Histology-Radiology Correlation in Metastatic Clear Cell Renal Cell Carcinoma Treated with Pre-Operative Sorafenib and Nephrectomy.
William Dubinski, Tae K Kim, Jennifer J Knox, Antonio Finelli, Andrew J Evans. University Health Network, Toronto, ON, Canada
Background: The role for pre-operative tyrosine kinase inhibitor (TKI) therapy prior to cytoreductive nephrectomy (CN) in patients presenting with metastatic clear cell renal cell carcinoma (mCCRCC) is under investigation. While reports on tumor response to TKI therapy, as assessed by dynamic contrast-enhanced ultrasound (DCE-US) and CT (DCE-CT) exist, the effects of TKI therapy on the histomorphology of CCRCC have not been described. We present these findings in patients presenting with mCCRCC.
Design: Patients at University Health Network presenting with mCCRCC were entered into a clinical trial comprising pre-operative Sorafenib followed by CN. After confirming a diagnosis of CCRCC by core needle biopsy, each patient received Sorafenib for 12 weeks followed by CN and resection of metastatic deposits. Fresh CN specimens were bivalved coronally and compared with DCE-US/CT findings pre- and post-TKI.
Results: Sixteen patients (mean 55 years, range 40-70) presenting with mCCRCC (mean primary tumor diameter 10.9cm, range 6.5-15.8) were enrolled. The full spectrum of Fuhrman grades (FG) was observed in the pre-treatment biopsies, including one case with rhabdoid features. Following TKI therapy, mean tumor diameter fell to 9.6cm by DCE-US/CT (range 5.4-14.7cm) (p=.005). In all patients, post-TKI DCE-US/CT showed a pattern of central necrosis (∼90% vs. ∼30% pre-treatment) with a peripheral rim of viable tumor. Extensive histologic sampling (mean # of sections 19.9, range 8-52) of the CN specimens showed excellent correlation with DCE-US/CT and confirmed the impression of extensive central necrosis and viable tumor localized to the periphery. The H&E morphology of the viable tumor in the CN specimens was essentially unchanged from that observed in the pre-treatment biopsies. In 15 patients, the FG of the viable CCRCC in the CN specimens agreed with the biopsy FG to within 1 point. One patient with a FG 1 at biopsy was found to have FG 1-2 tumor at CN with admixed foci of FG 4 with rhabdoid features. The morphology of all resected metastatic deposits (17 from 8 patients) matched that of their primary tumors.
Conclusions: This study provides histologic confirmation of the treatment response typically observed radiologically following TKI therapy. Based on a comparison with pre-TKI tumor morphology in needle core biopsies, viable post-TKI tumor (in both the CN specimens and metastatic deposits) showed no significant morphologic or FG changes which could be interpreted as “treatment effects” resulting from TKI therapy.
Category: Genitourinary (including renal tumors)
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 123, Wednesday Morning