Effect of Pelvic External Beam Radiation Therapy on Bone Mineral Density: A Secondary Analysis of a Phase III Randomized Controlled Trial

Purpose Pelvic radiotherapy may lead to decreased bone mineral density (BMD) and increased risk of fracture which could be of particular concern in prostate cancer (PCa) patients who also receive androgen deprivation therapy (ADT). We performed exploratory analysis of a randomized, double-blind, placebo-controlled trial to determine if exposure to prior pelvic external beam radiotherapy (XRT) affects BMD and risk of fracture in PCa patients treated with ADT. Methods Non-metastatic PCa patients with age ≥70 years or <70 years with low BMD (T-score < –1) or osteoporotic fracture, on ADT for ≥12 months, were randomly assigned to receive densoumab versus placebo every 6 months for 3 years. BMD was measured at baseline, and at months 1, 3, 6, 12, 24, and 36. We applied multivariable linear mixed effect models with an interaction term between the treatment arm and exposure to prior pelvic XRT to evaluate differential XRT effect on percent BMD change between the two treatment arms. Results Among 1407 eligible patients, 31% (n=447) of patients received prior pelvic radiotherapy. There was no difference in any clinical fractures among patients with (5.8%, 26 out of 447) or without (5.2%, 50 out of 960) prior pelvic radiotherapy (p=0.42). Receipt of prior pelvic XRT was associated with a significant 0.54 percent improvement in BMD (95% CI: 0.05 to 1.02) in the placebo group and a non-significant 0.04 percent decline in BMD (95% CI: –0.47 to 0.35) in the denosumab arm, respectively. (interaction p=0.007). There was no significant difference in pelvic radiotherapy effect on percent BMD change in lumbar spine (p=0.65) or total hip (p=0.39) between the two treatment groups. Conclusion We did not find sufficient evidence to suggest any detrimental impact of pelvic XRT on the treatment effect from denosumab on percent BMD change with only about 5% incidence of clinical fractures.