Fracture-related hospitalisations in newly diagnosed high-risk localised or metastatic hormone-sensitive prostate cancer: secondary analysis of the STAMPEDE phase III trials of docetaxel and zoledronic acid using healthcare systems data

Background

Androgen deprivation therapy (ADT), the mainstay systemic treatment for high risk non-metastatic (M0) and metastatic (M1) prostate cancer is associated with bone loss and increased fracture risk. The STAMPEDE trial tested the addition of zoledronic acid (ZA) ± docetaxel (with prednisolone) to ADT. Both regimens may impact bone health. However, long-term fracture incidence remains uncertain.

Patients and methods

Health systems data were obtained for patients recruited from England and randomised to standard-of-care (SOC) ADT compared with SOC plus ZA or docetaxel or both docetaxel and ZA. ICD10 diagnosis and OPCS procedure codes from inpatient hospital admissions were used to identify fracture-related hospitalisations. Flexible parametric competing risks models were used to estimate 5- and 10-year cumulative incidence and sub-distribution hazard ratios (SDHR).

Results

2140 of 2705 (79%) patients recruited from trial sites in England were eligible for this secondary analysis. Linked data were available for 2042/2140 (96%) pts (734 M0, 1308 M1). 5-year cumulative incidence of fracture for M0 and M1 patients treated with SOC only was 11% [95% confidence interval (CI), 8% to 15%] and 23% (95% CI, 19% to 28%), respectively. 10-year cumulative incidence in M0 patients was 26% (95% CI, 20% to 33%). Allocation to ZA significantly reduced the risk of fracture in M1 patients (SDHR 0.73, 95% CI 0.55-0.97; P = 0.015) but not M0 patients (SDHR 0.88, 95% CI 0.59-1.32; P = 0.549). Docetaxel had no clear effect on the risk of fracture in M0 (P = 0.570) or M1 (P = 0.264) patients.

Conclusions

High cumulative incidence of fracture was observed in both M0 and M1 prostate cancer patients receiving ADT. The addition of ZA to ADT ± docetaxel significantly reduced long-term fracture risk in M1 participants but had no clear effect in M0 disease. These data support the use of bone protective agents to reduce fracture risk in men with M1 prostate cancer undergoing ADT.