Author Reply

Abstract

We are pleased that the editorial acknowledges that a select population of patients with primary low-volume metastatic renal cell carcinoma (mRCC) that cannot be completely resected may benefit from a period of observation after cytoreductive nephrectomy (CN) before further progression requires medication. Synchronous mRCC is considered to have a more aggressive behavior than metachronous metastatic disease that develops with a latency after nephrectomy in patients with previously nonmetastatic RCC. Nevertheless, multiple studies as well as clinical prognostic risk models suggest that synchronous mRCC represents a heterogenous disease spectrum with a broad range of survival. 1 Heng D.Y. 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 Abstract Full Text Full Text PDF PubMed Scopus (325) Google Scholar Some patients with solitary or oligometastasis can be induced into long-term remission by complete resection of disease, whereas others, particularly those with multiple metastatic sites and poor performance status, have a short overall survival (OS) and poor outcome regardless of surgery or systemic therapy. 2 Bex A. Ljungberg B. van Poppel H. Powles T. The role of cytoreductive nephrectomy: European Association of Urology recommendations in 2016. Eur Urol. 2016; 70: 901-905 Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar Large retrospective studies consistently demonstrate a survival benefit after CN but are likely confounded by unconsidered characteristics that may be associated with treatment choices or outcome, such as metastatic burden, subtype, grade, performance, age, and comorbidities. 1 Heng D.Y. 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 Abstract Full Text Full Text PDF PubMed Scopus (325) Google Scholar , 3 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 Crossref PubMed Scopus (157) Google Scholar For example, we demonstrated previously in a propensity-score–matched analysis from a population-based registry that CN may be effective in patients receiving sunitinib, but that the benefit was modest when correcting for time from diagnosis to sunitinib treatment. 4 de Groot S. Redekop W.K. 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: 121-127 Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Patients with synchronous mRCC with a time of 1 year or longer to systemic therapy had a better OS than patients who started sunitinib within a year after diagnosis. Similarly, patients in our observation study had a median time to targeted therapy of more than 1 year and a long median OS. Two randomized controlled trials, CARMENA (NCT00930033) and SURTIME (NCT01099423), are investigating the role and sequence of CN in the era of vascular endothelial growth factor receptor-targeted therapy. 2 Bex A. Ljungberg B. van Poppel H. Powles T. The role of cytoreductive nephrectomy: European Association of Urology recommendations in 2016. Eur Urol. 2016; 70: 901-905 Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar It should be pointed out that patients who were part of our retrospective observation study would probably not have been eligible for both the CARMENA and SURTIME studies, which required participants to have an immediate need for systemic therapy. When these studies report, the results are unlikely to represent outcome for the particular group of patients described in our study. It is therefore important that data on observation of metastases including additional local therapies for limited progression after CN are available to aid the clinical decision when to start systemic therapy.