Increases in bone turnover marker levels at an early phase after starting zoledronic acid predicts skeletal‐related events in patients with prostate cancer with bone metastasis

• Published in: BJU international Vol. 109; no. 3; pp. 394 - 400
• Main Authors: Izumi, Kouji, Mizokami, Atsushi, Itai, Shingo, Shima, Takashi, Shigehara, Kazuyoshi, Miwa, Sotaro, Maeda, Yuji, Konaka, Hiroyuki, Koh, Eitetsu, Namiki, Mikio
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2012; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: Aged; Aged, 80 and over; Alkaline phosphatase; Alkaline Phosphatase - metabolism; Biological and medical sciences; biomarkers; Biomarkers - metabolism; Bone cancer; Bone Density Conservation Agents - administration & dosage; bone metastasis; Bone Neoplasms - drug therapy; Bone Neoplasms - secondary; Bone Remodeling - drug effects; Bone turnover; bone turnover marker; Collagen; Collagen Type I - metabolism; Diphosphonates - administration & dosage; Drug Administration Schedule; Gynecology. Andrology. Obstetrics; Humans; Imidazoles - administration & dosage; Kaplan-Meier Estimate; Male; Male genital diseases; Medical sciences; Metastases; Middle Aged; Nephrology. Urinary tract diseases; Peptide Fragments - metabolism; Peptides - metabolism; Procollagen - metabolism; Prognosis; Prostate cancer; prostate-specific antigen; Prostatic Neoplasms; Retrospective Studies; skeletal‐related events; Survival; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Zoledronic acid; Nephrology; Antiosteoporotic; Prostate disease; Prostate metastasis; Diseases of the osteoarticular system; Antiresorptive agent; Biological marker; Diphosphonic acid derivatives; Bisphosphonates; Urology; Osteoarticular system; skeletal-related events; Antiosteoclastic agent; bone turnover marker; Turnover; Zoledronic acid; Skeleton; Male genital diseases; Human; Urinary system disease; Early phase; Biological indicator; Malignant tumor; Bone metastasis; Bone cancer; Bone; Predictive factor; Prostate cancer; Cancer
• ISSN: 1464-4096; 1464-410X; 1464-410X
• DOI: 10.1111/j.1464-410X.2011.10192.x

Study Type – Prognosis (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Bone turnover markers such as BAP and 1CTP in patients with SRE or metastatic bone progression were significantly higher at a later phase after starting treatment with zoledronic acid compared with those without SRE or progression. However, there are no evident biomarkers predicting SRE or survival at an early phase after starting zoledronic acid treatment. The increase in serum 1CTP and BAP levels at an early phase after starting zoledronic acid treatment predicts short SRE‐free survival and overall survival. The measurement of bone turnover markers may be useful for physicians to inform patients of their prognosis and to determine the subsequent treatment plan. OBJECTIVE • To examine whether bone turnover markers could be predictive markers of the probability of newly arising skeletal‐related events (SRE) after the start of zoledronic acid treatment in patients with prostate cancer with bone metastasis. PATIENTS AND METHODS • In all, 30 patients with prostate cancer with bone metastasis were treated with zoledronic acid infusion every 4 weeks. • Serum C‐terminal crosslinking telopeptide of type 1 collagen (1CTP), bone alkaline phosphatase (BAP), and prostate‐specific antigen (PSA) levels were measured at the start of zoledronic acid treatment to establish baseline values, and every 4 weeks thereafter. • To judge in the early phase whether zoledronic acid is effective in these patients, we retrospectively compared 1CTP, BAP, and PSA levels at 1, 3, and 6 months after starting zoledronic acid treatment with those at baseline. RESULTS • SRE‐free survival of patients with increases of 1CTP levels at 1 and 3 months and BAP levels at 3 months were significantly poorer than those of patients with decreases in 1CTP or BAP levels (P = 0.001, P = 0.042, and P = 0.004, respectively). • Overall survival of patients with increases of 1CTP levels at 1 and 3 months and of BAP levels at 6 months were significantly poorer than those of patients with decreases of 1CTP or BAP levels (P = 0.013, P = 0.027, and P = 0.035, respectively). CONCLUSION • The measurement of 1CTP and BAP levels at an early phase after starting zoledronic acid treatment may be useful for physicians to inform patients of their prognosis and to determine the subsequent treatment plan.