Impact of androgen suppression and zoledronic acid on bone mineral density and fractures in the Trans-Tasman Radiation Oncology Group (TROG) 03.04 Randomised Androgen Deprivation and Radiotherapy (RADAR) randomized controlled trial for locally advanced prostate cancer

Authors


Abstract

Objective

  • To study the influence of adjuvant androgen suppression and bisphosphonates on incident vertebral and non-spinal fracture rates and bone mineral density (BMD) in men with locally advanced prostate cancer.

Patients and Methods

  • Between 2003 and 2007, 1071 men with locally advanced prostate cancer were randomly allocated, using a 2 × 2 trial design, to 6 months i.m. leuprorelin (androgen suppression [AS]) before radiotherapy alone ± 12 months additional leuprorelin ± 18 months zoledronic acid (ZdA), commencing at randomization.
  • The main endpoint was incident thoraco-lumbar vertebral fractures, which were assessed radiographically at randomization and at 3 years, then reassessed by centralized review.
  • Subsidiary endpoints included incident non-spinal fractures, which were documented throughout follow-up, and BMD, which was measured in 222 subjects at baseline, 2 years and 4 years.

Results

  • Incident vertebral fractures at 3 years were observed in 132 subjects. Their occurrence was not increased by 18 months’ AS, nor reduced by ZdA.
  • Incident non-spinal fractures occurred in 72 subjects and were significantly related to AS duration but not to ZdA.
  • Osteopenia and osteoporosis prevalence rates at baseline were 23.4 and 1.4%, respectively, at the hip.
  • Treatment for 6 and 18 months with AS caused significant reductions in hip BMD at 2 and 4 years (P < 0.01) and ZdA prevented these losses at both time points.

Conclusion

  • In an AS-naïve population, 18 months of ZdA treatment prevented the sustained BMD losses caused by 18 months of AS treatment; however, the study power was insufficient to show that AS duration or ZdA influenced vertebral fracture rates.

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