Background: Carmena was a randomized phase III trial, testing the benefit of CN followed by sunitinib (arm A) vs sunitinib alone (arm B), with stratification by MSKCC risk groups in 450 mRCC patients. Based on this trial, CN is not anymore recommended in mRCC (NEJM, Mejean et al, 2018). However there are questions about which patients could still benefit from CN, especially in intermediate risk group. In the present study, we investigated different subgroups from the Carmena trial to answer these questions. Methods: Carmena trial was initially stratified according to MSKCC risk groups. For the purpose of this analysis, we reclassified the patients based on IMDC risk groups. We also analyzed patients with one metastatic site vs more than one, as well as patients with secondary nephrectomy in arm B. Overall survival (OS) was the primary endpoint. Results: With a updated median FU of 61.5 months (mo), the median OS by ITT analysis was 15.6 vs 19.8 mo in arm A and B respectively stratified on MSKCC (HR 0.933 ; 95% CI [0.76- 1.15]) / stratified on IMDC (HR 0.957 ; 95% CI [0.78- 1.18]). Using IMDC risk group factors, 58.6% patients were intermediate and 41.4 % were poor risk. When looking at intermediate risk group only, 48.1% had only one risk factor (interval between diagnosis and treatment < 1y), with a median OS of 30.5 and 25.2 mo in arm A and B respectively (HR 1.24 [0.81 – 1.90]). By contrast, 51.9 % had two risk factors (mostly low hemoglobin, high corrected calcium or neutrophils), with a median OS of 16.6 and 31.2 mo in arm A and B respectively (HR 0.61 [0.41 – 0.91] p = 0.015). Regarding number of metastatic sites, 33% had only one metastatic site. Median OS was 23.6 and 22.7 mo in arm A and B respectively (HR 1.08 [0.75 – 1.57]. Finally, 40 patients had a secondary nephrectomy in arm B, with median OS of 48.5 mo [CI 95%: 27.9-64.4] vs 15.7 mo [CI 95%: 13.3-20.5] in patients who never had surgery. Conclusions: With longer FU, Carmena trial confirms that CN is not superior to sunitinib alone in ITT population, both with MSKCC and IMDC risk groups. However for patients with only one IMDC risk factor, CN might be beneficial. Number of metastatic site is not helpful to define good candidates for surgery. Finally, patients with secondary nephrectomy have very long OS, supporting this strategy. Clinical trial information: NCT00930033