Cytoreductive nephrectomy for synchronous metastatic renal cell carcinoma. Is there enough evidence?


Submitted: September 4, 2022
Accepted: October 2, 2022
Published: December 28, 2022
Abstract Views: 609
PDF: 336
Supplementary Material: 37
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Authors

Objective: To assess the role of Cytoreductive Nephrectomy for synchronous metastatic Renal Cell Carcinoma patients in the Systemic Therapy era and beyond regarding the Overall Survival, the optimal sequence between Systemic Therapy and Cytoreductive Nephrectomy and prognostic factors.
Methods: The systematic review was conducted in accordance with the PRISMA guidelines. Bibliographic search was performed in Medline (PubMed), ClinicalTrials.gov, and Cochrane Library-Cochrane Central Register of Controlled Trials (CENTRAL). Studies included were those indexed from 2005 in an attempt to limit those conducted in the cytokine era. Risk of bias assessment was performed by two authors (K.S and T.L) using the Cochrane Collaborative Risk of Bias tool for randomized trials, the Cochrane Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for nonrandomized studies.
Results: Cytoreductive nephrectomy was associated with improved overall survival in all but one of the observational studies. While in all of these studies the unvariable analysis showed improved overall survival in favor of the cytoreductive nephrectomy group in some studies the subgroup analysis showed no benefit. Regarding the optimal sequence, deferred cytoreductive nephrectomy demonstrated better results in more studies than upfront cytoreductive nephrectomy but a advantage was not clearly certain. In the analysis of possible prognostic factors for overall survival with cytoreductive nephrectomy, most common prognostic factors found were age (in 8 studies), tumor histology (in 7 studies), number of metastasis (in 6 studies), and T stage.
Conclusions: Cytoreductive nephrectomy can still play an important role in wisely selected patients, although the role of cytoreductive nephrectomy in the new immunotherapy era needs to be defined.


Flanigan RC, Salmon SE, Blumenstein BA, et al. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001; 345:1655-9. DOI: https://doi.org/10.1056/NEJMoa003013

Mickisch GH, Garin A, van Poppel H, et al. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet. 2001; 358:966-70. DOI: https://doi.org/10.1016/S0140-6736(01)06103-7

Flanigan RC, Mickisch G, Sylvester R, et al. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis.J Urol. 2004; 171:1071-6. DOI: https://doi.org/10.1097/01.ju.0000110610.61545.ae

Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007; 356:115-24. DOI: https://doi.org/10.1056/NEJMoa065044

Coppin C, Le L, Porzsolt F, Wilt T. Targeted therapy for advanced renal cell carcinoma. Cochrane Database Syst Rev. 2008:CD006017. DOI: https://doi.org/10.1002/14651858.CD006017.pub2

Méjean A, Ravaud A, Thezenas S, et al. Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma. N Engl J Med. 2018; 379:417-427.

Bex A, Mulders P, Jewett M, 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: https://doi.org/10.1001/jamaoncol.2018.5543

Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018; 378:1277-1290. DOI: https://doi.org/10.1056/NEJMoa1712126

Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019; 380:1116-1127. DOI: https://doi.org/10.1056/NEJMoa1816714

Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med.2019; 380:1103-1115. DOI: https://doi.org/10.1056/NEJMoa1816047

Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009; 62:1006-1012. DOI: https://doi.org/10.1016/j.jclinepi.2009.06.005

Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011; 343:d5928 DOI: https://doi.org/10.1136/bmj.d5928

Sterne JA, Hernan MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 2016; 355:i4919. DOI: https://doi.org/10.1136/bmj.i4919

Conti SL, Thomas IC, Hagedorn JC, et al. Utilization of cytoreductive nephrectomy and patient survival in the targeted therapy era. Int J Cancer. 2014; 134:2245-52. DOI: https://doi.org/10.1002/ijc.28553

Aizer AA, Urun Y, McKay RR, et al. Cytoreductive nephrectomy in patients with metastatic non-clear-cell renal cell carcinoma (RCC). BJU Int. 2014; 113:E67-74. DOI: https://doi.org/10.1111/bju.12442

Abern MR, Scosyrev E, Tsivian M, et al. Survival of patients undergoing cytoreductive surgery for metastatic renal cell carcinoma in the targeted-therapy era. Anticancer Res. 2014; 34:2405-11.

Vaishampayan U, George J, Vigneau F. Predictors of Cytoreductive Nephrectomy for Metastatic Kidney Cancer in SEER and Metropolitan Detroit Databases. J Kidney Cancer VHL. 2019; 6:13-25. DOI: https://doi.org/10.15586/jkcvhl.2019.121

Zhao Z, Wu W, Duan X, et al. The value of cytoreductive nephrectomy on the survival of metastatic renal carcinoma patients based on the number of site-specific metastases. PLoS One. 2019;14:e0215861. DOI: https://doi.org/10.1371/journal.pone.0215861

Marchioni M, Bandini M, Preisser 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: https://doi.org/10.1016/j.euf.2017.11.012

Palumbo C, Mistretta FA, Knipper S, et al. Contemporary Cytoreductive Nephrectomy Provides Survival Benefit in Clear-cell Metastatic Renal Cell Carcinoma. Clin Genitourin Cancer. 2020; 18:e730-e738. DOI: https://doi.org/10.1016/j.clgc.2020.05.009

Luzzago S, Palumbo C, Rosiello G, 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: https://doi.org/10.1016/j.euf.2020.04.009

Alnimer Y, Qasrawi A, Yan D, Wang P. Prognostic Impact of Cytoreductive Nephrectomy in Patients with Metastatic Renal Cell Carcinoma: Data from a Large Population-Based Database. Urol J. 2021; 19:111-119

Hanna N, Sun M, Meyer CP, et al. Survival Analyses of Patients With Metastatic Renal Cancer Treated With Targeted Therapy With or Without Cytoreductive Nephrectomy: A National Cancer Data Base Study. J Clin Oncol. 2016; 34:3267-75. DOI: https://doi.org/10.1200/JCO.2016.66.7931

Singla N, Hutchinson RC, Ghandour RA, 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.e9-604.e17.25. DOI: https://doi.org/10.1016/j.urolonc.2020.02.029

Janisch F, Hillemacher T, Fuehner C, et al. The impact of cytoreductive nephrectomy on survival outcomes in patients treated with tyrosine kinase inhibitors for metastatic renal cell carcinoma in a real-world cohort. Urol Oncol. 2020; 38:739.e9-739.e15. DOI: https://doi.org/10.1016/j.urolonc.2020.04.033

You D, Jeong IG, Ahn JH, et al. The value of cytoreductive nephrectomy for metastatic renal cell carcinoma in the era of targeted therapy. J Urol. 2011; 185:54-9. DOI: https://doi.org/10.1016/j.juro.2010.09.018

Graham J, Wells JC, Donskov F, et al. Cytoreductive Nephrectomy in Metastatic Papillary Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium. Eur Urol Oncol. 2019; 2:643-648. DOI: https://doi.org/10.1016/j.euo.2019.03.007

Klatte T, Fife K, Welsh SJ, et al. Prognostic effect of cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma: a comparative study using inverse probability of treatment weighting. World J Urol. 2018; 36:417-425.

You D, Jeong IG, Song C, et al. 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: https://doi.org/10.1093/jjco/hyu171

Tatsugami K, Shinohara N, Kondo T, et al. Role of cytoreductive nephrectomy for Japanese patients with primary renal cell carcinoma in the cytokine and targeted therapy era. Int J Urol. 2015; 22:736-40. DOI: https://doi.org/10.1111/iju.12803

Day D, Kanjanapan Y, Kwan E, et al. Benefit from cytoreductive nephrectomy and the prognostic role of neutrophil-to-lymphocyte ratio in patients with metastatic renal cell carcinoma. Intern Med J. 2016; 46:1291-1297. DOI: https://doi.org/10.1111/imj.13202

Choueiri TK, Xie W, Kollmannsberger C, et al. The impact of cytoreductive nephrectomy on survival of patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor targeted therapy. J Urol. 2011; 185:60-6. DOI: https://doi.org/10.1016/j.juro.2010.09.012

Heng DY, 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. DOI: https://doi.org/10.1016/j.eururo.2014.05.034

de Groot S, Redekop WK, Sleijfer S, et al. Survival in Patients With Primary Metastatic Renal Cell Carcinoma Treated With Sunitinib With or Without Previous Cytoreductive Nephrectomy: Results From a Population-based Registry. Urology. 2016; 95:121-7. DOI: https://doi.org/10.1016/j.urology.2016.04.042

Poprach A, Holanek M, Chloupkova R, et al. Cytoreductive Nephrectomy and Overall Survival of Patients with Metastatic Renal Cell Carcinoma Treated with Targeted Therapy-Data from the National Renis Registry. Cancers (Basel). 2020; 12:2911. DOI: https://doi.org/10.3390/cancers12102911

Song Y, Du CX, Zhang W, et al. Impact of Cytoreductive Nephrectomy on Survival in Patients with Metastatic Renal Cell Carcinoma Treated by Targeted Therapy. Chin Med J (Engl). 2016; 129:530-5. DOI: https://doi.org/10.4103/0366-6999.177001

Bhindi B, Graham J, Wells JC, et al. Deferred Cytoreductive Nephrectomy in Patients with Newly Diagnosed Metastatic Renal Cell Carcinoma. Eur Urol. 2020; 78:615-623. DOI: https://doi.org/10.1016/j.eururo.2020.04.038

Patel MI, Beattie K, Bang A, et al. Cytoreductive nephrectomy for metastatic renal cell carcinoma: inequities in access exist despite

improved survival. Cancer Med. 2017; 6:2188-2193 DOI: https://doi.org/10.1002/cam4.1137

Cytoreductive Nephrectomy for Patients with Metastatic Renal Cell Carcinoma: Real World Data from Canadian Centers. Eur Urol Focus. 2021:S2405-4569(21)00276-5.

Méjean A, Ravaud A, Thezenas S, et al. Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma. N Engl J Med. 2018; 379:417-427. DOI: https://doi.org/10.1056/NEJMoa1803675

Bakouny Z, Xie W, Dudani S, et al. Cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (MRCC) treated with immune checkpoint inhibitors (ICI) or targeted therapy (TT): A propensity score-based analysis. Journal of Clinical Oncology 2020; 38(6_suppl): 608-608. DOI: https://doi.org/10.1200/JCO.2020.38.6_suppl.608

Wood CG, Margulis V. Neoadjuvant (presurgical) therapy for renal cell carcinoma: a new treatment paradigm for locally advanced and metastatic disease. Cancer. 2009; 115(10 Suppl):2355-60. DOI: https://doi.org/10.1002/cncr.24240

Stroup SP, Raheem OA, Palazzi KL, 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; 81:805-11. DOI: https://doi.org/10.1016/j.urology.2012.10.054

Macleod LC, Odisho AY, Tykodi SS, et al. Comparative Effectiveness of Initial Surgery vs Initial Systemic Therapy for Metastatic Kidney Cancer in the Targeted Therapy Era: Analysis of a Population-based Cohort. Urology. 2018; 113:146-152. DOI: https://doi.org/10.1016/j.urology.2017.11.014

Bhindi B, Habermann EB, Mason RJ, et al. Comparative Survival following Initial Cytoreductive Nephrectomy versus Initial Targeted Therapy for Metastatic Renal Cell Carcinoma. J Urol. 2018; 200:528-534. DOI: https://doi.org/10.1016/j.juro.2018.03.077

Kapoor A, Wong ECL, Fang W, Wong NC. Upfront cytoreductive nephrectomy vs. upfront systemic therapy in metastatic kidney cancer. Can Urol Assoc J. 2019; 13:E377-E381.

de Bruijn R, Wimalasingham A, Szabados B, et al. Deferred Cytoreductive Nephrectomy Following Presurgical Vascular Endothelial Growth Factor Receptor-targeted Therapy in Patients with Primary Metastatic Clear Cell Renal Cell Carcinoma: A Pooled Analysis of Prospective Trial Data. Eur Urol Oncol. 2020; 3:168-173. DOI: https://doi.org/10.1016/j.euo.2019.12.004

Abel EJ, Spiess PE, Margulis V, et al. Cytoreductive Nephrectomy for Renal Cell Carcinoma with Venous Tumor Thrombus. J Urol. 2017; 198:281-288. DOI: https://doi.org/10.1016/j.juro.2017.03.011

dashek JJ, Zhang Y, Skelton WP 4th, et al. Dissecting Outcomes: Should Cytoreductive Nephrectomy Be Performed for Patients With Metastatic Renal Cell Carcinoma With Sarcomatoid Dedifferentiation? Front Oncol. 2021; 10:627025. DOI: https://doi.org/10.3389/fonc.2020.627025

Corcoran AT, Kaffenberger SD, Clark PE, et al. Hypoalbuminaemia is associated with mortality in patients undergoing cytoreductive nephrectomy. BJU Int. 2015; 116:351-7. DOI: https://doi.org/10.1111/bju.12897

Culp SH, Tannir NM, Abel EJ, et al. Can we better select patients with metastatic renal cell carcinoma for cytoreductive nephrectomy? Cancer. 2010; 116:3378-88. DOI: https://doi.org/10.1002/cncr.25046

Culp SH, Karam JA, Wood CG. Population-based analysis of factors associated with survival in patients undergoing cytoreductive nephrectomy in the targeted therapy era. Urol Oncol. 2014; 32:561-8. DOI: https://doi.org/10.1016/j.urolonc.2013.12.003

Kalogirou C, Mulfinger P, Sokolakis I, et al. Preoperative CReactive Protein Values as a Potential Component in Outcome Prediction Models of Metastasized Renal Cell Carcinoma Patients Receiving Cytoreductive Nephrectomy. Urol Int. 2017; 99:297-307. DOI: https://doi.org/10.1159/000475932

Kapoor A, Wong ECL, Fang W, Wong NC. Upfront cytoreductive nephrectomy vs. upfront systemic therapy in metastatic kidney cancer. Can Urol Assoc J. 2019; 13:E377-E381. DOI: https://doi.org/10.5489/cuaj.5666

Klatte T, Fife K, Welsh SJ, et al. Prognostic effect of cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma: a comparative study using inverse probability of treatment weighting. World J Urol. 2018; 36:417-425. DOI: https://doi.org/10.1007/s00345-017-2154-x

Ljungberg B, Sundqvist P, Lindblad P, et al. 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: https://doi.org/10.1080/21681805.2020.1815833

McIntosh AG, Umbreit EC, Holland LC, et al. Optimizing patient selection for cytoreductive nephrectomy based on outcomes in the contemporary era of systemic therapy. Cancer. 2020; 126:3950-3960. DOI: https://doi.org/10.1002/cncr.32991

Rosiello G, Knipper S, Palumbo C, et al. Unmarried status is a barrier for access to treatment in patients with metastatic renal cell

carcinoma. Int Urol Nephrol. 2019; 51:2181-2188. DOI: https://doi.org/10.1007/s11255-019-02266-3

Sharma P, Zargar-Shoshtari K, Caracciolo JT, et al. Sarcopenia as a predictor of overall survival after cytoreductive nephrectomy for metastatic renal cell carcinoma. Urol Oncol. 2015; 33:339.e17-23. DOI: https://doi.org/10.1016/j.urolonc.2015.01.011

Sakai I, Miyake H, Hinata N, Fujisawa M. Improved survival in patients with metastatic renal cell carcinoma undergoing cytoreductive nephrectomy in the era of targeted therapy. Int J Clin Oncol. 2014; 19:674-8. DOI: https://doi.org/10.1007/s10147-013-0612-z

Teishima J, Ohara S, Shinmei S, et al. Normalization of C-reactive protein levels following cytoreductive nephrectomy in patients

with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors is associated with improved overall survival. Urol Oncol. 2018; 36:339.e9-339.e15. DOI: https://doi.org/10.1016/j.urolonc.2018.04.008

Motzer RJ, Bacik J, Schwartz LH, et al. Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol. 2004; 22:454-63. DOI: https://doi.org/10.1200/JCO.2004.06.132

Westerman ME, Shapiro DD, Tannir NM, et al. Survival following cytoreductive nephrectomy: a comparison of existing prognostic models. BJU Int. 2020; 126:745-753. DOI: https://doi.org/10.1111/bju.15160

Uprety D, Bista A, Smith AL, et al. Cytoreductive Nephrectomy in Elderly Patients with Metastatic Renal Cell Carcinoma in the Targeted Therapy Era. Anticancer Res. 2018; 38:3013-3018. DOI: https://doi.org/10.21873/anticanres.12555

Katsimperis, S., Tzelves, L., Bellos, T., Pikramenos, K., Manolitsis, I., Tsikopoulos, I., & Mitsogiannis, I. (2022). Cytoreductive nephrectomy for synchronous metastatic renal cell carcinoma. Is there enough evidence?. Archivio Italiano Di Urologia E Andrologia, 94(4), 476–485. https://doi.org/10.4081/aiua.2022.4.476

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