Use of Vegfr1 Expression in Benign Pelvic Lymph Nodes to Predict Biochemical Recurrence in Patients with High-Risk Prostate Cancer.

205 Background: High-risk prostate cancer (PCa) is a heterogeneous disease, and biomarkers that accurately predict clinical outcome within this subset are lacking. The pre-metastatic niche (PMN) represents one possible biomarker—this harbinger of future metastasis may be characterized by infiltration of VEGFR1+ cells [Kaplan et al Nature 139:820, 2005]. Given the predilection of PCa to spread to nodal sites, the association between VEGFR1 expression in benign pelvic lymph nodes and clinical outcome was examined. Methods: The City of Hope Prostate Cancer Registry (COH PCR) was used to identify 46 patients with high-risk PCa (baseline PSA > 20, pT3a-4 disease, or biopsy Gleason 8–10) who had undergone radical prostatectomy and pelvic lymph node dissection (PLND). The COH PCR prospectively collects clinical data associated with patients undergoing prostatectomy at the institution, and warehouses available clinical specimens. Benign tissue specimens derived from PLND were acquired for each patient, and were stained for VEGFR1 expression. VEGFR1+ cell clusters were counted within 8 distinct 40x fields, and the cluster count was averaged. Results: VEGFR1+ clustering in benign PLND specimens was a significant predictor of biochemical recurrence on multivariate Cox proportional hazards analysis, and outperformed other variables including established prognostic factors such as age, extracapsular spread, seminal vesicle invasion, and the aforementioned high-risk features. Patients with increased VEGFR1+ clustering pelvic lymph node tissue had a shorter interval to biochemical recurrence (HR 0.18, P<0.10). Conclusions: These preliminary results indicate that increased VEGFR1+ cell clustering in benign nodal tissue may predict poorer clinical outcome in patients with high-risk PCa. VEGFR1+ cells (a purported constituent of the PMN) represents a targetable entity. A randomized, phase II study employing axitinib (VEGFR1 IC50=1 nM) as neoadjuvant therapy in patients with high-risk PCa is nearing initiation at City of Hope ( NCT01385059 ).