Fracture-related hospitalisations in newly diagnosed high-risk localised or metastatic hormone-sensitive prostate cancer: secondary analysis of the STAMPEDE phase 3 trials of docetaxel and zoledronic acid using healthcare systems data
Menée en Angleterre à partir de données portant sur 2 140 patients atteints d'un cancer de la prostate hormonosensible de stade localisé, à haut risque de récidive ou métastatique, cette étude analyse le risque d'hospitalisation pour une fracture osseuse en lien avec une utilisation d'acide zolédronique avec ou sans docétaxel
Background: Androgen deprivation therapy (ADT), the mainstay systemic treatment for high risk non-metastatic (M0) and metastatic (M1) prostate cancer (PCa) is associated with bone loss and increased fracture risk. The STAMPEDE trial tested the addition of zoledronic acid ± 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 pts recruited from England and randomised to standard-of-care (SOC) ADT compared with SOC plus zoledronic acid or docetaxel or both docetaxel and zoledronic acid. ICD10 diagnosis and OPCS procedure codes from inpatient hospital admissions were used to identify fracture-related hospitalisations (FRH). Flexible parametric competing risks models were used to estimate 5- and 10-year cumulative incidence and sub-distribution hazard ratios (SDHR).
Results: 2,140 of 2,705 (79%) pts recruited from trial sites in England were eligible for this secondary analysis. Linked data were available for 2,042/2,140 (96%) pts (734 M0, 1,308 M1). 5-year cumulative incidence of fracture for M0 and M1 pts treated with SOC only was 11% (95% CI, 8-15%) and 23% (95% CI, 19-28%) respectively. 10-year cumulative incidence in M0 pts was 26% (95% CI, 20-33%). Allocation to zoledronic acid significantly reduced the risk of fracture in M1 pts (SDHR 0.73, 95% CI 0.55-0.97; p=0.015) but not M0 pts (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) pts.
Conclusions: High cumulative incidence of fracture was observed in both non-metastatic and metastatic PCa patients receiving ADT. The addition of zoledronic acid to ADT ± docetaxel significantly reduced long-term fracture risk in metastatic participants but had no clear effect in non-metastatic disease. These data support the use of bone protective agents to reduce fracture risk in men with metastatic prostate cancer undergoing ADT.
Annals of Oncology , article en libre accès, 2025