Rini B.I., Plimack E.R., Takagi T., Elson P., Wood L.S., Dreicer R., Gilligan T., Garcia J., Zhang Z., Kaouk J., Krishnamurthi V., Stephenson A.J., Fergany A., Klein E.A., Uzzo R.G., Chen D.Y.T., Campbell S.C.
Journal of Urology 2015
Purpose: Preservation of renal function is prioritized during surgical management of localized renal cell carcinoma. VEGF targeted agents can downsize tumors in metastatic renal cell carcinoma and may do the same in localized renal cell carcinoma, allowing for optimal preservation of renal parenchyma associated with partial nephrectomy. Materials and Methods: Localized clear cell renal cell carcinoma patients meeting 1 or both of the following criteria were enrolled in a prospective phase II trial, including radical or partial nephrectomy likely to yield a glomerular filtration rate of less than 30 ml/minute/1.73 m<sup>2</sup>, or partial nephrectomy high risk due to high complexity (R.E.N.A.L. 10 to 12) or tumor adjacent to hilar vessels. Pazopanib (800 mg once daily) was administered for 8 to 16 weeks with repeat imaging at completion of therapy, followed by surgery. Results: A total of 25 patients enrolled with a median tumor size of 7.3 cm and amedian R.E.N.A.L. score of 11. Of index lesions 80% were high complexity and 56% of patients had a solitary kidney. Patients received a median of 8 weeks of pazopanib. The median interval from treatment start to surgery was 10.6 weeks. R.E.N.A.L. score decreased in 71% of tumors and 92% of patients experienced areduction in tumor volume. Six of 13 patients for whom partial nephrectomy was not possible at baseline were able to undergo partial nephrectomy after treatment. The mean parenchymal volume that could be saved with surgery increased from an estimated 107 to 173 cc (p = 0.0015). In 5 patients a urine leak developed, which was managed conservatively, and 7 received a transfusion, of whom 1 required embolization. Conclusions: Neoadjuvant pazopanib resulted in downsizing localized renal cell carcinoma, allowing for improved preservation of renal parenchyma and enabling partial nephrectomy in a select subset of patients who would otherwise require radical nephrectomy.