Renal cell carcinoma, Adjuvant immunotherapy, Recurrence after immunotherapy, immunotherapy resistance, Treatment sequencing
References
1. Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, et al. Overall Ssurvival with adjuvant pembrolizumab in renal-cell carcinoma. N Engl J Med. 2024 Apr 18;390(15):1359–71. https://doi.org/10.1056/NEJMoa2312695
2. Ciccarese C, Strusi A, Arduini D, Russo P, Palermo G, Foschi N, et al. Post nephrectomy management of localized renal cell carcinoma. From risk stratification to therapeutic evidence in an evolving clinical scenario [Internet]. Cancer Treat Rev [Internet]. 2023 Apr 1 [cited 2025 Nov 13];115. Available from: https://www.cancertreatmentreviews.com/article/S0305-7372(23)00019-1/fulltext
3. Ravaud A, Motzer RJ, Pandha HS, George DJ, Pantuck AJ, Patel A, et al. The New England Journal of Medicine. Massachusetts Medical Society; 2016 [cited 2025 Nov 13]. Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy [Internet]. New Engl J Med. (Massachusetts Medical Society); 2016 [cited 2025 Nov 13]. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa1611406. https://doi.org/10.1056/NEJMoa1611406
4. Motzer RJ, Haas NB, Donskov F, Gross-Goupil M, Varlamov S, Kopyltsov E, et al. Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with localized or locally advanced renal cell carcinoma [Internet]. J Clin Oncol [Internet]. 2017 Dec 10 [cited 2025 Nov 13].; Available from: https://ascopubs.org/doi/10.1200/JCO.2017.73.5324
5. Eisen T, Frangou E, Oza B, Ritchie AWS, Smith B, Kaplan R, et al. Adjuvant sorafenib for renal cell carcinoma at intermediate or high risk of relapse: Results Ffrom the SORCE randomized phase III Iintergroup trial. J Clin Oncol Off J Am Soc Clin Oncol. 2020 Dec 1;38(34):4064–75. https://doi.org/10.1200/JCO.20.01800
6. Ryan CW, Tangen CM, Heath EI, Stein MN, Meng MV, Alva AS, et al. Adjuvant everolimus after surgery for renal cell carcinoma (EVEREST): A double-blind, placebo-controlled, randomised, phase 3 trial. Lancet Lond Engl. 2023 Sept 23;402(10407):1043–51. https://doi.org/10.1016/S0140-6736(23)00913-3
7. Gross-Goupil M, Kwon TG, Eto M, Ye D, Miyake H, Seo SI, et al. Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: rResults from the phase III, randomized ATLAS trial. Ann OncolOff J EurSoc Med Oncol. 2018 Dec 1;29(12):2371–78. https://doi.org/10.1093/annonc/mdy454
8. Motzer RJ, Ravaud A, Patard JJ, Pandha HS, George DJ, Patel A, et al. Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results. Eur Urol. 2018 Jan;73(1):62–8. https://doi.org/10.1016/j.eururo.2017.09.008
9. Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Chang YH, et al. Adjuvant Ppembrolizumab after nephrectomy in renal-cell carcinoma. N Engl J Med. 2021 Aug 19;385(8):683–94.
10. Pal SK, Uzzo R, Karam JA, Master VA, Donskov F, Suarez C, et al. Adjuvant atezolizumab versus placebo for patients with renal cell carcinoma at increased risk of recurrence following resection (IMmotion 010): aA multicentre, randomised, double-blind, phase 3 trial. The Lancet. 2022 Oct 1;400(10358):1103–16. https://doi.org/10.1016/S0140-6736(22)01658-0
11. Motzer RJ, Russo P, Grünwald V, Tomita Y, Zurawski B, Parikh O, et al. Adjuvant nivolumab plus ipilimumab versus placebo for localised renal cell carcinoma after nephrectomy (check mate 914): aA double-blind, randomised, phase 3 trial. The Lancet. 2023 Mar 11;401(10379):821–32. https://doi.org/10.1016/S0140-6736(22)02574-0
12. Allaf ME, Kim SE, Master V, McDermott DF, Harshman LC, Cole SM, et al. Perioperative nivolumab versus observation in patients with renal cell carcinoma undergoing nephrectomy (PROSPER ECOG-ACRIN EA8143): aAn open-label, randomised, phase 3 study. Lancet Oncol. 2024 Aug 1;25(8):1038–52.
13. Staff TAP. PD-L1 plus CTLA-4 inhibition for renal cell carcinoma following resection: RAMPART [Internet]. 2025 [cited 2025 Nov 13]. Available from: https://ascopost.com/news/october-2025/pd-l1-plus-ctla-4-inhibition-for-renal-cell-carcinoma-following-resection-rampart/
14. Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Chang YH, et al. Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. N Engl J Med. 2021 Aug 19;385(8):683–94.
15. Patard JJ, Kim HL, Lam JS, Dorey FJ, Pantuck AJ, Zisman A, et al. Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: aAn international multicenter study. J Clin Oncol Off J Am Soc Clin Oncol. 2004 Aug 15;22(16):3316–22. https://doi.org/10.1200/JCO.2004.09.104
16. Parker WP, Cheville JC, Frank I, Zaid HB, Lohse CM, Boorjian SA, et al. Application of the stage, size, grade, and necrosis (SSIGN) score for clear cell renal cell carcinoma in contemporary patients. Eur Urol. 2017 Apr;71(4):665–73. https://doi.org/10.1016/j.eururo.2016.05.034
17. Scoring algorithm to predict survival after nephrectomy and immunotherapy in patients with metastatic renal cell carcinoma - – Leibovich - – 2003 - – Cancer - – Wiley Online Library [Internet]. [cited 2025 Nov 17]. Available from: https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.11851
18. Leibovich BC, Lohse CM, Cheville JC, Zaid HB, Boorjian SA, Frank I, et al. Predicting oncologic outcomes in renal cell carcinoma after surgery. Eur Urol. 2018 May;73(5):772–80. https://doi.org/10.1016/j.eururo.2018.01.005
19. Kluger HM, Tawbi HA, Ascierto ML, Bowden M, Callahan MK, Cha E, et al. Defining tumor resistance to PD-1 pathway blockade: recommendations from the first meeting of the SITC Immunotherapy Resistance Taskforce. J Immunother Cancer. 2020 Mar;8(1):e000398. https://doi.org/10.1136/jitc-2019-000398
20. Grünwald V, Bex A, Rottey S, Suárez C, Procopio G, Velasco G, et al. Current status of adjuvant immunotherapy and relapse management in renal cell carcinoma: Insights from a European Delphi study. Eur J Cancer. 2025 July25;225:115569. https://doi.org/10.1016/j.ejca.2025.115569
21. Alonso-Gordoa T, Anguera G, Domínguez-Esteban M, Reig Ò, Martínez-Barros H, Molina-Cerrillo J, et al. Expert consensus on patterns of progression in kidney cancer after adjuvant immunotherapy and subsequent treatment strategies. Cancer Treat Rev. 2025 May 1;136:102925. https://doi.org/10.1016/j.ctrv.2025.102925
22. Farber NJ, Kim CJ, Modi PK, Hon JD, Sadimin ET, Singer EA. Renal cell carcinoma: tThe search for a reliable biomarker. Transl Cancer Res. 2017 June;6(3):620–32. https://doi.org/10.21037/tcr.2017.05.19
23. Anderson AC, Ho J, Hall ET, Hannan R, Liao JJ, Louie AV, et al. Focal therapy for oligometastatic and oligoprogressive renal cell carcinoma: aA narrative review. Future Oncol (Lond Engl). 2024;20(33):2573–88. https://doi.org/10.1080/14796694.2024.2389769
24. Bekku K, Kawada T, Sekito T, Yoshinaga K, MaruyamaY, Yamanoi T, et al. The diagnosis and treatment approach for oligo-recurrent and oligo-progressive renal cell carcinoma. Cancers. 2023 Dec 17;15(24):5873. https://doi.org/10.3390/cancers15245873
25. Dason S, Lacuna K, Hannan R, Singer EA, Runcie K. State of the Aart: Multidisciplinary management of oligometastatic renal cell carcinoma. Am Soc Clin Oncol Educ Book [Internet]. 2023 May [cited 2025 Nov 22]; Available from: https://ascopubs.org/doi/10.1200/EDBK_390038. https://doi.org/10.1200/EDBK_390038
26. Tang C, Sherry AD, Seo A, Hara K, Choi H, Liu S, et al. Metastasis-directed radiotherapy without systemic therapy for oligometastatic clear-cell renal-cell carcinoma: pPrimary efficacy analysis of a single-arm, single-centre, phase 2 trial. Lancet Oncol. 2025 Oct 1;26(10):1289–99. https://doi.org/10.1016/S1470-2045(25)00380-8
27. Hannan R, Christensen M, Christie A, Garant A, Pedrosa I, Robles L, et al. Stereotactic ablative radiation for systemic therapy-naïve oligometastatic kidney cancer. Eur Urol Oncol. 2022 Dec;5(6):695–703. https://doi.org/10.1016/j.euo.2022.06.008
28. 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;6(5):100692. https://doi.org/10.1016/j.adro.2021.100692
29. Roviello G, Paolieri F, Catalano M, Galli L, Doni L, Peschiera F, et al. Adjuvant immunotherapy in high-risk renal cell carcinoma: Indications, limitations, and perspectives. A consensus statement from the GIOTTO Uro-Oncology Group. Crit Rev Oncol Hematol. 2025 Dec;216:104978. https://doi.org/10.1016/j.critrevonc.2025.104978
30. Bedke J, Ghanem YA, Albiges L, Bonn S, Campi R, Capitanio U, et al. Updated European Association of Urology Guidelines on the use of adjuvant immune checkpoint inhibitors and subsequent therapy for renal cell carcinoma. Eur Urol. 2025 Apr;87(4):491–6. https://doi.org/10.1016/j.eururo.2025.01.014
31. Zarif TE, Semaan K, Xie W, Eid M, Zarba M, Issa W, et al. First-line systemic therapy following adjuvant immunotherapy in renal cell carcinoma: An international multicenter study. Eur Urol. 2024 Dec 1;86(6):503–12. https://doi.org/10.1016/j.eururo.2024.07.016
32. Procopio G, Claps M, Pircher C, Porcu L, Sepe P, Guadalupi V, et al. A multicenter phase 2 single arm study of cabozantinib in patients with advanced or unresectable renal cell carcinoma pre-treated with one immune-checkpoint inhibitor: The BREAKPOINT trial (Meet-Uro trial 03). Tumori. 2023 Feb;109(1):129–37. https://doi.org/10.1177/03008916221138881
33. Albiges L, Powles T, Sharma A, et al. CaboPoint: A Phase 2 Study of Second-line Cabozantinib After Checkpoint Inhibitor-based Combination Therapy in Patients with Metastatic Renal Cell Carcinoma. Eur Urol. 2026;89(3):210-219. doi:10.1016/j.eururo.2025.07.018
34. 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. https://doi.org/10.1016/S1470-2045(19)30513-3
35. Choueiri TK, Albiges L, Barthélémy P, Iacovelli R, Emambux S, Molina-Cerrillo J, et al. Tivozanib plus nivolumab versus tivozanib monotherapy in patients with renal cell carcinoma following an immune checkpoint inhibitor: rResults of the phase 3 TiNivo-2 Sstudy. The Lancet. 2024 Oct 5;404(10460):1309–20. https://doi.org/10.1016/S0140-6736(24)01758-6
36. Lee CH, Shah AY, Rasco D, Rao A, Taylor MH, Simone CD, et al. Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (Study 111/KEYNOTE-146): aA phase 1b/2 study. Lancet Oncol. 2021 July 1;22(7):946–58. https://doi.org/10.1016/S1470-2045(21)00241-2
37. Pal SK, Albiges L, Tomczak P, Suárez C, Voss MH, Velasco G de, et al. Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): aA multicentre, randomised, open-label, phase 3 trial. The Lancet. 2023 July 15;402(10397):185–95. https://doi.org/10.1016/S0140-6736(23)00922-4
38. McKay RR, Leucht K, Xie W, Jegede O, Braun DA, Atkins MB, et al. A pooled analysis of 3 Pphase II trials of salvage nivolumab/ipilimumab after nivolumab in renal cell carcinoma. The Oncologist. 2024 Apr 1;29(4):324–31. https://doi.org/10.1093/oncolo/oyad298
39. Sackstein P, Atkins MB. How should we approach salvage therapy in advanced renal cell carcinoma after first-line immunotherapy combinations? Expert Opin Biol Ther. 2025 Mar 4;25(3):205–8. https://doi.org/10.1080/14712598.2025.2459193
40. Choueiri TK, Powles T, Peltola K, Velasco G de, Burotto M, Suarez C, et al. Belzutifan versus everolimus for advanced renal-cell carcinoma. N Engl J Med. 2024 Aug 21;391(8):710–21. https://doi.org/10.1056/NEJMoa2313906
41. Choueiri TK, Merchan JR, Figlin R, McDermott DF, Arrowsmith E, Michaelson MD, et al. Belzutifan plus cabozantinib as first-line treatment for patients with advanced clear-cell renal cell carcinoma (LITESPARK-003): aAn open-label, single-arm, phase 2 study. Lancet Oncol. 2025 Jan 1;26(1):64–73. https://doi.org/10.1016/S1470-2045(24)00649-1
42. Bex A, Ghanem YA, Albiges L, Bonn S, Campi R, Capitanio U, et al. European Association of Urology Guidelines on renal cell carcinoma: The 2025 Uupdate. Eur Urol. 2025 June 1;87(6):683–96. https://doi.org/10.1016/j.eururo.2025.02.020
43. Shah AY, Kotecha RR, Lemke EA, Chandramohan A, Chaim JL, Msaouel P, et al. Outcomes of patients with metastatic clear-cell renal cell carcinoma treated with second-line VEGFR-TKI after first-line immune checkpoint inhibitors. Eur J Cancer. 2019;114:67-75. doi:10.1016/j.ejca.2019.04.003
44. Sazuka T, Matsushita Y, Sato H, Osawa T, Hinata N, Hatakeyama S, et al. Efficacy and safety of second-line cabozantinib after immuno-oncology combination therapy for advanced renal cell carcinoma: Japanese multicenter retrospective study. Sci Rep. 2023 Nov 23;13(1):20629. https://doi.org/10.1038/s41598-023-48087-4
45. Shah NJ, Sura S, Shinde R, Shi J, Bupathi M, Vickery D, et al. Real-world treatment patterns and clinical outcomes among patients with metastatic renal cell carcinoma post-immune-oncology and vascular endothelial growth factor receptor targeted therapies. Cancers. 2025 Apr 25;17(9):1434. https://doi.org/10.3390/cancers17091434
46. Chakiryan NH, Jiang DD, Gillis KA, Green E, Hajiran A, Hugar L, et al. Real-world survival outcomes associated with first-line immunotherapy, targeted therapy, and combination therapy for metastatic clear cell renal cell carcinoma. JAMA Netw Open. 2021 May 25;4(5):e2111329. https://doi.org/10.1001/jamanetworkopen.2021.11329
47. Shin SJ, Lee JL, Kwon TG, Shim BY, Chung HS, Kim SH, et al. Real-world study evaluating safety and effectiveness of axitinib in Korean patients with renal cell carcinoma after failure of one prior systemic therapy. Cancer Res Treat. 2023 Apr;55(2):643–51. https://doi.org/10.4143/crt.2022.883
48. Jakobsson M, Strambi A, Nilsson F, Arpegård J, Dalén J. Real-world experience of second-line axitinib in metastatic renal cell carcinoma: Analysis of the Swedish population. Future Oncol. 2024 June 23;20(20):1385–92. https://doi.org/10.1080/14796694.2024.2351352
49. Lai GS, Li JR, Wang SS, Chen CS, Yang CK, Lin CY, et al. Real world treatment sequences and outcomes for metastatic renal cell carcinoma. PLoS One. 2023 Nov 22;18(11):e0294039. https://doi.org/10.1371/journal.pone.0294039
50. Waddell T, Pillai M, Armitage K, Graham DM, Moran M, Dilleen M, et al. Real-world effectiveness of first- and second-line anti-angiogenesis therapy in RCC: Analysis of a UK-based population. Future Oncol. 20(33):2547–58. https://doi.org/10.1080/14796694.2024.2385882
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