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Changes of Biochemical Markers of Bone Turnover and YKL-40 Following Hormonal Treatment for Metastatic Prostate Cancer Are Related to Survival

Authors' Affiliations: Departments of ¹ Rheumatology, Herlev Hospital, ² Urology and ³ Finsen Laboratory, Rigshospitalet, ⁴ Surgical Gastroenterology, Hvidovre Hospital, University of Copenhagen, and ⁵ Research Centre for Prevention and Health, Copenhagen, Denmark, ⁶ Department of Immunology and Microbiology, University of Odense, Odense, Denmark, ⁷ Institut National de la Sante et de la Recherche Medicale Research Unit 664 and Molecular Markers, Synarc, Lyon, France; and ⁸ Department of Biology, University of California San Diego, La Jolla, California

Requests for reprints: Julia S. Johansen, Department of Rheumatology Q107, Herlev Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark. Phone: 45-44884243; Fax: 45-44884214; E-mail: julia.johansen{at}post3.tele.dk.

Purpose: Elevated serum levels of biochemical markers of bone turnover and YKL-40 in patients with metastatic prostate cancer (PC) at the time of diagnosis are associated to poor prognosis. In this study, we evaluated the value of these biomarkers in monitoring the patients during hormonal treatment.

Experimental Design: Serum procollagen type I N-terminal propeptide (PINP), bone-specific alkaline phosphatase (BAP), CTX-I, and YKL-40 were determined by ELISA in a longitudinal study of 106 patients with metastatic PC during treatment with total androgen ablation or parenteral estrogen. Serum samples were collected with 3 months interval. Median observation time was 4.9 years (range, 3.6-6.2). A total of 78 patients died (64 within 7 months following the last blood sampling).

Results: After 6 months treatment, serum PINP, BAP, and YKL-40 decreased (P < 0.0001), but not serum CTX-I compared with baseline values. Univariate Cox analysis showed that serum PINP at 6 months [log transformed and treated as a continuous variable; hazard ratio (HR), 2.2; P < 0.0001], serum BAP (HR, 1.8; P < 0.0001), and serum CTX-I (HR, 2.4; P < 0.0001), but not serum YKL-40 (HR, 1.4; P = 0.16) were associated with survival. Multivariate Cox analysis including the biomarkers 6 months after the start of treatment showed that Soloway score (HR, 3.9; P = 0.013), WHO tumor grade (HR, 3.9; P = 0.004), and serum PINP (HR, 2.2; P < 0.0001) were independent prognostic variables of survival. Scoring the biomarkers during treatment as time-dependent covariates in univariate Cox regression analysis showed that increases in serum PINP (HR, 2.0; P < 0.0001), BAP (HR, 2.1; P < 0.0001), and YKL-40 (HR, 2.1; P < 0.0001) were predictors of early death.

Conclusions: Serial monitoring of serum PINP, BAP, CTX-I, and YKL-40 in metastatic PC patients during hormonal treatment provided information of prognosis.