1049 RANKL pathway proteins as risk parameters for biochemical recurrence in patients undergoing radical prostatectomy

Abstract

INTRODUCTION AND OBJECTIVES: The development of bone metastases from prostate cancer is closely linked to the activity of the receptor activator of the NF-kB Ligand (RANKL) pathway. Recent evidence exists that this pathway might play a role for tumor biology before metastatic disease becomes manifest. We aimed to assess the prognostic impact of proteins of the RANKL pathway in serum samples of patients undergoing radical prostatectomy (RP). METHODS: In total, 178 patients undergoing RP between 2004 and 2006 were included. Serum concentrations of soluble RANKL (sRANKL) and osteoprotegerin (OPG) were determined retrospectively using Enzyme Linked Immunosorbent Assay (ELISA). Results of serum measurements were correlated to clinical and patient follow-up data using the Wilcoxon-Mann-Whitney test, the Kaplan-Maier method, and single variable or multifactorial Cox proportional hazards analysis. RESULTS: Increased sRANKL (p 0.01), decreased OPG (p 0.01) and an increased sRANKL/OPG Ratio (p 0.004) were significant risk factors for biochemical recurrence (BCR). In multifactorial analysis adjusted for classical risk factors for BCR, sRANKL and sRANKL/OPG ratio were confirmed as independent prognostic factors even when considered as continuous variables. Neither sRANKL nor OPG showed a clear association with classical histopathologic factors such as pT, pN, PSA, Gleason score or R status. CONCLUSIONS: Increased activity of the RANKL pathway in the serum of patients with prostate cancer undergoing RP is a risk factor for biochemical recurrence. The RANKL pathway seems to contribute to the biological behavior of prostate cancer already in an organ-confined stage of the disease. Whether serum proteins of this pathway are also able to predict response to RANKL-inhibition in patients without bone metastases remains to be elucidated.