Serial Markers Of Bone Turnover In Men With Metastatic Prostate Cancer Treated With Zoledronic Acid For Detection Of Bone Metastases Progression

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Men's health
Article Date: 07 May 2007 - 0:00 PDT

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UroToday.com- Presently, bone imaging to include bone scans is used to determine the progression of prostate cancer (CaP) metastatic to bone. In patients with bone involvement, zoledronic acid (ZA) is shown to reduce skeletal related events. A report in the online version of European Urology by Dr. Lein and colleagues in Germany evaluates serial serum bone turnover markers in men treated with ZA to detect disease progression.

The markers studied were bone formation markers total alkaline phosphastase (tALP), bone-specific alkaline phosphatase (bALP), and amino-terminal procollagen propeptides of type I collagen (PINP). Also bone resorption markers cross-linked N-terminal (NTx) and cross-linked C-terminal (CTx) telopeptides of type I collagen and C-terminal telopeptides of type I collagen (ICTP). Patients included in the analysis were treated with ZA between 2002 and 2005. These 77 men were also treated with other standard CaP therapies to include androgen deprivation therapy, chemotherapy, corticosteroids and radiotherapy to treat non-skeletal and skeletal sites. Blood sampling was obtained prior to treatment with ZA and every 12 weeks thereafter. Metastatic bone progression was determined in 50 patients and non-progression was determined in 27 patients by lack of symptoms and bone scan progression at week 60. Almost all patients were receiving ADT before study entry and 31 men continued ADT during the study. Twenty-one men in the progression group and 4 in the non-progression group underwent chemotherapy during the study.

Five of 6 bone markers (tALP, bALP, PINP, NTx, CTx) decreased after beginning treatment with ZA. This was noted in both groups. In addition to the PSA changes, bone markers were significantly different between patients with and without bone progression. At weeks 24, 36, 48 and 60 after the beginning of ZA, patients with metastatic bone progression showed significantly higher levels of bone markers in addition to PSA. The authors used the 12 week decline in markers after the initiation of ZA as a baseline value and compared the increase from baseline as a significant indicator of disease progression. Patients with disease progression showed a significantly higher proportion with increased values compared with the baselines for all markers except for CTx, than the patients without progression. Bone formation markers (PINP, tALP, and bALP) generally showed better discrimination ability than bone resorption markers. The authors conclude that following the initiation of ZA therapy, an increase in bone marker concentrations above a post-treatment baseline nadir is associated with CaP progression. The study was single-armed and of limited numbers of patients, thus requiring further validation.

Lein M, Wirth M, Miller K, Eickenberg HU, Weißbach L, Schmidt K, Haus U, Stephan C, Meissner S, Loening SA, Jung K

Eur Urol 2007; epub DOI: 10.1016/j.eururo.2007.02.033

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