Failure to suppress markers of bone turnover on first-line hormone therapy for metastatic prostate cancer is associated with shorter time to skeletal-related event

Abstract

Background: Elevated markers of bone turnover are prognostic for shorter survival in castration-resistant prostate cancer. We aimed to determine the prognostic value of bone turnover markers in metastatic hormone-sensitive prostate cancer.

Patients and methods: Markers of bone turnover (urine deoxypyridinoline [DPD] and N-telopeptide, serum bone alkaline phosphatase (AP), and osteocalcin [OC]) from baseline and after 6 months of study were assessed in men enrolled in a prospective metastatic prostate cancer trial with androgen deprivation therapy (ADT) with or without risedronate (ClinicalTrials.gov, NCT00216060).

Results: Serum samples were collected from 63 patients with bone involvement and a median follow-up of 39.7 months. A multivariate model using Cox regression-which included prostate-specific antigen (PSA) nadir, bisphosphonate treatment, and extent of metastases-showed that suppression of bone turnover markers after 6 months of therapy compared with baseline was significantly associated with longer skeletal-related event (SRE)-free survival. ADT without bisphosphonate therapy was also associated with a decline in markers of bone turnover, presumably resulting from direct anticancer activity. Elevated baseline bone turnover markers were not prognostic.

Conclusion: Failure to suppress bone turnover while receiving ADT, even when otherwise responding to therapy, may identify patients with hormone-sensitive metastatic prostate cancer who are destined for a shorter time to SREs and progression.

Keywords: Androgen deprivation therapy; Bone turnover; Prostate cancer; Skeletal-related events.