Early Primary Tumor Size Reduction Is an Independent Predictor of Improved Overall Survival in Metastatic Renal Cell Carcinoma Patients Treated With Sunitinib

Abstract

BackgroundIn metastatic renal cell carcinoma (mRCC) patients treated with targeted agents and their primary tumor (PT) in situ, early PT decrease in size correlates with improved overall PT response, but the effect on overall survival (OS) is unknown. ObjectiveTo evaluate whether early PT size reduction is associated with improved OS in patients with mRCC undergoing treatment with sunitinib. Design, setting, and participantsWe reviewed the clinical and radiographic data of all mRCC patients seen at our institution between January 2004 and December 2009 without prior systemic treatment who received sunitinib with their PT in situ. MeasurementsTwo independent reviewers measured the diameter of the PT and metastatic disease at baseline and subsequent scans to assess response. Early minor response was defined as ≥10% decrease within 60 d of treatment initiation. Univariate and multivariate analyses were used to calculate a hazard ratio (HR) corresponding to the risk of death based on clinical and pathologic factors as well as PT response. Results and limitationsWe identified 75 consecutive patients with a median follow-up of 15 mo. All patients were intermediate or poor risk by common risk stratification systems. Median initial PT diameter was 9.7cm. Median maximum PT size reduction was −10.2% overall and −36.4% in patients who had early minor PT response.Median OS for patients without minor PT response, with minor PT response after 60 d, and with early minor PT response was 10.3, 16.5, and 30.2 mo, respectively. On multivariate analysis, early minor response was an independent predictor of improved OS (HR: 0.26; p=0.031). Other significant predictors included venous thrombus, multiple bone metastases, lactate dehydrogenase above the upper limit of normal, symptoms at presentation, and more than two metastatic sites. ConclusionsEarly minor PT response is associated with improved OS. Future studies should evaluate this prognostic factor to identify patients with prolonged OS.