Skip to main content
Erschienen in: Targeted Oncology 6/2018

15.10.2018 | Systematic Review

Should CARMENA Really Change our Attitude Towards Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma? A Systematic Review and Meta-Analysis Evaluating Cytoreductive Nephrectomy in the Era of Targeted Therapy

verfasst von: Francesco Massari, Vincenzo Di Nunno, Lidia Gatto, Matteo Santoni, Riccardo Schiavina, Laura Cosmai, Eugenio Brunocilla, Andrea Ardizzoni, Camillo Porta

Erschienen in: Targeted Oncology | Ausgabe 6/2018

Einloggen, um Zugang zu erhalten

Abstract

Background

Cytoreductive nephrectomy in metastatic renal cell carcinoma (mRCC) patients has been common clinical practice due to evidence that resection of the primary tumor results in a survival benefit regardless of systemic treatment. Recently, the first large phase III randomized, non-inferiority prospective clinical trial evaluating this surgical approach demonstrated that systemic treatment alone was not inferior to primary surgery plus systemic treatment.

Objective

Our aim was to evaluate if cytoreductive nephrectomy results in a survival benefit over systemic treatment alone in patients with mRCC and in specific subgroups, including patients with brain metastases, poor performance status, poor prognosis according to IMDC or MSKCC criteria, and clear cell and non-clear cell histologies.

Patients and Methods

We identified 16 published studies providing complete data for the comparison between cytoreductive nephrectomy + systemic treatment versus systemic treatment alone, and selected 9 for subgroup analysis. The inverse variance technique was applied for the meta-analysis of hazard ratios (HR), and, due to the intrinsic heterogeneity of the data, we adopted a random effects model. Risk of bias among the studies was estimated by the Newcastle-Ottawa Scale (NOS).

Results

Our analysis suggested a survival benefit for patients receiving cytoreductive nephrectomy (pooled HR of 0.48, 95% confidence interval of 0.42–0.56) in the overall population. Survival advantages were also observed in patients with clear cell and non-clear renal cell carcinoma, while no benefit was evident in patients with brain metastasis, poor performance status, and poor risk.

Conclusion

Cytoreductive nephrectomy seems to result in a survival benefit in both clear cell and non-clear cell histology, while no survival advantage was found in patients with specific clinical features. Despite a high level of heterogeneity, our results highlight the importance of a good selection of patients to whom a primary surgical approach could be proposed.
Literatur
1.
Zurück zum Zitat Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.CrossRef Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.CrossRef
2.
Zurück zum Zitat 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.CrossRef 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.CrossRef
3.
Zurück zum Zitat Mickisch GH, Garin A, Van PH, 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.CrossRef Mickisch GH, Garin A, Van PH, 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.CrossRef
4.
Zurück zum Zitat 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.CrossRef 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.CrossRef
5.
Zurück zum Zitat 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(1):60–6.CrossRef 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(1):60–6.CrossRef
6.
Zurück zum Zitat 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(4):704–10.CrossRef 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(4):704–10.CrossRef
7.
Zurück zum Zitat Mathieu R, Pignot G, Ingles A, 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(8):339.e9–15.CrossRef Mathieu R, Pignot G, Ingles A, 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(8):339.e9–15.CrossRef
8.
Zurück zum Zitat Bamias A, Tzannis K, Papatsoris A, et al. Prognostic significance of cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma treated with first-line sunitinib: a European multiinstitutional study. Clin Genitourin Cancer. 2014;12(5):373–83.CrossRef Bamias A, Tzannis K, Papatsoris A, et al. Prognostic significance of cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma treated with first-line sunitinib: a European multiinstitutional study. Clin Genitourin Cancer. 2014;12(5):373–83.CrossRef
9.
Zurück zum Zitat Xiao WJ, Zhu Y, Dai B, Zhang HL, Ye DW. Assessment of survival of patients with metastatic clear cell renal cell carcinoma after radical cytoreductive nephrectomy versus no surgery: a seer analysis. Int Braz J Urol. 2015;41(2):288–95.CrossRef Xiao WJ, Zhu Y, Dai B, Zhang HL, Ye DW. Assessment of survival of patients with metastatic clear cell renal cell carcinoma after radical cytoreductive nephrectomy versus no surgery: a seer analysis. Int Braz J Urol. 2015;41(2):288–95.CrossRef
10.
Zurück zum Zitat 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(5):2405–11.PubMed 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(5):2405–11.PubMed
11.
Zurück zum Zitat Warren M, Venner PM, North S, et al. A population-based study examining the effect of tyrosine kinase inhibitors on survival in metastatic renal cell carcinoma in Alberta and the role of nephrectomy prior to treatment. Can Urol Assoc J. 2009;3(4):281–9.CrossRef Warren M, Venner PM, North S, et al. A population-based study examining the effect of tyrosine kinase inhibitors on survival in metastatic renal cell carcinoma in Alberta and the role of nephrectomy prior to treatment. Can Urol Assoc J. 2009;3(4):281–9.CrossRef
12.
Zurück zum Zitat 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(11):1291–7.CrossRef 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(11):1291–7.CrossRef
13.
Zurück zum Zitat Vaishampayan U, Vankayala H, Vigneau FD, et al. The impact of targeted therapy on overall survival in advanced renal cancer: a study of the National Surveillance Epidemiology and end results registry database. Clin Genitourin Cancer. 2014;12(2):124–9.CrossRef Vaishampayan U, Vankayala H, Vigneau FD, et al. The impact of targeted therapy on overall survival in advanced renal cancer: a study of the National Surveillance Epidemiology and end results registry database. Clin Genitourin Cancer. 2014;12(2):124–9.CrossRef
14.
Zurück zum Zitat 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(5b):E67–74.CrossRef 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(5b):E67–74.CrossRef
15.
Zurück zum Zitat 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(1):96–102.CrossRef 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(1):96–102.CrossRef
16.
Zurück zum Zitat 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(9):2245–52.CrossRef 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(9):2245–52.CrossRef
17.
Zurück zum Zitat 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(8):736–40.CrossRef 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(8):736–40.CrossRef
19.
Zurück zum Zitat Graham J, Wells C, Donskov F, et al. Cytoreductive nephrectomy in metastatic papillary renal cell carcinoma: results from the international metastatic renal cell carcinoma database consortium (IMDC). J Clin Oncol. 2018;36(suppl_6):581.CrossRef Graham J, Wells C, Donskov F, et al. Cytoreductive nephrectomy in metastatic papillary renal cell carcinoma: results from the international metastatic renal cell carcinoma database consortium (IMDC). J Clin Oncol. 2018;36(suppl_6):581.CrossRef
22.
Zurück zum Zitat Petrelli F, Coinu A, Vavassori I, et al. Cytoreductive nephrectomy in metastatic renal cell carcinoma treated with targeted therapies: a systematic review with a meta-analysis. Clin Genitourin Cancer. 2016;14(6):465–72.CrossRef Petrelli F, Coinu A, Vavassori I, et al. Cytoreductive nephrectomy in metastatic renal cell carcinoma treated with targeted therapies: a systematic review with a meta-analysis. Clin Genitourin Cancer. 2016;14(6):465–72.CrossRef
23.
Zurück zum Zitat García-Perdomo HA, Zapata-Copete JA, Castillo-Cobaleda DF. Role of cytoreductive nephrectomy in the targeted therapy era: a systematic review and meta-analysis. Investig Clin Urol. 2018;59(1):2–9.CrossRef García-Perdomo HA, Zapata-Copete JA, Castillo-Cobaleda DF. Role of cytoreductive nephrectomy in the targeted therapy era: a systematic review and meta-analysis. Investig Clin Urol. 2018;59(1):2–9.CrossRef
24.
Zurück zum Zitat Motzer RJ, Russo P. Cytoreductive nephrectomy - patient selection is key. N Engl J Med. 2018;379(5):481–2.CrossRef Motzer RJ, Russo P. Cytoreductive nephrectomy - patient selection is key. N Engl J Med. 2018;379(5):481–2.CrossRef
26.
Zurück zum Zitat Staehler M, Haseke N, Khoder W, Stief CG. Profile of temsirolimus in the treatment of advanced renal cell carcinoma. Onco Targets Ther. 2010;3:191–6.CrossRef Staehler M, Haseke N, Khoder W, Stief CG. Profile of temsirolimus in the treatment of advanced renal cell carcinoma. Onco Targets Ther. 2010;3:191–6.CrossRef
27.
Zurück zum Zitat Iacovelli R, De Giorgi U, Galli L, Zucali P, Nolè F, et al. Is it possible to improve prognostic classification in patients affected by metastatic renal cell carcinoma with an intermediate or poor prognosis? Clin Genitourin Cancer. 2018. Iacovelli R, De Giorgi U, Galli L, Zucali P, Nolè F, et al. Is it possible to improve prognostic classification in patients affected by metastatic renal cell carcinoma with an intermediate or poor prognosis? Clin Genitourin Cancer. 2018.
28.
Zurück zum Zitat Bex A, Mulders P, Jewett MAS, Wagstaff J, van Velthoven R, et al. Immediate versus deferred cytoreductive nephrectomy (CN) in patients with synchronous metastatic renal cell carcinoma (mRCC) receiving sunitinib (EORTC 30073 SURTIME). Ann Oncol. 2017;28(suppl_5):v605–49.CrossRef Bex A, Mulders P, Jewett MAS, Wagstaff J, van Velthoven R, et al. Immediate versus deferred cytoreductive nephrectomy (CN) in patients with synchronous metastatic renal cell carcinoma (mRCC) receiving sunitinib (EORTC 30073 SURTIME). Ann Oncol. 2017;28(suppl_5):v605–49.CrossRef
29.
Zurück zum Zitat Durinck S, Stawiski EW, Pavía-Jiménez A, et al. Spectrum of diverse genomic alterations define non-clear cell renal carcinoma subtypes. Nat Genet. 2015;47(1):13–21.CrossRef Durinck S, Stawiski EW, Pavía-Jiménez A, et al. Spectrum of diverse genomic alterations define non-clear cell renal carcinoma subtypes. Nat Genet. 2015;47(1):13–21.CrossRef
30.
Zurück zum Zitat Cancer Genome Atlas Research Network. Comprehensive molecular characterization of papillary renal-cell carcinoma. N Engl J Med. 2016;374(2):135–45.CrossRef Cancer Genome Atlas Research Network. Comprehensive molecular characterization of papillary renal-cell carcinoma. N Engl J Med. 2016;374(2):135–45.CrossRef
31.
Zurück zum Zitat Cancer Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013;499(7456):43–9.CrossRef Cancer Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013;499(7456):43–9.CrossRef
32.
Zurück zum Zitat Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus Everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803–13.CrossRef Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus Everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803–13.CrossRef
33.
Zurück zum Zitat Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277–90.CrossRef Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277–90.CrossRef
Metadaten
Titel
Should CARMENA Really Change our Attitude Towards Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma? A Systematic Review and Meta-Analysis Evaluating Cytoreductive Nephrectomy in the Era of Targeted Therapy
verfasst von
Francesco Massari
Vincenzo Di Nunno
Lidia Gatto
Matteo Santoni
Riccardo Schiavina
Laura Cosmai
Eugenio Brunocilla
Andrea Ardizzoni
Camillo Porta
Publikationsdatum
15.10.2018
Verlag
Springer International Publishing
Erschienen in
Targeted Oncology / Ausgabe 6/2018
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-018-0601-2

Weitere Artikel der Ausgabe 6/2018

Targeted Oncology 6/2018 Zur Ausgabe

Acknowledgement to Referees

Acknowledgement to Referees

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.