AIMS: To assess the strategy of using an absence of progression at metastatic sites following initial cytokine therapy outcome as a selection criterion for nephrectomy in patients with synchronous metastatic renal carcinoma and an intermediate prognosis according to the Memorial Sloan Kettering prognostic index classification. MATERIALS AND METHODS: A combined retrospective analysis of patients with clear-cell subtype from studies of initial cytokine treatment response to assist with selection of patients for nephrectomy. We analyzed survival times, UCLA integrated staging system scores, number of nephrectomies and risk of progression to unresectability of the primary tumor during treatment. RESULTS: There were 33 patients in total. Nephrectomies were not performed in 10 (30%) patients whose cancers had progressed at metastatic sites. Median survival time was 4 months with none of the patients dying of local tumor progression. The median survival time of the 21 patients with nonprogressive cancer and the primary removed was 17 months. Of those, 8 had a survival time < or =1 year (median 8.5 months) and a progression-free survival time of 4 months and 13 had a survival time >1 year (median 25 months). The median progression-free survival time was 7 months (4-57 months). Four of the 5 objective responses at metastatic sites (5/33, 14%) occurred in those surviving >1 year. CONCLUSIONS: We propose that progression at metastatic sites during initial immunotherapy may be used to identify patients with a short survival time and who are unlikely to benefit from nephrectomy. 2008 S. Karger AG, Basel.