1. Siegel R, Miller, K, Jemal A. Cancer Statistics, 2015. CA Cancer J Clin 2015;65:5–29.
2. Eble JN, Sauter G, Epstein JI, Sesterhenn IA. Pathology and genetics. Tumors of the urinary system and male genital organs. Lyon: IARC Press; 2004.
3. Chow WH, Gridley G, Fraumeni JF Jr, Jarvholm B. Obesity, hypertension, and the risk of kidney cancer in men. N Engl J Med 2000;343:1305–11.
4. Cohen H, McGovern F. Renal-cell carcinoma. N Engl J Med 2005;353:2477–90
5. Yao M, Yoshida M, Kishida T, et al. VHL tumor suppres sor gene alterations associated with good prognosis in sporadic clear-cell renal carcinoma. J Natl Cancer Inst 2002;94:1569–75.
6. Iliopoulos O, Kibel A, Gray S, Kaelin WG Jr. Tumour suppression by the human von Hippel-Lindau gene product. Nat Med 1995;1:822–6
7. Chen F, Kishida T, Duh FM, et al. Suppression of growth of renal carcinoma cells by the von Hippel-Lindau tumor suppressor gene. Cancer Res 1995;55:4804–7.
8. Iliopoulos O, Levy AP, Jiang C, et al. Negative regulation of hypoxia-inducible genes by the von Hippel Lindau protein. Proc Natl Acad Sci U S A 1996;93:10595–9.
9. Nickerson ML, Warren MB, Toro JR, et al. Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Bir- Hogg-Dube syndrome. Cancer Cell 2002;2:157–64
10. Shuch B, Vorganit S, Ricketts CJ, et al. Defining early-onset kidney cancer: implications for germline and somatic mutation testing and clinical management. J Clin Oncol 2014;32:431–7.
11. Bukowski RM. Immunotherapy in renal cell carcinoma. Oncology 1999;13:801–10.
12. Mueller-Lisse UG, Mueller-Lisse UL. Imaging of advanced renal cell carcinoma. World J Urol 2010;28:253–61.
13. Edge SB, Byrd DR, Compton CC, et al, eds. AJCC cancer staging manual, 7th ed. New York: Springer Science and Business Media LLC; 2010.
14. O’Malley RL, Godoy G, Kanofsky JA, Taneja SS. The necessity of adrenalectomy at the time of radical nephrectomy: a systematic review. J Urol 2009;181:2009–17.
15. McDougal S, Wein AJ, Kavoussi LR, et al. Campbell-Walsh Urology. 10th ed. Philadelphia (PA): Saunders; 2012.
16. Colombo JR Jr, Haber GP, Kelovsek JE, et al. Seven years after laparoscopic radical nephrectomy: oncologic and renal functional outcomes. Urology 2008:71:1149–54.
17. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Ca 2013;49:1374–403.
18. Weight CJ, Larson BT, Fergany AF, et al. Nephrectomy induced chronic renal insufficiency is associated with increased risk of cardiovascular death and death from any cause in patients with localized cT1b renal masses. J Urol 2010;183:1317–23.
19. Van Poppel H, Da Pozzo L, Albrecht W, et al. A prospective, randomized EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma. Eur Urol 2011;59:543–52.
20. Smaldone MC, Fung C, Uzzo RG, Hass NB. Adjuvant and neoadjuvant therapies in high-risk renal cell carcioma. Hematol Oncol Clin North Am 2011;25:765–91.
21. NCCN clinical practice guidelines in oncology. Version 3.2016. www.nccn.org. Accessed July 13, 2016
22. El Dib R, Touma NJ, Kapoor A. Cryoablation vs radiofrequency ablation for the treatment of renal cell carcinoma: a meta-amalysis of case series studies. BJU Int 2012;110:510–6.
23. Theodorescu D. Cancer cryotherapy: evolution and biology. Rev Urol 2004;6 Suppl 4:S9–S19.
24. Khiatani V, Dixon RG. Renal ablation update. Sem Intervent Radiol 2014;31:157–66.
25. Yu J, Liang P, Yu XL, et al. US-guided percutaneous microwave ablation of renal cell carcinoma: intermediate-term results. Radiol 2012;263:900–8.
26. Castle SM, Salas N, Leveillee RJ. Initial experience using microwave ablation therapy for renal tumor treatment: 18- month follow-up. Urology 2011;77:792–7.
27. Pech M, Janitzky A, Wendler JJ, et al. Irreversible electroporation of renal cell carcinoma: a first-in-man phase I clinical study. Cardiovasc Intervent Radiol 2011;34:132–8.
28. Chow WH, Devesa SS, Warren JL, Fraumeni JF Jr. Rising incidence of renal cell cancer in the United States. JAMA 1999;281:1628–31.
29. Jayson M, Sanders H. Increased incidence of serendipitously discovered renal cell carcinoma. Urology 1998;51:203–5.
30. Pierorazio PM, Johnson MH, Ball MW, et al. Five-year analysis of a multi-institutional prospective clinical trial of delayed intervention and surveillance for small renal masses: the DISSRM registry. Eur Urol 2015;68:408–15.
31. Jewett MA, Mattar K, Basiuk J, et al. Active surveillance of small renal masses: progression patterns of early stage kidney cancer. Eur Urol 2011;60:39–44.
32. Chawla SN, Crispen PL, Hanlon AL, et al. The natural history of observed enhancing renal masses: meta-analysis and review of the world literature. J Urol 2006;175:425–31.
33. Smaldone MC, Kutikov A, Egleston BL, et al. Small renal masses progressing to metastases under active surveillance: a systematic review and pooled analysis. Cancer 2012;118:997–1006.
34. Williamson TJ, Pearson JR, Ischia J, et al.Guideline of guidelines: follow-up after nephrectomy for renal cell carcinoma. BJU Int 2016;117:555–62.
35. Donat S, Diaz M, Bishoff JT, et al. Follow-up for clinically localized renal neoplasms: AUA Guideline. J Urol 2013;190:407–16.
36. Janzen NK, Kim HL, Figlin RA, Bell-degrun AS. Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin North Am 2003:30:843–52.
37. Gupta K, Miller JD, Li JZ, Russell MW, Charbonneau C. Epidemiologic and socio-economic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev 2008;34:193–205.
38. Mekhail T, Abou-Jawde R, Boumerhi G, et al. Validation and extension of the Memorial Sloan-Kettering Prognostic Factors Model for Survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol 2005;23: 832–41.
39. Motzer RJ, Bacik J, Murphy BA, et al. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 2002;20:289–96.
40. Motzer RJ, Mazumdar M, Bacik J, et al. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 1999;17:2530–40.
41. Heng DY, Xie W, Regan MM. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 2009;27:5794–9.
42. Leibovich BC, Han KR, Bui MH, et al. Scoring algorithm to predict survival after nephrectomy and immunotherapy in patients with metastatic renal cell carcinoma: A stratification tool for prospective clinical trials. Cancer 2003;98:2566–77.
43. Flanigan RC, Mickisch G, Sylvester R, et al. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol 2004;171:1071–6.
44. Choueiri TK, Xie W, Kollmannsberger C, et al. The impact of cytoreductive nephrectomy on survival of patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor targeted therapy. J Urol 2011;185:60–6.
45. Chapin BF, Delacroix SE Jr, Culp SH, et al. Safety of presurgical targeted therapy in the setting of metastatic renal cell carcinoma. Eur Urol 2011;60:964–71.
46. Hutson TE, Lesovoy V, Al-Shukri S, et al. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomized open-label phase 3 trial. Lancet Oncol 2013;14:1287–94.
47. Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metatastic renal cell carcinoma: a randomized, double-blind phase III trial. Lancet 2007;370:2103–11.
48. Escudier B, Bellmunt J, Negrier S, et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol 2010;28:2144–50.
49. McDermott DF, Cheng SC, Signoretti S, et al. The high-dose aldesleukin “select”trial: a trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma. Clin Cancer Res 2015;21:561–8.
50. Motzer RJ, Hutson TE, Cella D, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med 2013;369:722–31.
51. Escudier B, Eisen T, Stadler WM, et al. Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cell global evaluation trial. J Clin Oncol 2009;27:3312–8.
52. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356:115–24.
53. Motzer RJ, Hutson TE, Tomczak P, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 2009;27:3584–90.
54. Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007;356:2271–81.
55. Motzer RJ, Hutson TE, Glen H, et al. Lenvatinib, everolimus and the combination in patients with metastatic renal cell carcinoma: a randomized, phase 2, open label, multicenter trial. Lancet Oncology 2015;16:1473–82.
56. Lexi-Comp, Inc. (Lexi-Drugs® ). Lexi-Drugs version 2.3.3. Lexicomp. Wolters Kluwer Health, Inc. Hudson, OH.
57. Choueiri TK, Plantade A, Elson P, et al. Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. J Clin Oncol 2008;26:127–31.
58. Lee JL, Ahn JH, Lim HY, et al. Multicenter phase II study of sunitinib in patients with non-clear cell renal cell carcinoma. Ann Oncol 2012;23:2108–14.
59. Armstrong AJ, Broderick S, Eisen T, et al. Final clinical results of a randomized phase II international trial of everolimus vs. sunitinib in patients with metastatic non-clear cell renal cell carcinoma (ASPEN). ASCO Meeting Abstracts 2015;33:4507.
60. Chowdhury S, Matrana MR, Tsang C, et al. Systemic therapy for metastatic non-clear-cell renal cell carcinoma: recent progress and future directions. Hematol Oncol Clin North Am 2011;25:853–69.
61. Escudier B, Droz JP, Rolland F, et al. Doxorubicin and ifosfamide in patients with metastatic sarcomatoid renal cell carcinoma: a phase II study of the Genitourinary Group of the French Federation of Cancer Centers. J Urol 2002; 168–71
62. Nanus DM, Garino A, Milowsky MI, et al. Active chemotherapy for sarcomatoid and rapidly progressing renal cell carcinoma. Cancer 2004;101:1545–51.
63. Michaelson MD, McKay RR, Werner L, et al. Phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid and/or poor-risk metastatic renal cell carcinoma. Cancer 2015;121:3435–43.
64. McDermott DF, Cheng SC, Signoretti S, et al. The high-dose aldesleukin “select”trial: a trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma. Clin Cancer Res 2015;21:561–8
65. Cho DC, Puzanov I, Regan MM, et al. Retrospective analysis of the safety and efficacy of interleukin-2 after prior VEGF-targeted therapy in patients with advanced renal cell carcinoma. J Immunother 2009;32:181–5.
66. Pyrhönen S, Salminen E, Ruutu M, et al. Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. J Clin Oncol 1999;17:2859–67.
67. Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators. Lancet 1999;353:14–7.
68. Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 2003;349:427–34.
69. Atkinson BJ, Kalra S, Wang X, et al. Clinical outcomes for patients with metastatic renal cell carcinoma treated with alternative sunitinib schedules. J Urol 2014;191:611–8.
70. Kollmannsberger C, Bjarnason G, Burnett P, et al. Sunitinib in metastatic renal cell carcinoma: recommendations for management of noncardiovascular toxicities. Oncologist 2011;16:543–53.
71. Najjar YG, Mittal K, Elson P, et al. A 2 weeks on and 1 week off schedule of sunitinib is associated with decreased toxicity in metastatic renal cell carcinoma. Eur J Cancer 2014;50:1084–9.
72. Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 2010;28:1061–8.
73. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007;356:125–34
74. Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 2011;378:1931–9.
75. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015;373:1814–23.
76. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR) final results from a randomized, open-label, phase 3 trial. Lancet Oncology 2016;17:917–27.
77. Bjornsti MA, Houghton PJ. The TOR pathway: a target for cancer therapy. Nat Rev Cancer 2004;4:335–48.
78. Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372:449–56.
79. Brahmer J, Tykodi S, Chow L, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012;366:2455–65.
80. Thomson RH, Kuntz SM, Leibovich BC, et al. Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow up. Cancer Res 2006;66: 3381–5.
81. Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015;373:1803–13.