consensus statement. Cancer. 2021;127(21):3957–66. 10.1002/cncr.33679

14. Ponzone R, Giai M, Roagna R, Sgro L, Biglia N, Welch H, et al. Clinical and ethical issues in diagnosing hereditary breast cancer (review). Int J Oncol. 1997;10(2):323–8. 10.3892/ijo.10.2.323

15. Kessler S, Field T, Worth L, Mosbarger H. Attitudes of persons at risk for Huntington disease toward predictive testing. Am J Med Genet. 1987;26(2):259–70. 10.1002/ajmg.1320260204

16. Kokorovic A, Thomas A, Serrano-Lomelin J, Ferguson M, Rendon RA. Clinical predictors of a positive test result in patients undergoing genetic evaluation for a hereditary kidney cancer syndrome. Can Urol Assoc J. 2020;14(8):274–80. 10.5489/cuaj.6264

17. Kushnir I, Kirk L, Mallick R, Kim RH, Graham GE, Breau RH, et al. Application of Hereditary Renal Cell Carcinoma Risk Criteria to a Large Prospective Database. Clin Oncol. 2020;32(1):e10–5. 10.1016/j.clon.2019.07.010