Predictive and Prognostic Clinicopathologic Factors of Metastatic Renal Cell Carcinoma Treated with VEGF-Targeted Therapy
Ji Young Park, Jae-Lyun Lee, Jae Y Ro, Yong Mee Cho. University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; Methodist Hospital, Cornell University, Houston, TX
Background: The targeted therapy against vascular endothelial growth factor (VEGF) signaling is the first-line treatment modality of metastatic renal cell carcinoma (mRCC). However, predictive factors of targeted therapy response and prognostic factors of mRCC treated with the VEGF-targed therapy remain to be defined.
Design: We retrospectively analyzed clinicopathologic features of 194 mRCC cases treated with the first-line VEGF inhibitors. Pathologic evaluation was made on the last RCC specimens harvested before the therapy. The specimens consisted of 122 nephrectomy specimens and 72 needle biopsy specimens of primary or metastatic tumors.
Results: Three cases (1.5%) achieved complete response and 64 cases (33.0%) had partial response. Eighty-eight cases (45.4%) were stated stable and 39 cases (20.1%) were progressed. Compared to complete and partial response cases, high Fuhrman nuclear grade (3 and 4) and tumor necrosis and sarcomatoid transformation each involving more than 10% of the tumor were frequently noted in stable and progressed cases (p<0.0001, p=0.006, and p<0.0001, respectively). The pathologic T stage, RCC subtype, sarcomatoid subtype, and tumor-associated inflammation were not correlated with the targeted therapy response. On univariate analysis, tumor necrosis and sarcomatoid transformation involving more than 10% of the tumor, high Fuhrman nuclear grade, lymphovascular invasion and multiple metastases involving more than 2 organs were associated with cancer-specific death (p<0.0001, p<0.001, p=0.015, p=0.0001, and p<0.001, respectively). Among these factors, tumor necrosis and multiple metastases remained as independent factors on multivariate analysis (p<0.002 and p<0.001, respectively).
Conclusions: This study suggests high Fuhrman nuclear grades, tumor necrosis, and sarcomatous transformation as prognostic and predictive factors in mRCC cases treated with the targeted therapy. Therefore, these pathologic features should be considered for the targeted treatment assessment in evaluation of mRCC patients.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 149, Monday Morning