Predictive implications of bone turnover markers after palliative treatment with (186)Re-HEDP in hormone-refractory prostate cancer patients with painful osseous metastases.

Abstract

To prospectively evaluate the predictive value of various bone formation and resorption markers in patients with bone metastases from prostate cancer after palliative treatment with (186)Re-1,1-hydroxyethylidene diphosphonate ((186)Re-HEDP). Included in the study were 36 men with prostate cancer, suffering from painful osseous metastases and treated with (186)Re-HEDP. None had received any treatment that would have interfered with bone metabolism before (186)Re-HEDP treatment or throughout the follow-up period. For each patient, pretreatment and posttreatment serum levels of osteocalcin (OC), bone alkaline phosphatase (BALP), aminoterminal (PINP) and carboxyterminal (PICP) propeptides of type I collagen, amino-terminal (NTx) and carboxyterminal (CTx) telopeptides of type I collagen and their combinations were compared with the level and duration of pain response to radionuclide treatment. Pain response was correlated only with pretreatment NuTaux/PINP, PICP/PINP and NTx/CTx ratios and posttreatment decrease in baseline NTx and PICP values (p = 0.0025-0.035). According to multivariate and ROC analyses, the best marker-derived predictors of better and longer duration of response to (186)Re-HEDP treatment were a posttreatment decrease in NTx of > or = 20% (RR = 3.44, p = 0.0005) and a pretreatment NTx/PINP ratio of > or = 1.2 (RR = 3.04, p = 0.036) NTx, a potent collagenous marker of bone resorption, along with the novel NTx/PINP ratio provide useful cut-off values for identifying a group of patients suffering from painful osseous metastases from hormone-refractory prostatic carcinoma who do not respond to palliative treatment with (186)Re-HEDP. This information could help avoid an inefficient and expensive radionuclide treatment. Also, in the cohort of patients who will eventually undergo such treatment, the medium-term posttreatment changes in NTx offer valuable predictive information regarding long-term palliative response.