Variations in serum P1NP, BAP and YKL-40 levels after start of treatment for advanced prostate cancer and the relation to prognosis

Abstract

4734 Background: The amino-terminal propeptide of type I procollagen (PINP) and bone alkaline phosphatase (BAP) are secreted by osteoblasts and are markers of bone formation. YKL-40 is a growth factor secreted by cancer cells and inflammatory cells. Increased serum PINP, BAP and YKL-40 levels are found in patients with advanced prostate cancer.The aim was to examine the variation of serum PINP, BAP and YKL-40 levels after start of treatment for advanced prostate carcinoma and the relation to prognosis. Methods: BAP, PINP and YKL-40 were determined by ELISA in serum samples obtained from 106 patients with advanced prostate carcinoma before and after start of treatment with total androgen ablation or parenteral estrogen. The median observation time was 5.0 years (range 3.6–6.2). 78 patients died. Results: At baseline all 3 biomarkers were significantly elevated (p<0.001) compared to controls. After 6 months of treatment the biomarkers were significantly (p<0.0001) decreased compared to baseline values (Serum P1NP: pre-treatment median (range) 156 μg/l (32–3112) vs. 6 months post-treatment 114 μg/l (31–1490); serum BAP: 51 U/l (9–2420) vs. 28 U/l (10–740); serum YKL-40: 133 μg/l (22–975) vs. 84 μg/l (20–484)). If serum PINP, BAP and YKL-40 levels at 6 months were log transformed and treated as continuous variables univariate Cox analysis showed that serum PINP (HR=1.9, 95% CI: 1.5–2.5, p<0.0001) and serum BAP (HR=1.8, 95% CI: 1.4–2.3, p<0.0001) but not serum YKL-40 (HR=1.3, 95% CI: 0.9–1.9, p=0.22) were significantly associated with survival. Multivariate Cox analysis including age, performance status, tumor stage, Soloway score, WHO tumor grade, and serum PINP, BAP and YKL-40 6 mths after start of treatment showed that Soloway score (HR=3.4, 95% CI: 1.8–6.6, p=0.0003), serum PINP (HR=1.6, 95% CI: 1.2–2.2, p=0.0017) and WHO tumor grade (HR=2.7, 95% CI: 1.3–5.6, p=0.0097) were independent prognostic variables of survival. Conclusions: High serum PINP or BAP levels 6 months after start of treatment with total androgen ablation or parenteral estrogen in patients with advanced prostate carcinoma are associated with poor prognosis. No significant financial relationships to disclose.