REFERENCES
1. Global Cancer Observatory: Cancer Today. Lyon, France: international agency for research on cancer. Available from: https://gco.iarc.fr/today [Last accessed on 3 Jun 2021].
2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.
3. Cancer research UK (2020) kidney cancer statistics. Available from: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/kidney-cancer [Last accessed on 3 Jun 2021].
4. Hsieh JJ, Purdue MP, Signoretti S, et al. Renal cell carcinoma. Nat Rev Dis Primers 2017;3:17009.
5. Haddad AQ, Marhulis V. Tumour and patient factors in renal cell carcinoma towards personalised therapy. Nat Rev Urol 2015;12:253-62.
6. Heng DYC, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicentre study. J Clin Oncol 2009;27:5794-9.
7. Motzer RJ, Bacik J, Murphy BA, et al. Interferon-alpha as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 2002;20:289-96.
8. Heng DYC, Xie W, Regan MM, et al. External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model :a population-based study. Lancet Oncol 2013;14:141-8.
9. Ko JJ, Xie W, Kroeger N, et al. The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study. Lancet Oncol 2015;16:293-300.
10. Wells JC, Stukalin I, Norton C, et al. Third-line targeted therapy in metastatic renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium. Eur Urol 2017;71:204-9.
11. Kroeger N, Xie W, Lee JL, et al. Metastatic non-clear cell renal cell carcinoma treated with targeted therapy agents: characterization of survival outcome and application of the International mRCC Database Consortium criteria. Cancer 2013;119:2999-3006.
12. Yip S, Wells C, Moreira RB, Wong A, Heng DYC. Real world experience of immuno-oncology agents in metastatic renal cell carcinoma: results from the IMDC. J Clin Oncol 2017;35:492.
13. Cella D, Grunwald V, Escudier B, et al. Patient-reported outcomes of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib (CheckMate 214): a randomised, phase 3 trial. Lancet Oncol 2019;20:297-310.
14. Srigley JR, Delahunt B, Eble JN, et al. ISUP renal tumor panel. The International Society of Urological Pathology (ISUP) vancouver classification of renal neoplasia. Am J Surg Pathol 2013;37:1469-89.
15. Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 2013;499:43-9.
16. Patard J-J, Rioux-Leclercq N, Fergelot P. Understanding the importance of smart drugs in renal cell carcinoma. Eur Urol 2006;49:633-43.
17. Sternberg CN, Calabro F, Bracarda S, et al. Safety and efficacy of sunitinib in patients from Italy with metastatic renal cell carcinoma: final results form an expanded-access trial. Oncology 2015;8:273-80.
18. Chowdhury B, Porter EG, Stewart JC, et al. PBRM1 regulates the expression of genes involved in metabolism and cell adhesion in renal clear cell carcinoma. PLoS One 2016;11:e0153718.
19. Hsieh JJ, Chen D, Wang PI, et al. Genomic biomarkers of a randomized trial comparing first-line everolimus and sunitinib in patients with metastatic renal cell carcinoma. Eur Urol 2017;71:405-14.
20. Carlo M, Manley B, Patil S, et al. Genomic alterations and outcomes with VEGF-targeted therapy in patients with clear cell renal cell carcinoma. Kidney Cancer 2017;1:49-56.
21. Creighton CJ. A gene transcription signature of the Akt/mTOR pathway in clinical breast tumors. Oncogene 2007;26:4648-55.
22. Cao G, Wu X, Wang Z, et al. What is the optimum systemic treatment for advanced/metastatic renal cell carcinoma of favourable, intermediate and poor risk, respectively? BMJ Open 2020;10:eo34626.
23. Loewth R, Jacinto E, Wullschleger S, et al. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 2002;10:457-68.
25. Kwiatkowski DJ, Choueiri TK, Fay AP, et al. Mutations in TSC1, TSC2, and MTOR are associated with response to rapalogs in patients with metastatic renal cell carcinoma. Clin Cancer Res 2016;22:2445-52.
26. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma. N Engl J Med 2018;378:1277-90.
27. Motzer RJ, Escudier B, McDermott DF, et al. CheckMate 025 Investigators. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015;373:1803-13.
28. Escudier B, Tannir NM, McDermott DF, et al. CheckMate 214: efficacy and safety of nivolumab + ipilimumab (N+I) v sunitinib (S) for treatment-naïve advanced or metastatic renal cell carcinoma (mRCC), including IMDC risk and PD-L1 expression subgroups. Ann Oncol 2017;28:V621-2.
29. Mazza C, Escudier B, Albiges L. Nivolumab in renal cell carcinoma: latest evidence and clinical potential. Ther Adv Med Oncol 2017;9:171-81.
30. Iacovelli, R, Nole F, Verri E, et al. Prognostic role of PD-L1 expression in renal cell carcinoma. A systematic review and meta-analysis. Target Oncol 2016;11:143-48.
31. RH, Dong H, Kwon ED. Implications of B7-H1 expression in clear cell carcinoma of the kidney for prognostication and therapy. Clin Cancer Res 2007;13:709s-15s.
32. Miao D, Margolis CA, Gao W, et al. Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science 2018;59:801-6.
33. Brannon AR, Reddy A, Seiler M, et al. Molecular stratification of clear cell renal cell carcinoma by consensus clustering reveals distinct subtypes and survival patterns. Genes Cancer 2010;1:152-63.
34. de Velasco G, Culhane AC, Fay AP, et al. Molecular subtypes improve prognostic value of International Metastatic Renal Cell Carcinoma Database Consortium prognostic model. Oncol 2017;22:286-92.
35. Durinck S, Stawiski EW, Pavia-Jimenez A, et al. Spectrum of diverse genomic alterations define non-clear cell renal carcinoma subtypes. Nat Genet 2015;47:13-21.
36. Linehan WM, Spellman PT, Ricketts CJ, et al. Cancer genome atlas research network. Comprehensive molecular characterization of papillary renal-cell carcinoma. N Engl J Med 2016;374:135-45.
37. Choueiri TK, Vaishampayan U, Rosenberg JE, et al. Phase II and biomarker study of the dual MET/VEGFR2 inhibitor foretinib in patients with papillary renal cell carcinoma. J Clin Oncol 2013;31:181-6.
38. Choueiri TK, Plimack E, Arkenau HT, et al. Biomarker-based phase II trial of savolitinib in patients with advanced papillary renal cell cancer. J Clin Oncol 2017;35:2993-3001.
39. Choueiri TK, Halabi S, Sanford BL, et al. Cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: the Alliance A031203 CABOSUN trial. J Clin Oncol 2017;35:591-7.
40. Choueiri TK, Escudier B, Powles T, et al. METEOR Investigators. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015;373:1814-23.
41. Gad S, Lefevre SH, Khoo SK, et al. Mutations in BHD and TP53 genes, but not in HNF1beta gene, in a large series of sporadic chromophobe renal cell carcinoma. Br J Cancer 2007;96:336-40.
42. Higgins JP, Shinghal R, Gill H, et al. Gene expression patterns in renal cell carcinoma assessed by complementary DNA microarray. Am J Pathol 2003;162:925-32.
43. Yamazaki K, Sakamoto M, Ohta T, et al. Overexpression of KIT in chromophobe renal cell carcinoma. Oncogene 2003;22:847-52.
44. Haitel A, Susani M, Wick N, et al. c-kit overexpression in chromophobe renal cell carcinoma is not associated with c-kit mutation of exons 9 and 11. Am J Surg Pathol 2005;29:842.
45. Polascik TJ, Cairns P, Epstein JI, et al. Distal nephron renal tumors: microsatellite allelotype. Cancer Res 1996;56:1892-15.
46. Choueiri TK, Motzer RJ. Systemic therapy for metastatic renal-cell carcinoma. N Engl J Med 2017;376:354-66.
47. Gerlinger M, Rowan AJ, Horswell S, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012;366:883-92.
48. Pal SK, Sonpavde G, Agarwal N, et al. Evolution of circulating tumor DNA profile from first-line to subsequent therapy in metastatic renal cell carcinoma. Eur Urol 2017;72:557-64.
49. Park I, Lee JL, Ahn JH, et al. Active surveillance for metastatic or recurrent renal cell carcinoma. J Cancer Res Clin Oncol 2014;140:1421-8.
50. Rini BI, Dorff TB, Elson P, et al. Active surveillance in metastatic renal-cell carcinoma: a prospective, phase 2 trial. Lancet Oncol 2016;17:1317-24.
51. Heng DYC, Wells JC, Rini BI, et al. Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium. Eur Urol 2014;66:704-10.
52. Bex A, Mulders P, Jewett MAS, et al. Immediate versus deferred cytoreductive nephrectomy (CN) in patients with synchronous metastatic renal cell carcinoma (mRCC) receiving sunitinib (EORTC 30073 SURTIME). Ann Oncol 2017;28:V622.
53. Méjean A, Ravaud A, Thezenas S, et al. Sunitinib alone or after Nephrectomy in metastatic renal-cell carcinoma. N Engl J Med 2018;379:417-27.
54. Méjean A, Thezenas S, Chevreau C, et al. Cytoreductive nephrectomy (CN) in metastatic renal cancer (mRCC): Update on Carmena trial with focus on intermediate IMDC-risk population. J Clin Oncol 2019;37:4508-8.
55. 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.
56. Pal SK, Nelson RA, Vogelzang N. Disease-specific survival in de novo metastatic renal cell carcinoma in the cytokine and targeted therapy era. PLoS One 2013;8:e63341.
57. Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumanb plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomized, double-blind phase III trial. Lancet 2007;370(9605):2103-11.
59. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Eng J Med 2010:363711-23.
60. Antonia SJ, López-Martin JA, Bendell J, et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol 2016;17:883-95.
61. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2019;380:1103-15.
62. Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2019;380:1103-15.
63. Choueiri TK, Powles T, Burotto M, et al. CheckMate 9ER Investigators. Nivolumab plus Cabozantinib versus Sunitinib for advanced renal-cell carcinoma. N Engl J Med 2021;384:829-41.
64. Motzer RJ, Escudier B, Gannon A, et al. Sunitinib: ten years of successful clinical use and study in advanced renal cell carcinoma. Oncologist 2017;22:41-52.
65. Gee MS, Procopio WN, Makonnen S, et al. Tumor vessel development and maturation impose limits on the effectiveness of anti-vascular therapy. Am J Pathol 2003;162:183-93.
66. Kotecha RR, Motzer RJ, Voss MH. Towards individualized therapy for metastatic renal cell carcinoma. Nature 2019;16:621-33.
67. Gao W, Li W, Xiao T, Liu XS, Kaelin WG Jr. Inactivation of the PBRM1 tumor suppressor gene amplifies the HIF-response in VHL-/- clear cell renal carcinoma. Proc Natl Acad Sci U S A 2017;114:1027-32.
68. Motzer R, Alekseev B, Rha SY, et al. CLEAR Trial Investigators. Lenvatinib plus Pembrolizumab or Everolimus for advanced renal cell carcinoma. N Engl J Med 2021;384:1289-300.
69. Grunwald V, Powles T, Choueiri TK, et al. Lenvatinib plus everolimus or pembrolizumab versus sunitinib in advanced renal cell carcinoma: study design and rationale. Future Oncol 2019;15:929-41.
70. Rini BI, Powles T, Atkins MB, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet 2019;393:2404-15.
71. Al-Marrawi MY, Rini BI, Harshman LC, et al. International mRCC Database Consortium. The association of clinical outcome to first-line VEGF-targeted therapy with clinical outcome to second-line VEGF-targeted therapy in metastatic renal cell carcinoma patients. Target Oncol 2013;8:203-9.
72. Rini BI, Pal SK, Escudier BJ, et al. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study. Lancet 2020;21:95-104.
73. Zakharia Y, Singer EA, Ross R, Joshi M, Alva AS. Phase Ib/II study of durvalumab and guadecitabine in advanced kidney cancer Big Ten Cancer Research Consortium BTCRC GU16-043. JCO 2021;39:328.
74. Choueiri TK, Bauer TM, Mcdermott DF, et al. Phase 2 study of the oral hypoxia-inducible factor 2α (HIF-2α) inhibitor MK-6482 in combination with cabozantinib in patients with advanced clear cell renal cell carcinoma (ccRCC). J Clin Oncol 2021;39:272.
75. Kollmannsberger C. Sunitinib side effects as surrogate biomarkers of efficacy. Can Urol Assoc J 2016;10:S245-7.
76. Rini BI, Cohen DP, Lu DR, et al. Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst 2011;103:763-73.
77. Wasserstrum Y, Kornowski R, Raanani P, Leader A, Pasvolsky O, Iakobishvili Z. Hypertension in cancer patients treated with anti-angiogenic based regimens. Cardiooncology 2015:7;1-6.
78. Bianchi M, Sun M, Jeldres C, et al. Distribution of metastatic sites in renal cell carcinoma: a population-based analysis. Ann Oncol 2012;23:973-80.
79. Kavolius JP, Mastorakos DP, Pavlovich C, et al. Resection of metastatic renal cell carcinoma. J Clin Oncol 1998;16:2261-6.
80. Wang CJ, Christie A, Lin MH, et al. Safety and efficacy of stereotactic ablative radiation therapy for renal cell carcinoma extracranial metastases. Int J Radiat Oncol Biol Phys 2017;98:91-100.
81. Aoun HD, Littrup PJ, Jaber M, et al. Percutaneous cryoablation of renal tumors: is it time for a new paradigm shift? J Vasc Interv Radiol 2017;28:1363-70.
82. Mehta S, Illidge T, Choudhury A. Immunotherapy with radiotherapy in urological malignancies. Curr Opin Urol 2016;26:514-22.
83. EurekAlert! AAAS. No benefit from Pazopanib in advanced kidney cancer after surgery to remove metastases. Available from: https://www.eurekalert.org/pub_releases/2019-06/ecrg-nbf053119.php [Last accessed on 3 Jun 2021].
