ASCO 2017: Microvessel density as a prognostic marker in high-risk renal cell carcinoma

Chicago, IL ( Increased vascularity is a known hallmark of renal cell carcinomas (RCC), particularly of the clear cell subtype. The vascular endothelial growth factor (VEGF) pathway implicated in tumor angiogenesis, is dysregulated in RCC. The phase 3 trial ECOG-ACRIN E2805 enrolled 1,943 patients with resected high-risk RCC (pT1b high grade to pT4 any grade or N any). In this trial patients were randomized to adjuvant sunitinib, sorafenib, or placebo. Dr. Weiss presented a study aiming to determine the prognostic and predictive role of micro-vessel density (MVD), VEGF receptors, and ligands in nephrectomy specimens from RCC patients at high risk of recurrence.

The authors obtained pre-treatment primary RCC tissue from 822 pts and built tissue microarrays using 3 cores from each sample. Using quantitative immunofluorescence they measured tumor MVD (area of CD34-expressing cells) and intensity of the VEGF/VEGF-R family (VEGF-R1, R2, R3 and VEGF-A, B, C, D) in tumor cells. The association with disease-free survival (DFS) and overall survival (OS) was assessed, and associations with the treatment arm and clinicopathologic variables were determined.

Of the 822 patients, 319 (38.8%) had disease recurrence. High MVD (above the median) was associated with prolonged OS for the entire cohort (p = 0.021, HR 0.63) and for pts treated in the placebo group (p = 0.014). The association between high MVD and OS was weaker in patients treated with sunitinib or sorafenib (p = 0.060). High VEGFD expression overall was associated with shorter OS (p = 0.027) but not for placebo (p = 0.16). Yet high MVD was not associated with improved DFS (p = 1.00). Univariate analysis showed that high MVD correlated with above-median age (> 56) (p = 0.032), Fuhrman grade I/II (p < 0.001), clear cell histology (p < 0.001), and absence of necrosis (p < 0.001) but not with gender, sarcomatoid features, lymphovascular invasion, or tumor size. In multivariable analysis, MVD remained independently associated with improved OS for the entire cohort (p = 0.013).

In conclusion, high MVD in nephrectomy specimens of high-risk RCC pts is associated with improved OS, regardless of treatment. MVD is thus an independent prognostic, rather than predictive, biomarker. Additional research should assess whether incorporating MVD into clinical models will predict outcome in resected high-risk RCC pts and if MVD can be used for patient selection for adjuvant therapy.

Presented By: Sarah A. Weiss, Yale School of Medicine, New Haven, CT

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre
Twitter: @GoldbergHanan

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA

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