ABSTRACT
PURPOSE: 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). METHODS: 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. RESULTS: 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) CONCLUSION: 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.