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

Thomas Powles, Christian Blank, Simon Chowdhury, Simon Horenblas, John Peters, Jonathan Shamash, Naveed Sarwar, Ekaterini Boleti, Anju Sahdev, Tim O'Brien, Dan Berney, Luis Beltran, Paul Nathan, John Haanen, Axel Bex*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    103 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)448-454
    Number of pages7
    JournalEuropean Urology
    Volume60
    Issue number3
    DOIs
    Publication statusPublished - Sept 2011

    Keywords

    • Sunitinib
    • Nephrectomy
    • Metastatic renal cancer
    • FDG-PET
    • INTERFERON-ALPHA
    • TARGETED THERAPIES
    • CARCINOMA
    • TRIAL
    • SURVIVAL
    • EFFICACY
    • ANGIOGENESIS
    • SAFETY

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