Vascular endothelial growth factor and basic fibroblast growth factor urine levels as predictors of outcome in hormone-refractory prostate cancer patients: A cancer and leukemia group B study

Better prognostic markers are needed for hormone-refractory prostate cancer (HRPC) patients. No single biochemical or clinical parameter ran reliably predict patient response to therapy or rapidity of disease progression. Pep tide factors involved in major cancer growth pathways, such as tumor angiog enesis, are attractive candidates as markers of low- and high-risk HRPC pat ients. We analyzed prospectively collected urine specimens from 100 of 390 HRPC patients undergoing therapy with the growth factor antagonist suramin as part of CALGB 9480. Levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were assessed from day 1 of thera py (D1) and day 29 (D29) urine samples from this subset of 100 randomly sel ected patients. Growth factor levels were determined by standardized ELISA microtiter plate assays from a commercial (bFGF) or proprietary (VEGF) sour ce. Pretreatment urine VEGF levels were predictive of survival. In univaria te analysis, patients whose baseline urine VEGF level was less than or equa l to 28 pg/ml (the median level) had an average survival of 17 months; thos e with baseline VEGF >28 pg/ml had a significantly shorter survival of 10 m onths (P = 0.024). This difference corresponded to a 60% increased risk of dying for the higher urine VEGF patients (hazard ratio, 1.62; P = 0.03) and remained significant in multivariate analysis (hazard ratio, 1.72, P = 0.0 2). No significant correlations between urine bFGF level or change in bFGF levels and survival were found. These results support the notion that certa in peptide growth factor-mediated, mitogenic pathways are important in HRPC and that their levels can predict outcome.