22 november 2022: lees ook dit artikel: https://kanker-actueel.nl/NL/operatieve-verwijdering-van-uitzaaiingen-vanuit-nierkanker-zorgt-voor-een-jarenlange-levensverlenging-van-3-tot-12-jaar-in-vergelijking-met-geen-operatie.html

22 november 2022: Bron: PLATINUM PRIORITY – KIDNEY CANCER EDITORIAL BY XXX ON PP. X–Y OF THIS ISSUE

De resultaten van overall overleving waren uitstekend na eerst een operatie waarbij zoveel mogelijk tumorweefsel of de volledig aangetaste nier wordt verwijderd (cytoreductieve nefrectomie) bij patiënten met uitgezaaide gevorderde nierkanker en daarna behandeld met immuuntherapie met anti-PD medicijnen (checkpointremmers) (ICI) of een gerichte therapie.
De cytoreductieve nefrectomie (CN) resulteerde in een statistisch significant betere algehele overleving in zowel de ICI (HR, 0,61; P = 0,013) als gerichte therapie groepen in vergelijking met geen cytoreductieve nefrectomie. (HR, 0,72; P < 0,001). 
Er was geen verschil in het totale overlevingsvoordeel van CN tussen de ICI- en gerichte therapiegroepen zelf (interactie P = 0,60).

Op basis van deze resultaten, schrijven de onderzoekers, moet vooraf cytoreductieve nefrectomie (CN) nog steeds worden overwogen bij nauwkeurig geselecteerde patiënten (met gunstig of gemiddeld risico) die in aanmerking komen voor immuuntherapie met anti-PD medicijnen (checkpointremmers) (ICI).

Het volledige studierapport is gepubliceerd in European Urology en tegen betaling in te zien of te downloaden. Klik op de titel van het abstract:

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

Published:October 19, 2022DOI:https://doi.org/10.1016/j.eururo.2022.10.004

Abstract

Background

The role of upfront cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) in the era of immune checkpoint inhibitors is unclear.

Objective

To evaluate the relationship between upfront CN and clinical outcomes in the setting of mRCC treated with immune checkpoint inhibitors or targeted therapy.

Design, setting, and participants

Using the International Metastatic RCC Database Consortium, we retrospectively identified patients diagnosed with de novo mRCC treated with immune checkpoint inhibitors or targeted therapy.

Outcome measurements and statistical analysis

Overall survival (OS) was compared between the two groups using the Kaplan-Meier method and multivariable Cox regressions adjusting for known prognostic factors.

Results and limitations

We identified a total of 4639 eligible patients with mRCC. Among the 4202 patients treated with targeted therapy and 437 patients treated with immune checkpoint inhibitors, 2326 (55%) and 234 (54%) patients received upfront CN prior to treatment start. In multivariable analyses, CN was associated with significantly better OS in both the immune checkpoint inhibitor–treated (hazard ratio : 0.61; 95% confidence interval , 0.41–0.90, p = 0.013) and the targeted therapy treatment (HR: 0.72; 95% CI, 0.67–0.78, p < 0.001) group. There was no difference in OS benefit of CN between the immune checkpoint inhibitor and targeted therapy treatment groups (interaction p = 0.6). Limitations include selection of patients from large academic centers and the retrospective nature of the study.

Conclusions

Upfront CN is associated with a significant OS benefit in selected patients treated by either immune checkpoint inhibitors or targeted therapy, and still has a role in selected patients in the era of immune checkpoint inhibitors.

Patient summary

Before effective systemic therapies were available for metastatic kidney cancer, surgical removal of the primary (kidney) tumor was the mainstay of treatment. The role of removing the primary tumor has recently been called into question given that more effective systemic therapies have become available. In this study, we find that removal of the primary kidney tumor still has a benefit for selected patients treated with highly effective modern systemic therapies, including targeted therapies and immune checkpoint inhibitors.

References

    • Larcher A.
    • Wallis C.J.D.
    • Bex A.
    • et al.
    Individualised indications for cytoreductive nephrectomy: which criteria define the optimal candidates?.
    Eur Urol Oncol. 2019; 2: 365-378
    View in Article 
    • 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
    View in Article 
    • Mickisch G.H.J
    • 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: 966-970https://doi.org/10.1016/s0140-6736(01)06103-7
    View in Article 
    • Bhindi B.
    • Graham J.
    • Wells J.C.
    • et al.
    Deferred cytoreductive nephrectomy in patients with newly diagnosed metastatic renal cell carcinoma.
    Eur Urol. 2020; 78: 615-623
    View in Article 
    • Escudier B.
    • Porta C.
    • Schmidinger M.
    • et al.
    Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up.
    Ann Oncol. 2019; 30: 706-720
    View in Article 
    • 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
    View in Article 
    • Méjean A.
    • Ravaud A.
    • Thezenas S.
    • 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
    View in Article 
    • Hanna N.
    • Sun M.
    • Meyer C.P.
    • 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: 3267-3275
    View in Article 
    • Heng D.Y.C.
    • Wells J.C.
    • Rini B.I.
    • 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: 704-710
    View in Article 
    • Choueiri T.K.
    • 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: 60-66
    View in Article 
    • Rini B.I.
    • Powles T.
    • Atkins M.B.
    • et al.
    Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial.
    Lancet. 2019; 393: 2404-2415
    View in Article 
    • Motzer R.J.
    • Penkov K.
    • Haanen J.
    • et al.
    Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma.
    N Engl J Med. 2019; 380: 1103-1115
    View in Article 
    • Choueiri T.K.
    • Powles T.
    • Burotto M.
    • et al.
    Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma.
    N Engl J Med. 2021; 384: 829-841
    View in Article 
    • Motzer R.
    • Alekseev B.
    • Rha S.-Y.
    • et al.
    Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma.
    N Engl J Med. 2021; 384: 1289-1300
    View in Article 
    • Motzer R.J.
    • Tannir N.M.
    • McDermott D.F.
    • et al.
    Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma.
    N Engl J Med. 2018; 378: 1277-1290
    View in Article 
    • von Elm E.
    • Altman D.G.
    • Egger M.
    • Pocock S.J.
    • Gøtzsche P.C.
    • Vandenbroucke J.P.
    The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.
    J Clin Epidemiol. 2008; 61: 344-349
    View in Article 
    • Miettinen O.S.
    Stratification by a multivariate confounder score.
    Am J Epidemiol. 1976; 104: 609-620
    View in Article 

  18. Greifer N. cobalt: Covariate balance tables and plots. 2019. https://ngreifer.github.io/cobalt/.

    View in Article 

  19. Greifer N. WeightIt: weighting for covariate balance in observational studies. 2019. https://ngreifer.github.io/WeightIt/reference/index.html.

    View in Article 
    • McIntosh A.G.
    • Umbreit E.C.
    • Holland L.C.
    • et al.
    Optimizing patient selection for cytoreductive nephrectomy based on outcomes in the contemporary era of systemic therapy.
    Cancer. 2020; 126: 3950-3960
    View in Article 
    • Bex A.
    • Albiges L.
    • Ljungberg B.
    • et al.
    Updated European Association of Urology guidelines for cytoreductive nephrectomy in patients with synchronous metastatic clear-cell renal cell carcinoma.
    Eur Urol. 2018; 74: 805-809
    View in Article 
    • Motzer R.J.
    • Russo P.
    Cytoreductive nephrectomy—patient selection is key.
    N Engl J Med. 2018; 379: 481-482
    View in Article 
    • Roussel E.
    • Verbiest A.
    • Milenkovic U.
    • et al.
    Too good for CARMENA: criteria associated with long systemic therapy free intervals post cytoreductive nephrectomy for metastatic clear cell renal cell carcinoma.
    Scand J Urol. 2020; 54: 493-499
    View in Article 
    • Fujikawa K.
    • Matsui Y.
    • Oka H.
    • Fukuzawa S.
    • Takeuchi H.
    Serum C-reactive protein level and the impact of cytoreductive surgery in patients with metastatic renal cell carcinoma.
    J Urol. 1999; 162: 1934-1937
    View in Article 
    • Dadian G.
    • Riches P.G.
    • Henderson D.C.
    • et al.
    Immunological parameters in peripheral blood of patients with renal cell carcinoma before and after nephrectomy.
    Br J Urol. 1994; 74: 15-22
    View in Article 
    • Flanigan R.C.
    Debulking nephrectomy in metastatic renal cancer.
    Clin Cancer Res. 2004; 10: 6335S-6341S
    View in Article 
    • Lahn M.
    • Fisch P.
    • Köhler G.
    • et al.
    Pro-inflammatory and T cell inhibitory cytokines are secreted at high levels in tumor cell cultures of human renal cell carcinoma.
    Eur Urol. 1999; 35: 70-80
    View in Article 
    • Marcus S.G.
    • Choyke P.L.
    • Reiter R.
    • et al.
    Regression of metastatic renal cell carcinoma after cytoreductive nephrectomy.
    J Urol. 1993; 150: 463-466
    View in Article 
    • Singla N.
    • Hutchinson R.C.
    • Ghandour R.A.
    • 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
    View in Article 
    • Ghatalia P.
    • Handorf E.A.
    • Deng M.
    • et al.
    Role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC).
    J Clin Oncol. 2021; 39: 4582
    View in Article 
    • De Velasco G.
    • Alonso-Gordoa T.
    • Rodríguez-Moreno J.F.
    • et al.
    676P CABOPRE: a phase II study of cabozantinib (cabo) prior cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC).
    Ann Oncol. 2021; 32: S698-S699
    View in Article 

  32. Fristrup N. Deferred cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma: the NORDIC-SUN-Trial (NORDIC-SUN). https://clinicaltrials.gov/ct2/show/NCT03977571.

    View in Article 
    • Vaishampayan U.N.
    • Tangen C.
    • Tripathi A.
    • et al.
    SWOG S1931 (PROBE): phase III randomized trial of immune checkpoint inhibitor (ICI) combination regimen with or without cytoreductive nephrectomy (CN) in advanced renal cancer.
    J Clin Oncol. 2022; 40: TPS402
    View in Article 

  34. Southwest Oncology Group. Comparing the outcome of immunotherapy-based drug combination therapy with or without surgery to remove the kidney in metastatic kidney cancer, the PROBE trial. (PROBE). https://clinicaltrials.gov/ct2/show/NCT04510597.

    View in Article 
    • Lalani A.-K.-A.
    • Swaminath A.
    • Pond G.R.
    • et al.
    Phase II trial of cytoreductive stereotactic hypofractionated radiotherapy with combination ipilimumab/nivolumab for metastatic kidney cancer (CYTOSHRINK).
    J Clin Oncol. 2020; 38: TPS761
    View in Article 

  36. Ontario Clinical Oncology Group (OCOG). SBRT with combination ipilimumab/nivolumab for metastatic kidney cancer (CYTOSHRINK). https://clinicaltrials.gov/ct2/show/NCT04090710.

    View in Article 

Article Info

Publication History

Published online: October 19, 2022
Accepted: October 4, 2022
Associate Editor: Sarah P. Psutka

Publication stage

In Press Corrected Proof

Identification

DOI: https://doi.org/10.1016/j.eururo.2022.10.004

Copyright

© 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.

ScienceDirect

Access this article on ScienceDirect

Linked Article

uitgezaaide nierkanker, gerichte therapie, immuuntherapie, checkpointremmers, anti-PD medicijnen, nefrectomie, overall overleving


Plaats een reactie ...

Reageer op "Eerst nier verwijderen en daarna behandelen met immuuntherapie of gerichte therapie geeft betere overall overleving bij patienten met uitgezaaide gevorderde nierkanker dan zonder nefrectomie"


Gerelateerde artikelen
 

Gerelateerde artikelen

Eerst nier verwijderen en >> Operatieve verwijdering van >>