European Urology

2. Discussion

Non–clear cell renal cell carcinoma represents 25% of all metastatic RCCs [2] x A.J. Schrader, P.J. Olbert, A. Hegele, Z. Varga, R. Hofmann. Metastatic non-clear cell renal cell carcinoma: current therapeutic options. BJU Int. 2008;101:1343-1345 Crossref. . Few data specifically address the possible therapeutic options for these tumors. Immunotherapy and chemotherapy have not proven any benefits for patients with such disease [3] x J.S. Lam, A. Breda, A.S. Belldegrun, R.A. Figlin. Evolving principles of surgical management and prognostic factors for outcome in renal cell carcinoma. J Clin Oncol. 2006;24:5565-5575 Crossref. . Targeted therapies with tyrosine kinase and mammalian target of rapamycin inhibitors have been limited historically to the clear cell RCC histology [4] x T.K. Choueiri, A. Plantade, P. Elson, et al. Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. J Clin Oncol. 2008;26:127-131 Crossref. . Despite this, temsirolimus has been recently shown to be beneficial in terms of overall survival for those patients with advanced metastatic RCC and multiple adverse prognostic factors independently of primary tumor histology 5 x G. Hudes, M. Carducci, P. Tomczak, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356:2271-2281 Crossref. , and 6 x J.P. Dutcher, P. de Souza, D. McDermott, et al. Effect of temsirolimus versus interferon-alpha on outcome of patients with advanced renal cell carcinoma of different tumor histologies. Med Oncol. 2009;26:202-209 Crossref. .

The historical role of cytoreductive nephrectomy in metastatic RCC 7 x Ljungberg B, Hanbury DC, Kuczyk MA, et al. Guidelines on renal cell carcinoma. European Association of Urology Web site. http://www.uroweb.org/fileadmin/tx_eauguidelines/2009/Full/RCC.pdf. Updated March 2009. , and 8 x R.C. Flanigan, G. Mickisch, R. Sylvester, et al. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol. 2004;171:1071-1076 Crossref. has also been argued since the advent of the new targeted therapies. A recent retrospective study evaluated the influence of prior nephrectomy versus no nephrectomy on overall and progression-free survival in metastatic patients treated with temsirolimus versus interferon. The study found that nephrectomy status did not affect temsirolimus efficacy with respect to either overall or progression-free survival. Therefore, the authors suggested that patients treated with temsirolimus may not need a cytoreductive nephrectomy [1] x T. Logan, D.F. McDermott, J.P. Dutcher, et al. Exploratory analysis of the influence of nephrectomy status on temsirolimus efficacy in patients with advanced renal cell carcinoma and poor risk features. J Clin Oncol. 2008;26:5050 .

Based on these findings, the European Association of Urology guidelines recommend temsirolimus as first-line treatment in high-risk patients with advanced metastatic RCC, regardless of tumor histology or nephrectomy status, to attempt to increase overall survival [7] x Ljungberg B, Hanbury DC, Kuczyk MA, et al. Guidelines on renal cell carcinoma. European Association of Urology Web site. http://www.uroweb.org/fileadmin/tx_eauguidelines/2009/Full/RCC.pdf. Updated March 2009. .

Given the fact that our patient had very poor prognostic factors, we decided to offer a neoadjuvant treatment with temsirolimus. After 6 wk of treatment, a CT scan was performed and showed a complete radiologic disappearance of the metastases and a significant downstaging of the tumor from stage T4 to T1b. Three months later, a laparoscopic radical nephrectomy with lymphadenectomy was performed. The surgery was uneventful, and no increased difficulties were encountered to suggest that the treatment with temsirolimus had not affected the surgical planes. The final staging was pT1bN0Mx, non–clear cell RCC with an eosinophilic component.

We believe these findings are important because they indicate that temsirolimus may offer not only some benefits in terms of overall survival but also a cytoreductive option in non–clear cell RCC that may therefore render a radical surgery possible. Furthermore, the role of a renal mass biopsy in metastatic RCC may be crucial in planning the therapeutic options. In our case, it was key to the final decision regarding a neoadjuvant treatment 9 x P. Nathan, J. Wagstaff, E. Porfiri, T. Powles, T. Eisen. UK guidelines for the systemic treatment of renal cell carcinoma. Br J Hosp Med (Lond). 2009;70:284-286 , and 10 x T.M. De Reijke, J. Bellmunt, H. van Poppel, S. Marreaud, M. Aapro. EORTC-GU group expert opinion on metastatic renal cell cancer. Eur J Cancer. 2009;45:765-773 Crossref. .

These findings have to be taken with all the limitations of a case report. However, we believe and hope that such a case may stimulate further investigations.