Zusammenfassung
Die Therapie des metastasierten Nierenkarzinoms hat in den letzten Jahren eine grundlegende Wandlung erfahren. Galt diese Entität früher als infaust und inoperabel, so gilt mittlerweile als gesichert, dass die Tumornephrektomie auch bei metastasierten Primärtumoren als urologisch-onkologischer Standard gilt, sofern im individuellen Fall vertretbar und technisch machbar. Auch die operative Entfernung von Metastasen, sofern eine komplette Resektion möglich ist, gilt als kurativer Ansatz. Ein besseres Verständnis der Prognosefaktoren erleichtert die Selektion von Patienten, die von einem systemischen Ansatz der Immunchemotherapie profitieren werden. Für rasch progrediente Fälle oder Patienten mit sarkomatoider Differenzierung stehen effektive Chemotherapien zur Verfügung. Angiogeneseinhibitoren wie Sutent, Avastin und Sorafenib bieten zukünftig eine effektive Erweiterung des therapeutischen Spektrums.
Abstract
The therapeutic regimen for metastatic renal cell cancer has changed substantially in the last years. Formerly, metastatic disease was regarded as being inoperable and had a disastrous prognosis. Nowadays, radical nephrectomy is the accepted urologic-oncologic standard therapy in metastatic primaries, if technically feasible. A complete resection of metastases may be curative, or can achieve a substantial palliative benefit. A better understanding of prognostic parameters helps in the selection of patients with a chance of benefiting from systemic immunochemotherapy. For patients with rapidly progressing tumors or sarcomatoid dedifferentiation, new effective chemotherapy regimens are available. New angiogenesis inhibitors such as sutent, avastin or sorafenib can potentially be effectively used in future therapeutic regimens.
Literatur
Flanigan RC, Campbell SC, Clark JI, Picken MM (2003) Metastatic renal cell carcinoma. Curr Treat Options Oncol 4: 385–390
Jemal A, Tiwari RC, Murray T et al. (2004) Cancer statistics, 2004. CA Cancer J Clin 54: 8–29
Kattan MW, Reuter V, Motzer RJ, Katz J, Russo P (2001) A postoperative prognostic nomogram for renal cell carcinoma. J Urol 166: 63–67
Motzer RJ, Mazumdar M (2004) Predicting survival of patients with metastatic renal cell carcinoma. Urologe A 43 [Suppl 3]: 135–136
Robson CJ, Churchill BM, Anderson W (1969) The results of radical nephrectomy for renal cell carcinoma. J Urol 101: 297–301
Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R (2001) Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet 358: 966–970
Flanigan RC, Salmon SE, Blumenstein BA et al. (2001) Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med 345: 1655–1659
Volkmer BG, Gschwend JE (2002) Value of metastases surgery in metastatic renal cell carcinoma. Urologe A 41: 225–230
Wiesner C, Jakse G, Rohde D (2002) Therapy of local recurrence of renal cell carcinoma. Oncol Rep 9: 189–192
Alves A, Adam R, Majno P, Delvart V, Azoulay D, Castaing D, Bismuth H (2003) Hepatic resection for metastatic renal tumors: is it worthwhile? Ann Surg Oncol 10: 705–710
Badalament RA, Gluck RW, Wong GY et al. (1990) Surgical treatment of brain metastases from renal cell carcinoma. Urology 36: 112–117
Blute ML, Leibovich BC, Cheville JC, Lohse CM, Zincke H (2004) A protocol for performing extended lymph node dissection using primary tumor pathological features for patients treated with radical nephrectomy for clear cell renal cell carcinoma. J Urol 172: 465–469
Pantuck AJ, Zisman A, Dorey F et al. (2003) Renal cell carcinoma with retroperitoneal lymph nodes: role of lymph node dissection. J Urol 169: 2076–2083
Durr HR, Maier M, Pfahler M, Baur A, Refior HJ (1999) Surgical treatment of osseous metastases in patients with renal cell carcinoma. Clin Orthop: 283–290
Piltz S, Meimarakis G, Wichmann M, Oberneder R, Jauch KW, Furst H (2003) Surgical treatment of pulmonary metastases from renal cancer. Urologe A 42: 1230–1237
Pfannschmidt J, Hoffmann H, Muley T, Krysa S, Trainer C, Dienemann H (2002) Prognostic factors for survival after pulmonary resection of metastatic renal cell carcinoma. Ann Thorac Surg 74: 1653–1657
Brinkmann OA, Bruns F, Prott FJ, Hertle L (1999) Possible synergy of radiotherapy and chemo-immunotherapy in metastatic renal cell carcinoma (RCC). Anticancer Res 19: 1583–1587
Andrews DW, Scott CB, Sperduto PW et al. (2004) Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 363: 1665–1672
Siebels M, Oberneder R, Buchner A et al. (2002) Ambulatory radiosurgery in cerebral metastatic renal cell carcinoma. 5-year outcome in 58 patients. Urologe A 41: 482–488
Wowra B, Siebels M, Muacevic A, Kreth FW, Mack A, Hofstetter A (2002) Repeated gamma knife surgery for multiple brain metastases from renal cell carcinoma. J Neurosurg 97: 785–793
Amato RJ (2000) Chemotherapy for renal cell carcinoma. Semin Oncol 27: 177–186
Pyrhonen SO (2004) Systemic therapy in metastatic renal cell carcinoma. Scand J Surg 93: 156–161
Rini BI, Vogelzang NJ, Dumas MC, Wade JL 3rd, Taber DA, Stadler WM (2000) Phase II trial of weekly intravenous gemcitabine with continuous infusion fluorouracil in patients with metastatic renal cell cancer. J Clin Oncol 18: 2419–2426
Nanus DM, Garino A, Milowsky MI, Larkin M, Dutcher JP (2004) Active chemotherapy for sarcomatoid and rapidly progressing renal cell carcinoma. Cancer 101: 1545–1551
Cotran RS, Pober JS, Gimbrone MA Jr et al. (1988) Endothelial activation during interleukin 2 immunotherapy. A possible mechanism for the vascular leak syndrome. J Immunol 140: 1883–1888
McDermott DF, Atkins MB (2004) Application of IL-2 and other cytokines in renal cancer. Expert Opin Biol Ther 4: 455–468
Negrier S, Escudier B, Gomez F et al. (2002) Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais d’Immunotherapie. Ann Oncol 13: 1460–1468
Decatris M, Santhanam S, O’Byrne K (2002) Potential of interferon-alpha in solid tumours: part 1. BioDrugs 16: 261–281
Fossa SD (2000) Interferon in metastatic renal cell carcinoma. Semin Oncol 27: 187–193
Marshall ME, Wolf M, Crawford ED, Thompson IM, Flanigan R, Balcerzak SP, Meyers FJ (1995) Evaluation of low dose alpha-interferon (Roferon-A) in patients with advanced renal cell carcinoma: a Southwest Oncology Group study. Cancer Biother 10: 205–209
Heinzer H, Huland E, Huland H (2002) Regional immunotherapy of metastatic renal cell carcinoma. Urologe A 41: 239–248
Huland E, Heinzer H, Huland H (1999) Treatment of pulmonary metastatic renal-cell carcinoma in 116 patients using inhaled interleukin-2 (IL-2). Anticancer Res 19: 2679–2683
Rohrmann K, Schleypen J, Adam C, Hofstetter A, Siebels M (2004) Complete remission of pulmonary metastasized renal cell carcinoma after inhalative Interleukin-2 therapy. Urologe A 43: 1271–1274
Pyrhonen S, Salminen E, Ruutu M et al. (1999) Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. J Clin Oncol 17: 2859–2867
Aass N, De Mulder PH, Mickisch GH et al. (2005) Randomized phase II/III trial of interferon Alfa-2a with and without 13-cis-retinoic acid in patients with progressive metastatic renal cell Carcinoma: the European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group (EORTC 30951). J Clin Oncol 23: 4172–4178
Atzpodien J, Kirchner H, Jonas U et al. (2004) Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). J Clin Oncol 22: 1188–1194
Escudier B, Chevreau C, Lasset C et al. (1999) Cytokines in metastatic renal cell carcinoma: is it useful to switch to interleukin-2 or interferon after failure of a first treatment? Groupe Francais d’Immunotherape. J Clin Oncol 17: 2039–2043
Negrier S (2004) Better survival with interleukin-2-based regimens? Possibly only in highly selected patients. J Clin Oncol 22: 1174–1176
Gnarra JR, Tory K, Weng Y, Schmidt L et al. (1994) Mutations of the VHL tumour suppressor gene in renal carcinoma. Nat Genet 7: 85–90
Turner KJ, Moore JW, Jones A et al. (2002) Expression of hypoxia-inducible factors in human renal cancer: relationship to angiogenesis and to the von Hippel-Lindau gene mutation. Cancer Res 62: 2957–2961
Ohh M, Park CW, Ivan M et al. (2000) Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nat Cell Biol 2: 423–427
Semenza GL (2002) HIF-1 and tumor progression: pathophysiology and therapeutics. Trends Mol Med 8: S62–67
Bleumer I, Knuth A, Oosterwijk E et al. (2004) A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients. Br J Cancer 90: 985–990
Hilger RA, Scheulen ME, Strumberg D (2002) The Ras-Raf-MEK-ERK pathway in the treatment of cancer. Onkologie 25: 511–518
Fukuoka M, Yano S, Giaccone G et al. (2003) Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. J Clin Oncol 21: 2237–2246
Rowinsky EK, Schwartz GH, Gollob JA et al. (2004) Safety, pharmacokinetics, and activity of ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with metastatic renal cell cancer. J Clin Oncol 22: 3003–3015
Motzer RJ, Rini BI, Michaelson MD, Redman BG, Hudes GR, Wilding G, Bukowski RM, George DJ, Kim ST, Baum C, Group aSS (2005) Sunitinib Malat (SU11248) shows antitumor activity in patients with metastatic renal cell carcinoma: actual phase-II results. ECCO Abstr. 797
Escudier B, Szczylik C, Eisen T et al. (2005) Randomized phase III trial of the multi-kinase inhibitor sorafenib (BAY 43–9006) in patients with advanced RCC. ECCO Abstr.
Atkins MB, Hidalgo M, Stadler WM et al. (2004) Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol 22: 909–918
Interessenkonflikt:
Es besteht kein Interessenkonflikt. Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen. Die Präsentation des Themas ist unabhängig und die Darstellung der Inhalte produktneutral.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Staehler, M., Haseke, N., Schöppler, G. et al. Therapiestrategien des fortgeschrittenen Nierenkarzinoms. Urologe 45, 99–112 (2006). https://doi.org/10.1007/s00120-005-0982-6
Issue Date:
DOI: https://doi.org/10.1007/s00120-005-0982-6