The role of cytoreductive nephrectomy in metastatic renal cell carcinoma (RCC) has been studied intensively over the past few decades. Interestingly, the opinion with regard to the importance of this procedure has switched from a recommendation as a standard of care to an almost complete refutation. However, no definitive agreement on cytoreductive nephrectomy, including the pros and cons of the procedure, has been reached, and the topic remains highly controversial. With the advent of immune checkpoint inhibitors, we have experienced a paradigm shift, with immunotherapy playing a crucial role in the treatment algorithm. Nevertheless, obtaining results from prospective clinical trials on the role of cytoreductive nephrectomy requires time, and once some data have been gathered, the standards of systemic therapy may be different, and we stand again at the beginning. This review summarizes current knowledge on the topic in the light of newly evolving treatment strategies. The crucial point is to recognize who could be an appropriate candidate for immediate cytoreductive surgery that may facilitate the effect of systemic therapy through tumor debulking, or who might benefit from deferred cytoreduction in the setting of an objective response of the tumor. The role of prognostic factors in management decisions as well as the technical details associated with performing the procedure from a urological perspective are discussed. Ongoing clinical trials that may bring new evidence for transforming therapeutic paradigms are listed.

Department of Oncology Faculty of Medicine and Dentistry University Hospital Olomouc Palacky University 771 47 Olomouc Czech Republic

Department of Urology Faculty of Medicine and Dentistry University Hospital Olomouc Palacky University 771 47 Olomouc Czech Republic

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Capitanio U., Bensalah K., Bex A., Boorjian S.A., Bray F., Coleman J., Gore J.L., Sun M., Wood C., Russo P. Epidemiology of Renal Cell Carcinoma. Eur. Urol. 2019;75:74–84. doi: 10.1016/j.eururo.2018.08.036. PubMed DOI PMC

Siegel R.L., Miller K.D., Fuchs H.E., Jemal A. Cancer statistics, 2022. CA Cancer J. Clin. 2022;72:7–33. doi: 10.3322/caac.21708. PubMed DOI

George D.J., Lee C.H., Heng D. New approaches to first-line treatment of advanced renal cell carcinoma. Ther. Adv. Med. Oncol. 2021;13:17588359211034708. doi: 10.1177/17588359211034708. PubMed DOI PMC

Larcher A., Fallara G., Rosiello G., Re C., Baiamonte G., Agnesi S., Cignoli D., Colandrea G., Basile G., Briganti A., et al. Cytoreductive Nephrectomy in Metastatic Patients with Signs or Symptoms: Implications for Renal Cell Carcinoma Guidelines. Eur. Urol. 2020;78:321–326. doi: 10.1016/j.eururo.2020.05.014. PubMed DOI

Lapeyre-Prost A., Terme M., Pernot S., Pointet A.L., Voron T., Tartour E., Taieb J. Immunomodulatory Activity of VEGF in Cancer. Int. Rev. Cell Mol. Biol. 2017;330:295–342. doi: 10.1016/bs.ircmb.2016.09.007. PubMed DOI

Papaccio F., Della Corte C.M., Viscardi G., Di Liello R., Esposito G., Sparano F., Ciardiello F., Morgillo F. HGF/MET and the Immune System: Relevance for Cancer Immunotherapy. Int. J. Mol. Sci. 2018;19:3595. doi: 10.3390/ijms19113595. PubMed DOI PMC

Flanigan R.C., Salmon S.E., Blumenstein B.A., Bearman S.I., Roy V., McGrath P.C., Caton J.R., Munshi N., Crawford E.D. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. New Engl. J. Med. 2001;345:1655–1659. doi: 10.1056/NEJMoa003013. PubMed DOI

Mickisch G.H.J., Garin A., van Poppel H., de Prijck L., Sylvester R. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: A randomised trial. Lancet. 2001;358:966–970. doi: 10.1016/S0140-6736(01)06103-7. PubMed DOI

Flanigan R.C., Mickisch G., Sylvester R., Tangen C., Van Poppel H., Crawford E.D. Cytoreductive nephrectomy in patients with metastatic renal cancer: A combined analysis. J. Urol. 2004;171:1071–1076. doi: 10.1097/01.ju.0000110610.61545.ae. PubMed DOI

Motzer R.J., Hutson T.E., Tomczak P., Michaelson M.D., Bukowski R.M., Rixe O., Oudard S., Negrier S., Szcylik C., Kim S.T., et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. New Engl. J. Med. 2007;356:115–124. doi: 10.1056/NEJMoa065044. PubMed DOI

Escudier B., Eisen T., Stadler W.M., Szczylik C., Oudard S., Siebels M., Negrier S., Chevreau C., Solska E., Desai A.A., et al. Sorafenib in advanced clear-cell renal-cell carcinoma. New Engl. J. Med. 2007;356:125–134. doi: 10.1056/NEJMoa060655. PubMed DOI

Escudier B., Bellmunt J., Negrier S., Bajetta E., Melichar B., Bracarda S., Ravaud A., Golding S., Jethwa S., Sneller V. 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;28:2144–2150. doi: 10.1200/JCO.2009.26.7849. PubMed DOI

Hudes G., Carducci M., Tomczak P., Dutcher J., Figlin R., Kapoor A., Staroslawska E., Sosman J., McDermott D., Bodrogi I., et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N. Engl. J. Med. 2007;356:2271–2281. doi: 10.1056/NEJMoa066838. PubMed DOI

Rini B.I., Halabi S., Rosenberg J.E., Stadler W.M., Vaena D.A., Archer L., Atkins J.N., Picus J., Czaykowski P., Dutcher J., et al. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: Final results of CALGB 90206. J. Clin. Oncol. 2010;28:2137–2143. doi: 10.1200/JCO.2009.26.5561. PubMed DOI PMC

Sternberg C.N., Davis I.D., Mardiak J., Szcylik C., Lee E., Wagstaff J., Barrios C.H., Salman P., Gladkov O.A., Karvina A., et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: Results of a randomized phase III trial. J. Clin. Oncol. 2010;28:1061–1068. doi: 10.1200/JCO.2009.23.9764. PubMed DOI

Choueiri T.K., Xie W., Kollmannsberger C., North S., Knox J.J., Lampard J.G., McDermott D.F., Rini B.I., Heng D.Y. The impact of cytoreductive nephrectomy on survival of patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor targeted therapy. J. Urol. 2011;185:60–66. doi: 10.1016/j.juro.2010.09.012. PubMed DOI

Bhindi B., Abel E.J., Albiges L., Bensalah K., Boorjian S.A., Daneshmand S., Karam J.A., Mason R.J., Powles T., Bex A. Systematic Review of the Role of Cytoreductive Nephrectomy in the Targeted Therapy Era and Beyond: An Individualized Approach to Metastatic Renal Cell Carcinoma. Eur. Urol. 2019;75:111–128. doi: 10.1016/j.eururo.2018.09.016. PubMed DOI

Mejean A., Ravaud A., Thezenas S., Colas S., Beauval J.B., Bensalah K., Geoffrois L., Thiery-Vuillemin A., Cormier L., Lang H., et al. Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma. New Engl. J. Med. 2018;379:417–427. doi: 10.1056/NEJMoa1803675. PubMed DOI

Arora S., Sood A., Dalela D., Tang H.J., Patel A., Keeley J., Trinh Q.D., Rogers C.G., Menon M., Abdollah F. Cytoreductive Nephrectomy: Assessing the Generalizability of the CARMENA Trial to Real-World National Cancer Data Base Cases. Eur. Urol. 2019;75:352–353. doi: 10.1016/j.eururo.2018.10.054. PubMed DOI

Méjean A., Ravaud A., Thezenas S., Chevreau C., Bensalah K., Geoffrois L., Thiery-Vuillemin A., Cormier L., Lang H., Guy L., et al. Sunitinib Alone or after Nephrectomy for Patients with Metastatic Renal Cell Carcinoma: Is There Still a Role for Cytoreductive Nephrectomy? Eur. Urol. 2021;80:417–424. doi: 10.1016/j.eururo.2021.06.009. PubMed DOI

Kutikov A., Uzzo R.G., Caraway A., Reese C.T., Egleston B.L., Chen D.Y., Viterbo R., Greenberg R.E., Wong Y.N., Raman J.D., et al. Use of systemic therapy and factors affecting survival for patients undergoing cytoreductive nephrectomy. BJU Int. 2010;106:218–223. doi: 10.1111/j.1464-410X.2009.09079.x. PubMed DOI PMC

Dariane C., Timsit M.O., Méjean A. Position of cytoreductive nephrectomy in the setting of metastatic renal cell carcinoma patients: Does the CARMENA trial lead to a paradigm shift? Bull Cancer. 2018;105((Suppl. 3)):S229–S234. doi: 10.1016/S0007-4551(18)30377-1. PubMed DOI

Bex A., Mulders P., Jewett M., Wagstaff J., van Thienen J.V., Blank C.U., van Velthoven R., Del Pilar Laguna M., Wood L., van Melick H.H.E., et al. Comparison of Immediate vs Deferred Cytoreductive Nephrectomy in Patients with Synchronous Metastatic Renal Cell Carcinoma Receiving Sunitinib: The SURTIME Randomized Clinical Trial. JAMA Oncol. 2019;5:164–170. doi: 10.1001/jamaoncol.2018.5543. PubMed DOI PMC

Motzer R.J., Tannir N.M., McDermott D.F., Aren Frontera O., Melichar B., Choueiri T.K., Plimack E.R., Barthelemy P., Porta C., George S., et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N. Engl. J. Med. 2018;378:1277–1290. doi: 10.1056/NEJMoa1712126. PubMed DOI PMC

Motzer R., Rini B.I., McDermott D.F., Frontera O.A., Hammers H.J., Carducci M.A., Salman P., Escudier B., Beuselinck B., Amin A., et al. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: Extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol. 2019;20:1370–1385. doi: 10.1016/S1470-2045(19)30413-9. PubMed DOI PMC

Choueiri T.K., Powles T., Burotto M., Escudier B., Bourlon M.T., Zurawski B., Juarez V.M.O., Hsieh J.J., Basso U., Shah A.Y., et al. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. New Engl. J. Med. 2021;384:829–841. doi: 10.1056/NEJMoa2026982. PubMed DOI PMC

Motzer R.J., Powles T., Burotto M., Escudier B., Bourlon M.T., Shah A.Y., Suárez C., Hamzaj A., Porta C., Hocking C.M., et al. Nivolumab plus cabozantinib versus sunitinib in first-line treatment for advanced renal cell carcinoma (CheckMate 9ER): Long-term follow-up results from an open-label, randomised, phase 3 trial. Lancet Oncol. 2022;23:888–898. doi: 10.1016/S1470-2045(22)00290-X. PubMed DOI PMC

Motzer R., Alekseev B., Rha S.Y., Porta C., Eto M., Powles T., Grünwald V., Hutson T.E., Kopyltsov E., Méndez-Vidal M.J., et al. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N. Engl. J. Med. 2021;384:1289–1300. doi: 10.1056/NEJMoa2035716. PubMed DOI

Rini B.I., Plimack E.R., Stus V., Gafanov R., Hawkins R., Nosov D., Pouliot F., Alekseev B., Soulieres D., Melichar B., et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N. Engl. J. Med. 2019;380:1116–1127. doi: 10.1056/NEJMoa1816714. PubMed DOI

Powles T., Plimack E.R., Soulières D., Waddell T., Stus V., Gafanov R., Nosov D., Pouliot F., Melichar B., Vynnychenko I., et al. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): Extended follow-up from a randomised, open-label, phase 3 trial. Lancet Oncol. 2020;21:1563–1573. doi: 10.1016/S1470-2045(20)30436-8. PubMed DOI

Motzer R.J., Penkov K., Haanen J., Rini B., Albiges L., Campbell M.T., Venugopal B., Kollmannsberger C., Negrier S., Uemura M., et al. Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. New Engl. J. Med. 2019;380:1103–1115. doi: 10.1056/NEJMoa1816047. PubMed DOI PMC

Choueiri T.K., Motzer R.J., Rini B.I., Haanen J., Campbell M.T., Venugopal B., Kollmannsberger C., Gravis-Mescam G., Uemura M., Lee J.L., et al. Updated efficacy results from the JAVELIN Renal 101 trial: First-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma. Ann. Oncol. 2020;31:1030–1039. doi: 10.1016/j.annonc.2020.04.010. PubMed DOI PMC

Motzer R.J., Escudier B., McDermott D.F., Arén Frontera O., Melichar B., Powles T., Donskov F., Plimack E.R., Barthélémy P., Hammers H.J., et al. Survival outcomes and independent response assessment with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma: 42-month follow-up of a randomized phase 3 clinical trial. J. Immunother. Cancer. 2020;8 doi: 10.1136/jitc-2020-000891. PubMed DOI PMC

Au L., Hatipoglu E., Robert de Massy M., Litchfield K., Beattie G., Rowan A., Schnidrig D., Thompson R., Byrne F., Horswell S., et al. Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma. Cancer Cell. 2021;39:1497–1518.e1411. doi: 10.1016/j.ccell.2021.10.001. PubMed DOI PMC

Derosa L., Routy B., Fidelle M., Iebba V., Alla L., Pasolli E., Segata N., Desnoyer A., Pietrantonio F., Ferrere G., et al. Gut Bacteria Composition Drives Primary Resistance to Cancer Immunotherapy in Renal Cell Carcinoma Patients. Eur. Urol. 2020;78:195–206. doi: 10.1016/j.eururo.2020.04.044. PubMed DOI

Franzin R., Netti G.S., Spadaccino F., Porta C., Gesualdo L., Stallone G., Castellano G., Ranieri E. The Use of Immune Checkpoint Inhibitors in Oncology and the Occurrence of AKI: Where Do We Stand? Front. Immunol. 2020;11:574271. doi: 10.3389/fimmu.2020.574271. PubMed DOI PMC

Gan C.L., Dudani S., Heng D.Y.C. Prognostic and Predictive Factors in Metastatic Renal Cell Carcinoma: Current Perspective and a Look into the Future. Cancer J. 2020;26:365–375. doi: 10.1097/PPO.0000000000000468. PubMed DOI

Kuusk T., Abu-Ghanem Y., Mumtaz F., Powles T., Bex A. Perioperative therapy in renal cancer in the era of immune checkpoint inhibitor therapy. Curr. Opin. Urol. 2021;31:262–269. doi: 10.1097/MOU.0000000000000868. PubMed DOI

Gross E.E., Li M., Yin M., Orcutt D., Hussey D., Trott E., Holt S.K., Dwyer E.R., Kramer J., Oliva K., et al. A multicenter study assessing survival in patients with metastatic renal cell carcinoma receiving immune checkpoint inhibitor therapy with and without cytoreductive nephrectomy. Urol. Oncol. 2023;41:51.e25–51.e31. doi: 10.1016/j.urolonc.2022.08.013. PubMed DOI PMC

Esagian S.M., Ziogas I.A., Kosmidis D., Hossain M.D., Tannir N.M., Msaouel P. Long-Term Survival Outcomes of Cytoreductive Nephrectomy Combined with Targeted Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Individual Patient Data Meta-Analysis. Cancers. 2021;13:695. doi: 10.3390/cancers13040695. PubMed DOI PMC

Choi C.I., Kang M., Sung H.H., Jeon H.G., Jeong B.C., Jeon S.S., Lee H.M., Seo S.I.L. Oncologic Outcomes of Cytoreductive Nephrectomy in Synchronous Metastatic Renal-Cell Carcinoma: A Single-Center Experience. Clin. Genitourin. Cancer. 2018;16:e1189–e1199. doi: 10.1016/j.clgc.2018.07.030. PubMed DOI

Singla N., Ghandour R.A., Margulis V. Is cytoreductive nephrectomy relevant in the immunotherapy era? Curr. Opin. Urol. 2019;29:526–530. doi: 10.1097/MOU.0000000000000659. PubMed DOI

Singla N., Hakimi A.A., Margulis V. Editorial: The evolving role of cytoreductive nephrectomy. Curr. Opin. Urol. 2019;29:505–506. doi: 10.1097/MOU.0000000000000653. PubMed DOI

Singla N., Hutchinson R.C., Ghandour R.A., Freifeld Y., Fang D., Sagalowsky A.I., Lotan Y., Bagrodia A., Margulis V., Hammers H.J., et al. Improved survival after cytoreductive nephrectomy for metastatic renal cell carcinoma in the contemporary immunotherapy era: An analysis of the National Cancer Database. Urol. Oncol. 2020;38:604.e609–604.e617. doi: 10.1016/j.urolonc.2020.02.029. PubMed DOI PMC

Bakouny Z., El Zarif T., Dudani S., Connor Wells J., Gan C.L., Donskov F., Shapiro J., Davis I.D., Parnis F., Ravi P., et al. Upfront Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors or Targeted Therapy: An Observational Study from the International Metastatic Renal Cell Carcinoma Database Consortium. Eur. Urol. 2023;83:145–151. doi: 10.1016/j.eururo.2022.10.004. PubMed DOI

Pieretti A.C., Shapiro D.D., Westerman M.E., Hwang H., Wang X., Segarra L.A., Campbell M.T., Tannir N.M., Jonasch E., Matin S.F., et al. Tumor diameter response in patients with metastatic clear cell renal cell carcinoma is associated with overall survival. Urol. Oncol. 2021;39:837.e9–837.e17. doi: 10.1016/j.urolonc.2021.08.022. PubMed DOI PMC

Pignot G., Thiery-Vuillemin A., Albigès L., Walz J., Lang H., Balssa L., Parier B., Geoffrois L., Bensalah K., Schlürmann F., et al. Oncological Outcomes of Delayed Nephrectomy after Optimal Response to Immune Checkpoint Inhibitors for Metastatic Renal Cell Carcinoma. Eur. Urol. Oncol. 2022;5:577–584. doi: 10.1016/j.euo.2022.07.002. PubMed DOI

Rebuzzi S.E., Signori A., Banna G.L., Gandini A., Fornarini G., Damassi A., Maruzzo M., De Giorgi U., Basso U., Chiellino S., et al. The prognostic value of the previous nephrectomy in pretreated metastatic renal cell carcinoma receiving immunotherapy: A sub-analysis of the Meet-URO 15 study. J. Transl. Med. 2022;20:435. doi: 10.1186/s12967-022-03601-6. PubMed DOI PMC

Yoshino M., Ishihara H., Nemoto Y., Nakamura K., Nishimura K., Tachibana H., Fukuda H., Toki D., Yoshida K., Kobayashi H., et al. Therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. Jpn J. Clin. Oncol. 2022;52:1208–1214. doi: 10.1093/jjco/hyac099. PubMed DOI

Stellato M., Santini D., Verzoni E., De Giorgi U., Pantano F., Casadei C., Fornarini G., Maruzzo M., Sbrana A., Di Lorenzo G., et al. Impact of Previous Nephrectomy on Clinical Outcome of Metastatic Renal Carcinoma Treated with Immune-Oncology: A Real-World Study on Behalf of Meet-URO Group (MeetUro-7b) Front. Oncol. 2021;11:682449. doi: 10.3389/fonc.2021.682449. PubMed DOI PMC

Ghatalia P., Handorf E.A., Geynisman D.M., Deng M., Zibelman M.R., Abbosh P., Anari F., Greenberg R.E., Viterbo R., Chen D., et al. The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: A Real-World Multi-Institutional Analysis. J. Urol. 2022;208:71–79. doi: 10.1097/ju.0000000000002495. PubMed DOI PMC

Hahn A.W., Kotecha R.R., Viscuse P.V., Pieretti A.C., Wiele A.J., Jonasch E., Lee C.H., Gao J., Zurita A.J., Shah A.Y., et al. Cytoreductive Nephrectomy for Patients with Metastatic Sarcomatoid and/or Rhabdoid Renal Cell Carcinoma Treated with Immune Checkpoint Therapy. Eur. Urol. Focus. 2023 doi: 10.1016/j.euf.2023.02.008. PubMed DOI PMC

Kroeger N., Xie W., Lee J.L., Bjarnason G.A., Knox J.J., Mackenzie M.J., Wood L., Srinivas S., Vaishamayan U.N., Rha S.Y., 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. doi: 10.1002/cncr.28151. PubMed DOI PMC

Alevizakos M., Gaitanidis A., Nasioudis D., Msaouel P., Appleman L.J. Sarcomatoid Renal Cell Carcinoma: Population-Based Study of 879 Patients. Clin. Genitourin Cancer. 2019;17:e447–e453. doi: 10.1016/j.clgc.2019.01.005. PubMed DOI

Shuch B., Said J., La Rochelle J.C., Zhou Y., Li G., Klatte T., Kabbinaavar F.F., Pantuck A.J., Belldegrun A.S. Cytoreductive nephrectomy for kidney cancer with sarcomatoid histology--is up-front resection indicated and, if not, is it avoidable? J. Urol. 2009;182:2164–2171. doi: 10.1016/j.juro.2009.07.049. PubMed DOI PMC

Marchioni M., Bandini M., Preisser F., Tian Z., Kapoor A., Cindolo L., Primiceri G., Berardinelli F., Briganti A., Shariat S.F., et al. Survival after Cytoreductive Nephrectomy in Metastatic Non-clear Cell Renal Cell Carcinoma Patients: A Population-Based Study. Eur. Urol. Focus. 2019;5:488–496. doi: 10.1016/j.euf.2017.11.012. PubMed DOI

Aizer A.A., Urun Y., McKay R.R., Kibel A.S., Nguyen P.L., Choueiri T.K. Cytoreductive nephrectomy in patients with metastatic non-clear-cell renal cell carcinoma (RCC) BJU Int. 2014;113:E67–E74. doi: 10.1111/bju.12442. PubMed DOI PMC

Luzzago S., Palumbo C., Rosiello G., Knipper S., Pecoraro A., Mistretta F.A., Tian Z., Musi G., Montanari E., Soulières D., 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;7:598–607. doi: 10.1016/j.euf.2020.04.009. PubMed DOI

Kassouf W., Sanchez-Ortiz R., Tamboli P., Tannir N., Jonasch E., Merchant M.M., Matin S., Swanson D.A., Wood C.G. Cytoreductive nephrectomy for metastatic renal cell carcinoma with nonclear cell histology. J. Urol. 2007;178:1896–1900. doi: 10.1016/j.juro.2007.07.037. PubMed DOI

Riveros C., Ranganathan S., Xu J., Chang C., Kaushik D., Morgan M., Miles B.J., Muhammad T., Anis M., Aghazadeh M., et al. Comparative real-world survival outcomes of metastatic papillary and clear cell renal cell carcinoma treated with immunotherapy, targeted therapy, and combination therapy. Urol. Oncol. 2023;41:150.e151–150.e159. doi: 10.1016/j.urolonc.2022.11.022. PubMed DOI

Kyriakopoulos C.E., Chittoria N., Choueiri T.K., Kroeger N., Lee J.L., Srinivas S., Knox J.J., Bjarnason G.A., Ernst S.D., Wood L.A., et al. Outcome of patients with metastatic sarcomatoid renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium. Clin. Genitourin Cancer. 2015;13:e79–e85. doi: 10.1016/j.clgc.2014.08.011. PubMed DOI

de Velasco G., McKay R.R., Lin X., Moreira R.B., Simantov R., Choueiri T.K. Comprehensive Analysis of Survival Outcomes in Non-Clear Cell Renal Cell Carcinoma Patients Treated in Clinical Trials. Clin. Genitourin Cancer. 2017;15:652–660.e651. doi: 10.1016/j.clgc.2017.03.004. PubMed DOI

Adashek J.J., Zhang Y., Skelton W.P.t., Bilotta A., Chahoud J., Zemp L., Li J., Dhillon J., Manley B., Spiess P.E. Dissecting Outcomes: Should Cytoreductive Nephrectomy Be Performed for Patients with Metastatic Renal Cell Carcinoma with Sarcomatoid Dedifferentiation? Front. Oncol. 2020;10:627025. doi: 10.3389/fonc.2020.627025. PubMed DOI PMC

Blum K.A., Gupta S., Tickoo S.K., Chan T.A., Russo P., Motzer R.J., Karam J.A., Hakimi A.A. Sarcomatoid renal cell carcinoma: Biology, natural history and management. Nat. Rev. Urol. 2020;17:659–678. doi: 10.1038/s41585-020-00382-9. PubMed DOI PMC

Studentova H., Rusarova N., Ondruskova A., Zemankova A., Student V., Jr., Skanderova D., Melichar B. The Role of Cytoreductive Nephrectomy in Renal Cell Carcinoma with Sarcomatoid Histology: A Case Series and Review of the Literature. Curr. Oncol. 2022;29:5475–5488. doi: 10.3390/curroncol29080433. PubMed DOI PMC

Escudier B., Porta C., Schmidinger M., Rioux-Leclercq N., Bex A., Khoo V., Grünwald V., Gillessen S., Horwich A. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2019;30:706–720. doi: 10.1093/annonc/mdz056. PubMed DOI

Blick C., Bott S., Muneer A., Barber N.J., Hindley R., Eden C., Sullivan M. Laparoscopic cytoreductive nephrectomy: A three-center retrospective analysis. J. Endourol. 2010;24:1451–1455. doi: 10.1089/end.2009.0458. PubMed DOI

Chapin B.F., Delacroix S.E., Jr., Culp S.H., Nogueras Gonzalez G.M., Tannir N.M., Jonasch E., Tamboli P., Wood C.G. Safety of presurgical targeted therapy in the setting of metastatic renal cell carcinoma. Eur. Urol. 2011;60:964–971. doi: 10.1016/j.eururo.2011.05.032. PubMed DOI PMC

Palumbo C., Knipper S., Dzyuba-Negrean C., Pecoraro A., Rosiello G., Tian Z., Shariat S.F., Simeone C., Briganti A., Saad F., et al. Complication rates, failure to rescue and in-hospital mortality after cytoreductive nephrectomy in the older patients. J. Geriatr. Oncol. 2020;11:718–723. doi: 10.1016/j.jgo.2019.06.005. PubMed DOI

Takagi T., Sugihara T., Yasunaga H., Horiguchi H., Fushimi K., Kondo T., Homma Y., Tanabe K. Cytoreductive nephrectomy for metastatic renal cell carcinoma: A population-based analysis of perioperative outcomes according to clinical stage. Int. J. Urol. 2014;21:770–775. doi: 10.1111/iju.12446. PubMed DOI

Stroup S.P., Raheem O.A., Palazzi K.L., Liss M.A., Mehrazin R., Kopp R.P., Patel N., Cohen S.A., Park S.K., Patterson A.L., et al. Does timing of cytoreductive nephrectomy impact patient survival with metastatic renal cell carcinoma in the tyrosine kinase inhibitor era? A multi-institutional study. Urology. 2013;81:805–811. doi: 10.1016/j.urology.2012.10.054. PubMed DOI

Powles T., Sarwar N., Stockdale A., Sarker S.J., Boleti E., Protheroe A., Jones R., Chowdhury S., Peters J., Oades G., et al. Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer. JAMA Oncol. 2016;2:1303–1309. doi: 10.1001/jamaoncol.2016.1197. PubMed DOI

Wallis C.J., Bjarnason G., Byrne J., Cheung D.C., Hoffman A., Kulkarni G.S., Nathens A.B., Nam R.K., Satkunasivam R. Morbidity and Mortality of Radical Nephrectomy for Patients with Disseminated Cancer: An Analysis of the National Surgical Quality Improvement Program Database. Urology. 2016;95:95–102. doi: 10.1016/j.urology.2016.04.055. PubMed DOI

Gershman B., Moreira D.M., Boorjian S.A., Lohse C.M., Cheville J.C., Costello B.A., Leibovich B.C., Thompson R.H. Comprehensive Characterization of the Perioperative Morbidity of Cytoreductive Nephrectomy. Eur. Urol. 2016;69:84–91. doi: 10.1016/j.eururo.2015.05.022. PubMed DOI

Ohno Y., Nakashima J., Ohori M., Tanaka A., Hashimoto T., Gondo T., Hatano T., Tachibana M. Clinical variables for predicting metastatic renal cell carcinoma patients who might not benefit from cytoreductive nephrectomy: Neutrophil-to-lymphocyte ratio and performance status. Int. J. Clin. Oncol. 2014;19:139–145. doi: 10.1007/s10147-012-0514-5. PubMed DOI

Culp S.H., Tannir N.M., Abel E.J., Margulis V., Tamboli P., Matin S.F., Wood C.G. Can we better select patients with metastatic renal cell carcinoma for cytoreductive nephrectomy? Cancer. 2010;116:3378–3388. doi: 10.1002/cncr.25046. PubMed DOI

Culp S.H., Karam J.A., Wood C.G. Population-based analysis of factors associated with survival in patients undergoing cytoreductive nephrectomy in the targeted therapy era. Urol. Oncol. 2014;32:561–568. doi: 10.1016/j.urolonc.2013.12.003. PubMed DOI

McIntosh A.G., Umbreit E.C., Holland L.C., Gu C., Tannir N.M., Matin S.F., Karam J.A., Culp S.H., Wood C.G. Optimizing patient selection for cytoreductive nephrectomy based on outcomes in the contemporary era of systemic therapy. Cancer. 2020;126:3950–3960. doi: 10.1002/cncr.32991. PubMed DOI

Marchioni M., Kriegmair M., Heck M., Amiel T., Porpiglia F., Ceccucci E., Campi R., Minervini A., Mari A., Van Bruwaene S., et al. Development of a Novel Risk Score to Select the Optimal Candidate for Cytoreductive Nephrectomy among Patients with Metastatic Renal Cell Carcinoma. Results from a Multi-institutional Registry (REMARCC) Eur. Urol. Oncol. 2021;4:256–263. doi: 10.1016/j.euo.2020.12.010. PubMed DOI

Silagy A.W., Kotecha R.R., Weng S., Holmes A., Singla N., Mano R., Attalla K., Weiss K.L., DiNatale R.G., Patil S., et al. Evolving biological associations of upfront cytoreductive nephrectomy in metastatic renal cell carcinoma. Cancer. 2021;127:3946–3956. doi: 10.1002/cncr.33790. PubMed DOI PMC

Tappero S., Barletta F., Piccinelli M.L., Cano Garcia C., Incesu R.B., Morra S., Scheipner L., Tian Z., Parodi S., Dell’Oglio P., et al. The Association between Cytoreductive Nephrectomy and Overall Survival in Metastatic Renal Cell Carcinoma with Primary Tumor Size ≤4 cm. Eur. Urol. Focus. 2023 doi: 10.1016/j.euf.2023.02.010. PubMed DOI

Mazzone E., Nazzani S., Preisser F., Tian Z., Marchioni M., Bandini M., Capitanio U., Kapoor A., Tilki D., Montorsi F., et al. Partial nephrectomy seems to confer a survival benefit relative to radical nephrectomy in metastatic renal cell carcinoma. Cancer Epidemiol. 2018;56:118–125. doi: 10.1016/j.canep.2018.08.006. PubMed DOI

Lenis A.T., Salmasi A.H., Donin N.M., Faiena I., Johnson D.C., Drakaki A., Gollapudi K., Blumberg J., Belldegrun A.S., Pantuck A.J., et al. Trends in usage of cytoreductive partial nephrectomy and effect on overall survival in patients with metastatic renal cell carcinoma. Urol. Oncol. 2018;36:78.e21–78.e28. doi: 10.1016/j.urolonc.2017.09.030. PubMed DOI

Capitanio U., Zini L., Perrotte P., Shariat S.F., Jeldres C., Arjane P., Pharand D., Widmer H., Péloquin F., Montorsi F., et al. Cytoreductive partial nephrectomy does not undermine cancer control in metastatic renal cell carcinoma: A population-based study. Urology. 2008;72:1090–1095. doi: 10.1016/j.urology.2008.06.059. PubMed DOI

Hutterer G.C., Patard J.J., Colombel M., Belldegrun A.S., Pfister C., Guille F., Artibani W., Montorsi F., Pantuck A.J., Karakiewicz P.I. Cytoreductive nephron-sparing surgery does not appear to undermine disease-specific survival in patients with metastatic renal cell carcinoma. Cancer. 2007;110:2428–2433. doi: 10.1002/cncr.23054. PubMed DOI

Krambeck A.E., Leibovich B.C., Lohse C.M., Kwon E.D., Zincke H., Blute M.L. The role of nephron sparing surgery for metastatic (pM1) renal cell carcinoma. J. Urol. 2006;176:1990–1995. doi: 10.1016/j.juro.2006.07.015. discussion 1995. PubMed DOI

Chen J., He Q., Liu W., Li Y., Zhuang W. The Effect of Cytoreductive Partial Nephrectomy in Elderly Patients with Metastatic Renal Cell Carcinoma. Clin. Interv. Aging. 2020;15:431–439. doi: 10.2147/CIA.S243902. PubMed DOI PMC

Zlatev D.V., Ozambela M., Salari K., Wang Y., Mossanen M., Pucheril D., Ingham M.D., Chung B.I., Chang S.L. Trends and morbidity for minimally invasive versus open cytoreductive nephrectomy in the management of metastatic renal cell carcinoma. J. Clin. Oncol. 2018;36 doi: 10.1200/JCO.2018.36.6_suppl.632. DOI

Rabets J.C., Kaouk J., Fergany A., Finelli A., Gill I.S., Novick A.C. Laparoscopic versus open cytoreductive nephrectomy for metastatic renal cell carcinoma. Urology. 2004;64:930–934. doi: 10.1016/j.urology.2004.06.052. PubMed DOI

Eisenberg M.S., Meng M.V., Master V.A., Stoller M.L., Rini B.I., Carroll P.R., Kane C.J. Laparoscopic versus open cytoreductive nephrectomy in advanced renal-cell carcinoma. J. Endourol. 2006;20:504–508. doi: 10.1089/end.2006.20.504. PubMed DOI

Ganeshappa A., Sundaram C., Lerner M.A., Gardner T.A. Role of the laparoscopic approach to cytoreductive nephrectomy in metastatic renal-cell carcinoma: Does size matter? J. Endourol. 2010;24:1289–1292. doi: 10.1089/end.2009.0401. PubMed DOI

Matin S.F., Madsen L.T., Wood C.G. Laparoscopic cytoreductive nephrectomy: The M. D. Anderson Cancer Center experience. Urology. 2006;68:528–532. doi: 10.1016/j.urology.2006.03.076. PubMed DOI

Margulis V., Matin S.F., Tannir N., Tamboli P., Swanson D.A., Jonasch E., Wood C.G. Surgical morbidity associated with administration of targeted molecular therapies before cytoreductive nephrectomy or resection of locally recurrent renal cell carcinoma. J. Urol. 2008;180:94–98. doi: 10.1016/j.juro.2008.03.047. PubMed DOI

Jackson B.L., Fowler S., Williams S.T. Perioperative outcomes of cytoreductive nephrectomy in the UK in 2012. BJU Int. 2015;116:905–910. doi: 10.1111/bju.12890. PubMed DOI

Nunez Bragayrac L., Hoffmeyer J., Abbotoy D., Attwood K., Kauffman E., Spiess P., Wagner A., Schwaab T. Minimally invasive cytoreductive nephrectomy: A multi-institutional experience. World J. Urol. 2016;34:1651–1656. doi: 10.1007/s00345-016-1827-1. PubMed DOI

Zhao K., Kim E.H., Vetter J.M., Hsieh J.J., Venkatesh R., Bhayani S.B., Figenshau R.S. Laparoscopic cytoreductive nephrectomy is associated with significantly improved survival compared with open cytoreductive nephrectomy or targeted therapy alone. Mol. Clin. Oncol. 2020;13:71. doi: 10.3892/mco.2020.2141. PubMed DOI PMC

Abel E.J., Spiess P.E., Margulis V., Master V.A., Mann M., Zargar-Shoshtari K., Borregales L.D., Sexton W.J., Patil D., Matin S.F., et al. Cytoreductive Nephrectomy for Renal Cell Carcinoma with Venous Tumor Thrombus. J. Urol. 2017;198:281–288. doi: 10.1016/j.juro.2017.03.011. PubMed DOI

Miyake H., Sugiyama T., Aki R., Matsushita Y., Tamura K., Motoyama D., Ito T., Otsuka A. Oncological outcomes after cytoreductive nephrectomy for patients with metastatic renal cell carcinoma with inferior vena caval tumor thrombus. Int. J. Clin. Oncol. 2018;23:553–558. doi: 10.1007/s10147-017-1232-9. PubMed DOI

Kwon T., Lee J.L., You D., Jeong I.G., Song C., Ahn H., Kim C.S., Hong J.H. Impact of surgery on the prognosis of metastatic renal cell carcinoma with IVC thrombus received TKI therapy. J. Surg. Oncol. 2014;110:145–150. doi: 10.1002/jso.23612. PubMed DOI

Qi N., Wu P., Chen J., Li T., Ning X., Wang J., Gong K. Cytoreductive nephrectomy with thrombectomy before targeted therapy improves survival for metastatic renal cell carcinoma with venous tumor thrombus: A single-center experience. World J. Surg. Oncol. 2017;15:4. doi: 10.1186/s12957-016-1066-3. PubMed DOI PMC

Kroeger N., Pantuck A.J., Wells J.C., Lawrence N., Broom R., Kim J.J., Srinivas S., Yim J., Bjarnason G.A., Templeton A., et al. Characterizing the impact of lymph node metastases on the survival outcome for metastatic renal cell carcinoma patients treated with targeted therapies. Eur. Urol. 2015;68:506–515. doi: 10.1016/j.eururo.2014.11.054. PubMed DOI

Gershman B., Thompson R.H., Moreira D.M., Boorjian S.A., Lohse C.M., Costello B.A., Cheville J.C., Leibovich B.C. Lymph Node Dissection is Not Associated with Improved Survival among Patients Undergoing Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma: A Propensity Score Based Analysis. J. Urol. 2017;197:574–579. doi: 10.1016/j.juro.2016.09.074. PubMed DOI

Bhindi B., Wallis C.J.D., Boorjian S.A., Thompson R.H., Farrell A., Kim S.P., Karam J.A., Capitanio U., Golijanin D., Leibovich B.C., et al. The role of lymph node dissection in the management of renal cell carcinoma: A systematic review and meta-analysis. BJU Int. 2018;121:684–698. doi: 10.1111/bju.14127. PubMed DOI

Lughezzani G., Capitanio U., Jeldres C., Isbarn H., Shariat S.F., Arjane P., Widmer H., Perrotte P., Montorsi F., Karakiewicz P.I. Prognostic significance of lymph node invasion in patients with metastatic renal cell carcinoma: A population-based perspective. Cancer. 2009;115:5680–5687. doi: 10.1002/cncr.24682. PubMed DOI

Trinh Q.D., Sukumar S., Schmitges J., Bianchi M., Sun M., Shariat S.F., Sammon J.D., Jeldres C., Zorn K.C., Perrotte P., et al. Effect of nodal metastases on cancer-specific mortality after cytoreductive nephrectomy. Ann. Surg. Oncol. 2013;20:2096–2102. doi: 10.1245/s10434-012-2806-4. PubMed DOI

Labbate C., Hatogai K., Werntz R., Stadler W.M., Steinberg G.D., Eggener S., Sweis R.F. Complete response of renal cell carcinoma vena cava tumor thrombus to neoadjuvant immunotherapy. J. Immunother. Cancer. 2019;7:66. doi: 10.1186/s40425-019-0546-8. PubMed DOI PMC

Pignot G., Thiery-Vuillemin A., Walz J., Lang H., Bigot P., Werle P., Balssa L., Geoffrois L., Leblanc L., Albigès L., et al. Nephrectomy after Complete Response to Immune Checkpoint Inhibitors for Metastatic Renal Cell Carcinoma: A New Surgical Challenge? Eur. Urol. 2020;77:761–763. doi: 10.1016/j.eururo.2019.12.018. PubMed DOI

Gyorki D.E., Yuan J., Mu Z., Zaidi B., Pulitzer M., Busam K., Brady M.S., Coit D.G., Allison J.P., Wolchok J.D., et al. Immunological insights from patients undergoing surgery on ipilimumab for metastatic melanoma. Ann. Surg. Oncol. 2013;20:3106–3111. doi: 10.1245/s10434-013-2999-1. PubMed DOI PMC

Yanagisawa T., Schmidinger M., Kawada T., Bekku K., Kimura T., Shariat S.F. Radical Nephrectomy after Immune Checkpoint Inhibitors for Metastatic Renal Cell Carcinoma. Eur. Urol. Focus. 2023 doi: 10.1016/j.euf.2023.01.022. PubMed DOI

Graafland N.M., Szabados B., Tanabalan C., Kuusk T., Mumtaz F., Barod R., Nicol D., Boleti E., Powles T., Haanen J.B., et al. Surgical Safety of Deferred Cytoreductive Nephrectomy Following Pretreatment with Immune Checkpoint Inhibitor-Based Dual Combination Therapy. Eur. Urol. Oncol. 2022;5:373–374. doi: 10.1016/j.euo.2021.11.004. PubMed DOI

Singla N., Elias R., Ghandour R.A., Freifeld Y., Bowman I.A., Rapoport L., Enikeev M., Lohrey J., Woldu S.L., Gahan J.C., et al. Pathologic response and surgical outcomes in patients undergoing nephrectomy following receipt of immune checkpoint inhibitors for renal cell carcinoma. Urol. Oncol. 2019;37:924–931. doi: 10.1016/j.urolonc.2019.08.012. PubMed DOI PMC

You D., Jeong I.G., Song C., Lee J.L., Hong B., Hong J.H., Ahn H., Kim C.S. Analysis of pre-operative variables for identifying patients who might benefit from upfront cytoreductive nephrectomy for metastatic renal cell carcinoma in the targeted therapy era. Jpn J. Clin. Oncol. 2015;45:96–102. doi: 10.1093/jjco/hyu171. PubMed DOI

Fukuda H., Takagi T., Kondo T., Yoshida K., Shimizu S., Nagashima Y., Tanabe K. Prognostic value of the Glasgow Prognostic Score for patients with metastatic renal cell carcinoma treated by cytoreductive nephrectomy. Int. J. Clin. Oncol. 2018;23:539–546. doi: 10.1007/s10147-017-1221-z. PubMed DOI

Ljungberg B., Sundqvist P., Lindblad P., Kjellman A., Thorstenson A., Hellström M., Kröger Dahlin B.I., Thomasson M., Harmenberg U., Lundstam S. Survival advantage of upfront cytoreductive nephrectomy in patients with primary metastatic renal cell carcinoma compared with systemic and palliative treatments in a real-world setting. Scand. J. Urol. 2020;54:487–492. doi: 10.1080/21681805.2020.1815833. PubMed DOI

Conti S.L., Thomas I.C., Hagedorn J.C., Chung B.I., Chertow G.M., Wagner T.H., Brooks J.D., Srinivas S., Leppert J.T. Utilization of cytoreductive nephrectomy and patient survival in the targeted therapy era. Int. J. Cancer. 2014;134:2245–2252. doi: 10.1002/ijc.28553. PubMed DOI PMC

Mathieu R., Pignot G., Ingles A., Crepel M., Bigot P., Bernhard J.C., Joly F., Guy L., Ravaud A., Azzouzi A.R., et al. Nephrectomy improves overall survival in patients with metastatic renal cell carcinoma in cases of favorable MSKCC or ECOG prognostic features. Urol. Oncol. 2015;33:339.e9–339.e15. doi: 10.1016/j.urolonc.2015.05.014. PubMed DOI

Ljungberg B., Albiges L., Abu-Ghanem Y., Bedke J., Capitanio U., Dabestani S., Fernández-Pello S., Giles R.H., Hofmann F., Hora M., et al. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2022 Update. Eur. Urol. 2022;82:399–410. doi: 10.1016/j.eururo.2022.03.006. PubMed DOI

Motzer R.J., Jonasch E., Boyle S., Carlo M.I., Manley B., Agarwal N., Alva A., Beckermann K., Choueiri T.K., Costello B.A., et al. NCCN Guidelines Insights: Kidney Cancer, Version 1.2021. J. Natl. Compr. Canc. Netw. 2020;18:1160–1170. doi: 10.6004/jnccn.2020.0043. PubMed DOI PMC

Westerman M.E., Shapiro D.D., Wood C.G., Karam J.A. Neoadjuvant Therapy for Locally Advanced Renal Cell Carcinoma. Urol. Clin. N. Am. 2020;47:329–343. doi: 10.1016/j.ucl.2020.04.010. PubMed DOI

Rozeman E.A., Hoefsmit E.P., Reijers I.L.M., Saw R.P.M., Versluis J.M., Krijgsman O., Dimitriadis P., Sikorska K., van de Wiel B.A., Eriksson H., et al. Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma. Nat. Med. 2021;27:256–263. doi: 10.1038/s41591-020-01211-7. PubMed DOI

Navani V., Ernst M., Wells J.C., Yuasa T., Takemura K., Donskov F., Basappa N.S., Schmidt A., Pal S.K., Meza L., et al. Imaging Response to Contemporary Immuno-oncology Combination Therapies in Patients with Metastatic Renal Cell Carcinoma. JAMA Netw Open. 2022;5:e2216379. doi: 10.1001/jamanetworkopen.2022.16379. PubMed DOI PMC

Bell H., Cotta B.H., Salami S.S., Kim H., Vaishampayan U. “PROBE”ing the Role of Cytoreductive Nephrectomy in Advanced Renal Cancer. Kidney. Cancer J. 2022;6:3–9. doi: 10.3233/KCA-210010. PubMed DOI PMC

de Bruijn R.E., Kuusk T., Noe A.P., Blank C.U., Haanen J., Hendricksen K., Horenblas S., Bex A. Observation after Cytoreductive Nephrectomy in Patients with Synchronous Not Completely Resected Metastases of Renal Cell Carcinoma. Urology. 2017;109:127–133. doi: 10.1016/j.urology.2017.06.048. PubMed DOI

Albiges L., Tannir N.M., Burotto M., McDermott D., Plimack E.R., Barthélémy P., Porta C., Powles T., Donskov F., George S., et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: Extended 4-year follow-up of the phase III CheckMate 214 trial. ESMO Open. 2020;5:e001079. doi: 10.1136/esmoopen-2020-001079. PubMed DOI PMC

Albiges L., Rini B.I., Haanen J.B.A.G., Motzer R.J., Kollmannsberger C.K., Negrier S., Nole F., Bedke J., Bilen M.A., Nathan P., et al. 908PD—Primary renal tumour shrinkage in patients (pts) who did not undergo upfront cytoreductive nephrectomy (uCN): Subgroup analysis from the phase III JAVELIN Renal 101 trial of first-line avelumab + axitinib (A + Ax) vs sunitinib (S) for advanced renal cell carcinoma (aRCC) Ann. Oncol. 2019;30:v359–v360. doi: 10.1093/annonc/mdz249.007. DOI

Studentova H., Zemankova A., Spisarova M., Skanderova D., Tudos Z., Melichar B., Student V., Jr. A Pathological Complete Response to the Combination of Ipilimumab and Nivolumab in a Patient with Metastatic Renal Cell Carcinoma. Medicina. 2022;58:336. doi: 10.3390/medicina58030336. PubMed DOI PMC

Peak T.C., Fenu E.M., Rothberg M.B., Thomas C.Y., Davis R.L., Levine E.A. Pathologic Complete Response to Neoadjuvant Nivolumab/Ipilimumab in a Patient with Metastatic Renal Cell Carcinoma. Case Rep. Urol. 2020;2020:8846135. doi: 10.1155/2020/8846135. PubMed DOI PMC

Hagimoto H., Kashima S., Doi K., Nakayama S., Sano T., Imai S., Yasufuku T., Muramaki M., Yamada Y. Pathological complete response after nivolumab therapy following angiogenesis inhibitors in a patient with metastatic renal cell carcinoma. IJU Case Rep. 2020;3:287–290. doi: 10.1002/iju5.12220. PubMed DOI PMC

Cottrell T.R., Thompson E.D., Forde P.M., Stein J.E., Duffield A.S., Anagnostou V., Rekhtman N., Anders R.A., Cuda J.D., Illei P.B., et al. Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: A proposal for quantitative immune-related pathologic response criteria (irPRC) Ann. Oncol. 2018;29:1853–1860. doi: 10.1093/annonc/mdy218. PubMed DOI PMC

Real-World Impact of Upfront Cytoreductive Nephrectomy in Metastatic Non-Clear Cell Renal Cell Carcinoma Treated with First-Line Immunotherapy Combinations or Tyrosine Kinase Inhibitors (A Sub-Analysis from the ARON-1 Retrospective Study)