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 50mg 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. [Copyright &y& Elsevier]