Advanced renal cell carcinoma, clear-cell renal cell carcinoma (ccRCC), Metastatic Renal Cell Carcinoma, renal cell carcinoma (RCC), second-line therapy, immunotherapy, Immune Checkpoint Inhibitors, Angiogenesis, Tyrosine Kinase Inhibitors, VEGF inhibitors

1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022 Jan;72(1):7–33. http://dx.doi.org/10.3322/caac.21708
2. SEER Stat fact sheets: Kidney and renal pelvis [Internet]. [cited 2022 Jun 5]. Available from: http://seer.cancer.gov/statfacts/html/kdrp.html
3. Kane CJ, Mallin K, Ritchey J, Cooperberg MR, Carroll PR. Renal cell cancer stage migration: Analysis of the national cancer data base. Cancer. 2008 Jul 1;113(1):78–83. http://dx.doi.org/10.1002/cncr.23518
4. Tannir NM, Pal SK, Atkins MB. Second-line treatment landscape for renal cell carcinoma: A comprehensive review. Oncologist. 2018 May;23(5):540–55. http://dx.doi.org/10.1634/theoncologist.2017-0534
5. Shamash J, Steele JP, Wilson P, Nystrom M, Ansell W, Oliver RT. IPM chemotherapy in cytokine refractory renal cell cancer. Br J Cancer. 2003 May 19;88(10):1516–21. http://dx.doi.org/10.1038/sj.bjc.6600934
6. Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019 Mar 21;380(12):1116–27. http://dx.doi.org/10.1056/NEJMoa1816714
7. Choueiri TK, Powles T, Burotto M, Escudier B, Bourlon MT, Zurawski B, et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021 Mar 4;384(9):829–41. http://dx.doi.org/10.1056/NEJMoa2026982
8. Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021 Apr 8;384(14):1289–300. http://dx.doi.org/10.1056/NEJMoa2035716
9. Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277–90. http://dx.doi.org/10.1056/NEJMoa1712126
10. Grimm MO, Leucht K, Foller S. Risk stratification and treatment algorithm of metastatic renal cell carcinoma. J Clin Med. 2021 Nov 16;10(22):5339. http://dx.doi.org/10.3390/jcm10225339
11. Powles T, Albiges L, Bex A, Grünwald V, Porta C, Procopio G, et al. ESMO clinical practice guideline update on the use of immunotherapy in early stage and advanced renal cell carcinoma. Ann Oncol. 2021 Dec;32(12):1511–19. http://dx.doi.org/10.1016/j.annonc.2021.09.014
12. Rizzo M, Porta C. Sunitinib in the treatment of renal cell carcinoma: An update on recent evidence. Ther Adv Urol. 2017 Jun 29;9(8):195–207. http://dx.doi.org/10.1177/1756287217713902
13. Knox JJ, Barrios CH, Kim TM, Cosgriff T, Srimuninnimit V, Pittman K, et al. Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC. Ann Oncol. 2017 Jun 1;28(6):1339–45. http://dx.doi.org/10.1093/annonc/mdx075
14. Oudard S, Geoffrois L, Guillot A, Chevreau C, Deville JL, Falkowski S, et al. Clinical activity of sunitinib rechallenge in metastatic renal cell carcinoma-results of the REchallenge with SUnitinib in MEtastatic RCC (RESUME) study. Eur J Cancer. 2016 Jul;62:28–35. http://dx.doi.org/10.1016/j.ejca.2016.04.003
15. Grande E, Alonso-Gordoa T, Reig O, Esteban E, Castellano D, Garcia-Del-Muro X, et al. Results from the INMUNOSUN-SOGUG trial: A prospective phase II study of sunitinib as a second-line therapy in patients with metastatic renal cell carcinoma after immune checkpoint-based combination therapy. ESMO Open. 2022 Apr;7(2):100463. http://dx.doi.org/10.1016/j.esmoop.2022.100463
16. Wells JC, Dudani S, Gan CL, Stukalin I, Azad AA, Liow E, et al. Clinical effectiveness of second-line sunitinib following immuno-oncology therapy in patients with metastatic renal cell carcinoma: A real-world study. Clin Genitourin Cancer. 2021 Aug;19(4):354–61. http://dx.doi.org/10.1016/j.clgc.2021.03.006
17. Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: Results of a randomized phase III trial. J Clin Oncol. 2010 Feb 20;28(6):1061–8. http://dx.doi.org/10.1200/JCO.2009.23.9764
18. Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013 Aug 22;369(8):722–31. http://dx.doi.org/10.1056/NEJMoa1303989
19. Escudier B, Porta C, Bono P, Powles T, Eisen T, Sternberg CN, et al. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol. 2014 May 10;32(14):1412–18. http://dx.doi.org/10.1200/JCO.2013.50.8267
20. Hainsworth JD, Rubin MS, Arrowsmith ER, Khatcheressian J, Crane EJ, Franco LA. Pazopanib as second-line treatment after sunitinib or bevacizumab in patients with advanced renal cell carcinoma: A Sarah Cannon Oncology Research Consortium Phase II trial. Clin Genitourin Cancer. 2013 Sep;11(3):270–5. http://dx.doi.org/10.1016/j.clgc.2013.04.006
21. Bellmunt J, Esteban E, Del Muro XG, Sepúlveda JM, Maroto P, Gallardo E, et al. Pazopanib as second-line antiangiogenic treatment in metastatic renal cell carcinoma after tyrosine kinase inhibitor (TKI) failure: A phase 2 trial exploring immune-related biomarkers for testing in the post-immunotherapy/TKI era. Eur Urol Oncol. 2021 Jun;4(3):502–5. http://dx.doi.org/10.1016/j.euo.2019.07.014
22. Kok VC, Kuo JT. Pazopanib as a second-line treatment for non-cytokine-treated metastatic renal cell carcinoma: A meta-analysis of the effect of treatment. BMC Urol. 2016 Jul 4;16(1):34. http://dx.doi.org/10.1186/s12894-016-0156-4
23. Cao X, Tang D, Ratto B, Poole A, Ravichandran S, Jin L, et al. Real-world clinical outcomes of pazopanib immediately after discontinuation of immunotherapy for advanced renal cell carcinoma. Clin Genitourin Cancer. 2020 Feb;18(1):e37–45. http://dx.doi.org/10.1016/j.clgc.2019.10.010
24. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Staehler M, et al. Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol. 2009 Jul 10;27(20):3312–18. http://dx.doi.org/10.1200/JCO.2008.19.5511
25. Amzal B, Fu S, Meng J, Lister J, Karcher H. Cabozantinib versus everolimus, nivolumab, axitinib, sorafenib and best supportive care: A network meta-analysis of progression-free survival and overall survival in second line treatment of advanced renal cell carcinoma. PLoS One. 2017 Sep 8;12(9):e0184423. http://dx.doi.org/10.1371/journal.pone.0184423
26. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): A randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931–9. http://dx.doi.org/10.1016/S0140-6736(11)61613-9
27. Motzer RJ, Escudier B, Tomczak P, Hutson TE, Michaelson MD, Negrier S, et al. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: Overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):552–62. http://dx.doi.org/10.1016/S1470-2045(13)70093-7
28. Cella D, Escudier B, Rini B, Chen C, Bhattacharyya H, Tarazi J, et al. Patient-reported outcomes for axitinib vs sorafenib in metastatic renal cell carcinoma: Phase III (AXIS) trial. Br J Cancer. 2013 Apr 30;108(8):1571–8. http://dx.doi.org/10.1038/bjc.2013.145
29. Escudier B, Michaelson MD, Motzer RJ, Hutson TE, Clark JI, Lim HY, et al. Axitinib versus sorafenib in advanced renal cell carcinoma: Subanalyses by prior therapy from a randomised phase III trial. Br J Cancer. 2014 Jun 10;110(12):2821–8. http://dx.doi.org/10.1038/bjc.2014.244
30. Bracarda S, Bamias A, Casper J, Negrier S, Sella A, Staehler M, et al. Is axitinib still a valid option for mRCC in the second-line setting? Prognostic factor analyses from the AXIS trial. Clin Genitourin Cancer. 2019 Jun;17(3):e689–703. http://dx.doi.org/10.1016/j.clgc.2019.03.017
31. Tsimafeyeu I, Borisov P, Abdelgafur A, Leonenkov R, Novikova O, Guseva I, et al. Phase 2 multicenter single-arm study of second-line axitinib in favorable risk patients with metastatic renal cell carcinoma: FavorAx. Target Oncol. 2019 Feb;14(1):33–8. http://dx.doi.org/10.1007/s11523-018-0613-y
32. Ornstein MC, Pal SK, Wood LS, Tomer JM, Hobbs BP, Jia XS, et al. Individualised axitinib regimen for patients with metastatic renal cell carcinoma after treatment with checkpoint inhibitors: A multicentre, single-arm, phase 2 study. Lancet Oncol. 2019 Oct;20(10):1386–94. http://dx.doi.org/10.1016/S1470-2045(19)30513-3
33. Miyake H, Harada KI, Ozono S, Fujisawa M. Assessment of efficacy, safety, and quality of life of 124 patients treated with axitinib as second-line therapy for metastatic renal-cell carcinoma: Experience in real-world clinical practice in Japan. Clin Genitourin Cancer. 2017 Feb;15(1):122–8. http://dx.doi.org/10.1016/j.clgc.2016.06.019
34. Santoni M, Iacovelli R, Colonna V, Klinz S, Mauri G, Nuti M. Antitumor effects of the multi-target tyrosine kinase inhibitor cabozantinib: A comprehensive review of the preclinical evidence. Expert Rev Anticancer Ther. 2021 Sep;21(9):1029–54. http://dx.doi.org/10.1080/14737140.2021.1919090
35. Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): Final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):917–27. http://dx.doi.org/10.1016/S1470-2045(16)30107-3
36. Albiges L, Schmidinger M, Taguieva-Pioger N, Perol D, Grünwald V, Guemas E. CaboPoint: A phase II study of cabozantinib as second-line treatment in patients with metastatic renal cell carcinoma. Future Oncol. 2022 Mar;18(8):915–26. http://dx.doi.org/10.2217/fon-2021-1006
37. Rini BI, Pal SK, Escudier BJ, Atkins MB, Hutson TE, Porta C, et al. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): A phase 3, multicentre, randomised, controlled, open-label study. Lancet Oncol. 2020 Jan;21(1):95–104. http://dx.doi.org/10.1016/S1470-2045(19)30735-1
38. Pal SK, Escudier BJ, Atkins MB, Hutson TE, Porta C, Verzoni E, et al. Final overall survival results from a phase 3 study to compare tivozanib to sorafenib as third- or fourth-line therapy in subjects with metastatic renal cell carcinoma. Eur Urol. 2020 Dec;78(6):783–5. http://dx.doi.org/10.1016/j.eururo.2020.08.007
39. Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: A randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015 Nov;16(15):1473–82. http://dx.doi.org/10.1016/S1470-2045(15)00290-9
40. Pal SK, Puente J, Heng DYC, Glen H, Koralewski P, Stroyakovskiy D, et al. Assessing the safety and efficacy of two starting doses of lenvatinib plus everolimus in patients with renal cell carcinoma: A randomized phase 2 trial. Eur Urol. 2022;82(3):283–92. http://dx.doi.org/10.1016/j.eururo.2021.12.024
41. Vogelzang NJ, Monnette AM, Wang Y, Wan Y, Xie Y, Robert NJ, et al. Real-world clinical effectiveness of lenvatinib/everolimus in a heavily pretreated advanced/metastatic renal cell carcinoma population in the US Community oncology setting. Clin Genitourin Cancer. 2021 Dec;19(6):531–9. http://dx.doi.org/10.1016/j.clgc.2021.05.002
42. Motzer RJ, Escudier B, George S, Hammers HJ, Srinivas S, Tykodi SS, et al. Nivolumab versus everolimus in patients with advanced renal cell carcinoma: Updated results with long-term follow-up of the randomized, open-label, phase 3 CheckMate 025 trial. Cancer. 2020 Sep 15;126(18):4156–67. http://dx.doi.org/10.1002/cncr.33033
43. Xu JX, Maher VE, Zhang L, Tang S, Sridhara R, Ibrahim A, et al. FDA approval summary: Nivolumab in advanced renal cell carcinoma after anti-angiogenic therapy and exploratory predictive biomarker analysis. Oncologist. 2017 Mar;22(3):311–17. http://dx.doi.org/10.1634/theoncologist.2016-0476
44. Escudier B, Motzer RJ, Sharma P, Wagstaff J, Plimack ER, Hammers HJ, et al. Treatment beyond progression in patients with advanced renal cell carcinoma treated with nivolumab in CheckMate 025. Eur Urol. 2017 Sep;72(3):368–76. http://dx.doi.org/10.1016/j.eururo.2017.03.037
45. Gul A, Stewart TF, Mantia CM, Shah NJ, Gatof ES, Long Y, et al. Salvage ipilimumab and nivolumab in patients with metastatic renal cell carcinoma after prior immune checkpoint inhibitors. J Clin Oncol. 2020 Sep 20;38(27):3088–94. http://dx.doi.org/10.1200/JCO.19.03315
46. Vauchier C, Auclin E, Barthélémy P, Carril-Ajuria L, Ryckewaert T, Borchiellini D, et al. REchallenge of NIVOlumab (RENIVO) or nivolumab-ipilimumab in metastatic renal cell carcinoma: An ambispective multicenter study. J Oncol. 2022 Feb 18;2022:3449660. http://dx.doi.org/10.1155/2022/3449660
47. Lee CH, Shah AY, Rasco D, Rao A, Taylor MH, Di Simone C, et al. Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (study 111/KEYNOTE-146): A phase 1b/2 study. Lancet Oncol. 2021 Jul;22(7):946–58. http://dx.doi.org/10.1016/S1470-2045(21)00241-2
48. Powles T, Atkins MB, Escudier B, Motzer RJ, Rini BI, Fong L, et al. Efficacy and safety of atezolizumab plus bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with metastatic renal cell carcinoma in IMmotion150: A randomized phase 2 clinical trial. Eur Urol. 2021 May;79(5):665–73. http://dx.doi.org/10.1016/j.eururo.2021.01.003
49. Choueiri TK, Halabi S, Sanford BL, Hahn O, Michaelson MD, Walsh MK, 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 Feb 20;35(6):591–7. http://dx.doi.org/10.1200/JCO.2016.70.7398
50. Eichelberg C, Vervenne WL, De Santis M, Fischer von Weikersthal L, Goebell PJ, Lerchenmüller C, et al. SWITCH: A randomised, sequential, open-label study to evaluate the efficacy and safety of sorafenib-sunitinib versus sunitinib-sorafenib in the treatment of metastatic renal cell cancer. Eur Urol. 2015 Nov;68(5):837–47. http://dx.doi.org/10.1016/j.eururo.2015.04.017
51. Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, et al. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Sep 1;32(25):2765–72. http://dx.doi.org/10.1200/JCO.2013.54.6911
52. Suzuki K, Terakawa T, Furukawa J, Harada K, Hinata N, Nakano Y, et al. Clinical outcomes of second-line treatment following prior targeted therapy in patients with metastatic renal cell carcinoma: A comparison of axitinib and nivolumab. Int J Clin Oncol. 2020 Sep;25(9):1678–86. http://dx.doi.org/10.1007/s10147-020-01708-8
53. Suzuki K, Hara T, Terakawa T, Harada K, Fujisawa M. Efficacy of axitinib rechallenge in metastatic renal cell carcinoma. Int J Urol. 2021 Jun;28(6):702–3. http://dx.doi.org/10.1111/iju.14529
54. Motzer RJ, Jonasch E, Agarwal N, Alva A, Baine M, Beckermann K, et al. Kidney cancer, version 3.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2022 Jan;20(1):71–90. http://dx.doi.org/10.6004/jnccn.2022.0001
55. Santoni M, Aurilio G, Massari F, Grande E, Matrana MR, Rizzo M, et al. Nivolumab VERSUS cabozantinib as second-line therapy in patients with advanced renal cell carcinoma: A real-world comparison. Clin Genitourin Cancer. 2022 Jun;20(3):285–95. http://dx.doi.org/10.1016/j.clgc.2022.02.003
56. Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: Safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010 Jul 1;28(19):3167–75. http://dx.doi.org/10.1200/JCO.2009.26.7609
57. Cogdill AP, Andrews MC, Wargo JA. Hallmarks of response to immune checkpoint blockade. Br J Cancer. 2017 Jun 27;117(1):1–7. http://dx.doi.org/10.1038/bjc.2017.136
58. Waterhouse DM, Garon EB, Chandler J, McCleod M, Hussein M, Jotte R, et al. Continuous versus 1-year fixed-duration nivolumab in previously treated advanced non-small-cell lung cancer: CheckMate 153. J Clin Oncol. 2020 Nov 20;38(33):3863–73. http://dx.doi.org/10.1200/JCO.20.00131
59. Jenkins RW, Barbie DA, Flaherty KT. Mechanisms of resistance to immune checkpoint inhibitors. Br J Cancer. 2018;118(1):9–16. http://dx.doi.org/10.1038/bjc.2017.434
60. Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell. 2017;168 (4): 707–23. http://dx.doi.org/10.1016/j.cell.2017.01.017
61. Vlachostergios PJ. Resistance to pembrolizumab and axitinib in renal cell carcinoma: Clinical and genomic evaluation. J Kidney Cancer VHL. 2020 Jun 2;7(1):7–11. http://dx.doi.org/10.15586/jkcvhl.2020.135
62. Gobbini E, Charles J, Toffart AC, Leccia MT, Moro-Sibilot D, Giaj Levra M. Current opinions in immune checkpoint inhibitors rechallenge in solid cancers. Crit Rev Oncol Hematol. 2019 Dec;144:102816. http://dx.doi.org/10.1016/j.critrevonc.2019.102816
63. Anagnostou V, Smith KN, Forde PM, Niknafs N, Bhattacharya R, White J, et al. Evolution of neoantigen landscape during immune checkpoint blockade in non-small cell lung cancer. Cancer Discov. 2017 Mar;7(3):264–76. http://dx.doi.org/10.1158/2159-8290.CD-16-0828
64. Deeks ED. Belzutifan: First approval. Drugs. 2021 Nov;81(16):1921–7. http://dx.doi.org/10.1007/s40265-021-01606-x
65. Bauer TM, Choueiri TK, Papadopoulos KP, Plimack ER, Merchan JR, McDermott DF, et al. The oral HIF-2 α inhibitor MK-6482 in patients with advanced clear cell renal cell carcinoma (RCC): Updated follow-up of a phase I/II study. J Clin Oncol. 2021;39(Suppl 6):273. http://dx.doi.org/10.1200/JCO.2021.39.6_suppl.273
66. Choueiri TK, Bauer TM, Papadopoulos KP, Plimack ER, Merchan JR, McDermott DF, et al. Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: A phase 1 trial and biomarker analysis. Nat Med. 2021 May;27(5):802–5. http://dx.doi.org/10.1038/s41591-021-01324-7
67. Benamran D, Albiges L, Bex A, Giannarini G, Capitanio U, Rouprêt M, EAU Section of Oncological Urology (ESOU) Board. Treatment options for De Novo metastatic clear-cell renal cell carcinoma: Current recommendations and future insights. Eur Urol Oncol. 2022 Feb;5(1):125–33. http://dx.doi.org/10.1016/j.euo.2021.08.003
68. Donini M, Buti S, Massari F, Mollica V, Rizzo A, Montironi R, et al. Management of oligometastatic and oligoprogressive renal cell carcinoma: State of the art and future directions. Expert Rev Anticancer Ther. 2020 Jun;20(6):491–501. http://dx.doi.org/10.1080/14737140.2020.1770601
69. Santini D, Ratta R, Pantano F, De Lisi D, Maruzzo M, Galli L, et al. Outcome of oligoprogressing metastatic renal cell carcinoma patients treated with locoregional therapy: A multicenter retrospective analysis. Oncotarget. 2017 Aug 7;8(59):100708–16. http://dx.doi.org/10.18632/oncotarget.20022
70. Nagaraja H, Srivatsa N, Hemalatha S, Shweta S, Raghunath SK. Role of RPLND and metastasectomy in the management of oligometastatic renal cell carcinoma. Indian J Surg Oncol. 2018 Mar;9(1):105–9. http://dx.doi.org/10.1007/s13193-018-0722-1
71. Meyer CP, Sun M, Karam JA, Leow JJ, de Velasco G, Pal SK, et al. Complications after metastasectomy for renal cell carcinoma—A population-based assessment. Eur Urol. 2017 Aug;72(2):171–4. http://dx.doi.org/10.1016/j.eururo.2017.03.005
72. Sundet A, McConnell J, Walker K, Lindeque B. Intraoperative cryotherapy in the treatment of metastatic renal cell carcinoma of the bone. Orthopedics. 2021 Sep–Oct;44(5):e645–52. http://dx.doi.org/10.3928/01477447-20210817-04
73. Bang HJ, Littrup PJ, Goodrich DJ, Currier BP, Aoun HD, Heilbrun LK, et al. Percutaneous cryoablation of metastatic renal cell carcinoma for local tumor control: Feasibility, outcomes, and estimated cost-effectiveness for palliation. J Vasc Interv Radiol. 2012 Jun;23(6):770–7. http://dx.doi.org/10.1016/j.jvir.2012.03.002
74. Maciolek KA, Abel EJ, Best SL, Emamekhoo H, Averill SL, Ziemlewicz TJ, et al. Percutaneous microwave ablation for local control of metastatic renal cell carcinoma. Abdom Radiol (NY). 2018 Sep;43(9):2446–54. http://dx.doi.org/10.1007/s00261-018-1498-z
75. Ali M, Mooi J, Lawrentschuk N, McKay RR, Hannan R, Lo SS, et al. The role of stereotactic ablative body radiotherapy in renal cell carcinoma. Eur Urol. 2022 Jul 14:S0302-2838(22)02468-X. http://dx.doi.org/10.1016/j.eururo.2022.06.017
76. Masini C, Iotti C, De Giorgi U, Bellia RS, Buti S, Salaroli F, et al. Nivolumab in combination with stereotactic body radiotherapy in pretreated patients with metastatic renal cell carcinoma. Results of the phase II NIVES study. Eur Urol. 2022 Mar;81(3):274–82. http://dx.doi.org/10.1016/j.eururo.2021.09.016
77. Pryor D, Bressel M, Lawrentschuk N, Tran B, Mooi J, Lewin J, et al. A phase I/II study of stereotactic radiotherapy and pembrolizumab for oligometastatic renal tumours (RAPPORT): Clinical trial protocol. Contemp Clin Trials Commun. 2021 Jan 6;21:100703. http://dx.doi.org/10.1016/j.conctc.2021.100703
78. Kroeze SGC, Fritz C, Schaule J, Siva S, Kahl KH, Sundahl N, et al. Stereotactic radiotherapy combined with immunotherapy or targeted therapy for metastatic renal cell carcinoma. BJU Int. 2021 Jun;127(6):703–11. http://dx.doi.org/10.1111/bju.15284
79. All S, Garant A, Hannan R. Stereotactic ablative radiation (SAbR) for oligometastatic RCC. Semin Radiat Oncol. 2021 Jul;31(3):227–34. http://dx.doi.org/10.1016/j.semradonc.2021.02.002
80. Buti S, Bersanelli M, Viansone A, Leonetti A, Masini C, Ratta R, et al. Treatment outcome of metastatic lesions from renal cell carcinoma under going extra-cranial stereotactic body radioTHERapy: The together retrospective study. Cancer Treat Res Commun. 2020;22:100161. http://dx.doi.org/10.1016/j.ctarc.2019.100161
81. Liu Y, Long W, Zhang Z, Zhang Z, Mai L, Huang S, et al. Metastasis-directed stereotactic body radiotherapy for oligometastatic renal cell carcinoma: Extent of tumor burden eradicated by radiotherapy. World J Urol. 2021 Nov;39(11):4183–90. http://dx.doi.org/10.1007/s00345-021-03742-1
82. Franzese C, Marvaso G, Francolini G, Borghetti P, Trodella LE, Sepulcri M, et al. The role of stereotactic body radiation therapy and its integration with systemic therapies in metastatic kidney cancer: A multicenter study on behalf of the AIRO (Italian Association of Radiotherapy and Clinical Oncology) genitourinary study group. Clin Exp Metastasis. 2021 Dec;38(6):527–37. http://dx.doi.org/10.1007/s10585-021-10131-w
83. Zhang Y, Schoenhals J, Christie A, Mohamad O, Wang C, Bowman I, et al. Stereotactic ablative radiation therapy (SAbR) used to defer systemic therapy in oligometastatic renal cell cancer. Int J Radiat Oncol Biol Phys. 2019 Oct 1;105(2):367–75. http://dx.doi.org/10.1016/j.ijrobp.2019.07.023
84. Schoenhals JE, Mohamad O, Christie A, Zhang Y, Li D, Singla N, et al. Stereotactic ablative radiation therapy for oligoprogressive renal cell carcinoma. Adv Radiat Oncol. 2021 May 26;6(5):100692. http://dx.doi.org/10.1016/j.adro.2021.100692
85. Meyer E, Pasquier D, Bernadou G, Calais G, Maroun P, Bossi A, et al. Stereotactic radiation therapy in the strategy of treatment of metastatic renal cell carcinoma: A study of the Getug group. Eur J Cancer. 2018 Jul;98:38–47. http://dx.doi.org/10.1016/j.ejca.2018.04.008
86. De B, Venkatesan AM, Msaouel P, Ghia AJ, Li J, Yeboa DN, et al. Definitive radiotherapy for extracranial oligoprogressive metastatic renal cell carcinoma as a strategy to defer systemic therapy escalation. BJU Int. 2022 May;129(5):610–20. http://dx.doi.org/10.1111/bju.15541
87. Tang C, Msaouel P, Hara K, Choi H, Le V, Shah AY, et al. Definitive radiotherapy in lieu of systemic therapy for oligometastatic renal cell carcinoma: A single-arm, single-centre, feasibility, phase 2 trial. Lancet Oncol. 2021 Dec;22(12):1732–9. http://dx.doi.org/10.1016/S1470-2045(21)00528-3
88. Hannan R, Christensen M, Hammers H, Christie A, Paulman B, Lin D, et al. Phase II trial of stereotactic ablative radiation for oligoprogressive metastatic kidney cancer. Eur Urol Oncol. 2022 Apr;5(2):216–24. http://dx.doi.org/10.1016/j.euo.2021.12.001
89. Cheung P, Patel S, North SA, Sahgal A, Chu W, Soliman H, et al. Stereotactic radiotherapy for oligoprogression in metastatic renal cell cancer patients receiving tyrosine kinase inhibitor therapy: A phase 2 prospective multicenter study. Eur Urol. 2021 Dec;80(6):693–700. http://dx.doi.org/10.1016/j.eururo.2021.07.026
90. Barata PC, Mendiratta P, Kotecha R, Gopalakrishnan D, Juloori A, Chao ST, et al. Effect of switching systemic treatment after stereotactic radiosurgery for oligoprogressive, metastatic renal cell carcinoma. Clin Genitourin Cancer. 2018 Oct;16(5):413–19.e1. http://dx.doi.org/10.1016/j.clgc.2018.07.018
91. Staehler M, Goebell PJ, Müller L, Emde TO, Wetzel N, Kruggel L, et al. Rare patients in routine care: Treatment and outcome in advanced papillary renal cell carcinoma in the prospective German clinical RCC-Registry. Int J Cancer. 2020 Mar 1;146(5):1307–15. http://dx.doi.org/10.1002/ijc.32671
92. Hutson TE, Michaelson MD, Kuzel TM, Agarwal N, Molina AM, Hsieh JJ, et al. A single-arm, multicenter, phase 2 study of lenvatinib plus everolimus in patients with advanced non-clear cell renal cell carcinoma. Eur Urol. 2021 Aug;80(2):162–70. http://dx.doi.org/10.1016/j.eururo.2021.03.015
93. Lee CH, Voss MH, Carlo MI, Chen YB, Zucker M, Knezevic A, et al. Phase II trial of cabozantinib plus nivolumab in patients with non-clear-cell renal cell carcinoma and genomic correlates. J Clin Oncol. 2022 Jul 20;40(21):2333–41. http://dx.doi.org/10.1200/JCO.21.01944
94. Vogelzang NJ, Olsen MR, McFarlane JJ, Arrowsmith E, Bauer TM, Jain RK, et al. Safety and efficacy of nivolumab in patients with advanced non-clear cell renal cell carcinoma: Results from the phase IIIb/IV CheckMate 374 study. Clin Genitourin Cancer. 2020 Dec;18(6):461–8.e3. http://dx.doi.org/10.1016/j.clgc.2020.05.006
95. Graham J, Wells JC, Dudani S, Gan CL, Donskov F, Lee JL, et al. Outcomes of patients with advanced non-clear cell renal cell carcinoma treated with first-line immune checkpoint inhibitor therapy. Eur J Cancer. 2022 Aug;171:124–32. http://dx.doi.org/10.1016/j.ejca.2022.05.002
96. Tykodi SS, Gordan LN, Alter RS, Arrowsmith E, Harrison MR, Percent I, et al. Safety and efficacy of nivolumab plus ipilimumab in patients with advanced non-clear cell renal cell carcinoma: Results from the phase 3b/4 CheckMate 920 trial. J Immunother Cancer. 2022 Feb;10(2):e003844. http://dx.doi.org/10.1136/jitc-2021-003844
97. McDermott DF, Lee JL, Ziobro M, Suarez C, Langiewicz P, Matveev VB, et al. Open-label, single-arm, phase II study of pembrolizumab monotherapy as first-line therapy in patients with advanced non-clear cell renal cell carcinoma. J Clin Oncol. 2021 Mar 20;39(9):1029–39. http://dx.doi.org/10.1200/JCO.20.02365
98. Luzzago S, Palumbo C, Rosiello G, Knipper S, Pecoraro A, Mistretta FA, et al. Association between systemic therapy and/or cytoreductive nephrectomy and survival in contemporary metastatic non-clear cell renal cell carcinoma patients. Eur Urol Focus. 2021 May;7(3):598–607. http://dx.doi.org/10.1016/j.euf.2020.04.009
99. Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan VK, Maughan BL, et al. Belzutifan for renal cell carcinoma in von Hippel-Lindau disease. N Engl J Med. 2021 Nov 25;385(22):2036–46. http://dx.doi.org/10.1056/NEJMoa2103425
100. Choueiri TK, Bauer TM, McDermott DF, Arrowsmith R, Roy A, Perini RF, 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(Suppl 6):272. http://dx.doi.org/10.1200/JCO.2021.39.6_suppl.272
101. Tucker MD, Rini BI. Predicting response to immunotherapy in metastatic renal cell carcinoma. Cancers (Basel). 2020 Sep 18;12(9):2662. http://dx.doi.org/10.3390/cancers12092662
102. Motzer RJ, Choueiri TK, McDermott DF, Powles T, Vano YA, Gupta S, et al. Biomarker analysis from CheckMate 214: Nivolumab plus ipilimumab versus sunitinib in renal cell carcinoma. J Immunother Cancer. 2022 Mar;10(3):e004316. http://dx.doi.org/10.1136/jitc-2021-004316
103. Bi K, He MX, Bakouny Z, Kanodia A, Napolitano S, Wu J, et al. Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma. Cancer Cell. 2021 May 10;39(5):649–61.e5. http://dx.doi.org/10.1016/j.ccell.2021.02.015
104. Banchereau R, Leng N, Zill O, Sokol E, Liu G, Pavlick D, et al. Molecular determinants of response to PD-L1 blockade across tumor types. Nat Commun. 2021 Jun 25;12(1):3969. http://dx.doi.org/10.1038/s41467-021-24112-w