The Outcome of Patients Treated with Sunitinib Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer

Abstract Background The role of cytoreductive nephrectomy in metastatic clear cell renal cell carcinoma (ccRCC) is controversial. Objective To determine the outcome of patients with metastatic ccRCC who receive sunitinib prior to planned nephrectomy. Design, setting, and participants The study combined the data from two prospective phase 2 studies that assessed upfront sunitinib (12–16 wk) prior to nephrectomy in previously untreated patients with metastatic renal cell carcinoma (RCC). Sunitinib was discontinued during the perioperative period (median: 29 d). Intervention Sunitinib 50 mg in six weekly cycles (4 wk on, 2 wk off). Measurements Progression-free (PFS) and overall survival (OS) using the Kaplan-Meier method. Results and limitations Twenty-one patients (32%) had Memorial Sloan-Kettering Cancer Centre (MSKCC) poor-risk disease; 45 (68%) had intermediate-risk disease. Nephrectomy was not performed in 19 (29%), most commonly due to disease progression ( n = 12). The PFS for the cohort was 6.3 mo (95% confidence interval [CI], 5.1–8.5). Seventeen (36%) patients progressed during the treatment break, 13 (76%) of whom stabilised upon reinitiating of sunitinib. The OS for the cohort was 15.2 mo (95% CI, 10.3–NA). The OS for the intermediate MSKCC risk group was significantly longer than that for the poor-risk group (26.0 mo [95% CI, 13.6–NA] and 9.0 mo [95% CI, 5.8–20.5], respectively; p < 0.01). In multivariate analysis, progression of disease prior to planned nephrectomy (hazard ratio [HR]: 5.34; 95% CI, 3.17–13.27), high Fuhrman grade (HR 3.27; 95% CI, 1.38–7.72), and MSKCC poor risk at diagnosis (HR 4.75; 95% CI, 2.05–11.02) were associated with short survival ( p < 0.01). However, in the absence of randomised studies it is not possible to determine if this approach is beneficial. Conclusions Upfront sunitinib prior to planned nephrectomy in intermediate-risk disease is associated with a median survival of >2 yr despite frequent progression during treatment break. Progression in metastatic sites prior to planned surgery and MSKCC poor-risk disease was associated with a poor outcome.