Bone Mineral Density Changes in Patients with Prostate Cancer Treated with Androgen Deprivation Therapy and External Beam Radiation Therapy: Hip and Spine Comparison

Abstract

Use of androgen-deprivation therapy (ADT) in high risk prostate cancer (PrCa) improves disease outcomes but decreases bone mineral density (BMD). External beam radiation therapy (RT) has been implicated in bone loss and skeletal events in the hip/pelvis. Little is known about differential BMD changes in skeletal sites over time in men with PrCa treated with long term ADT (LT-ADT) and RT. We hypothesized that there would be a greater decrease in BMD in the hip (RT exposed) than spine (not RT exposed). A retrospective review of men with PrCa treated with LT-ADT and definitive RT was conducted to evaluate BMD changes in the hip and spine. Patients treated from 2004 to 2017 were included if they received >1yr of ADT, pelvic RT as a component of treatment, and had baseline and follow up dual-energy X-ray absorptiometry (DXA) scan(s). ADT included total androgen blockade pre/during RT followed by LHRH agonist alone. Longitudinal comparisons of BMD changes between femoral neck (FN), total hip (TH) and lumbar spine (SP) from start of ADT were performed. Bone loss on DXA was managed as clinically indicated by T-score criteria (normal, osteopenia, osteoporosis). BMD decreases of ≥0.03 g/cm2 and change in T-score criteria were considered significant. FN and TH were contoured on and dosimetry collected from RT plans. A T-test was used to compare changes between sites (with a significance level of p<0.05). The 50 patients included for analysis had a median age of 68 yrs (43-82); duration of ADT of 27.8 mos (14.6-51.3); and follow up of 4.6 yrs (1.7-14.7). Mean doses from RT plans were: right FN 21.9 Gy (9.7-40.3) and TH 20.6 Gy (11.3-34.4), left FN 21.8 Gy (1-34.4) and TH 21.6 Gy (12.6-60.1). DXA scans at yearly timepoints (+/-6mos) were reviewed: n=35 at 1 yr, n=25 at 2 yrs, and n=11 at 3 yrs. Mean BMD declines (g/cm2) at FN, TH, and SP were: -0.026 (2.9%), -0.015 (1.4%), and -0.029 (2.3%) at 1 yr; -0.026 (2.7%), -0.045 (4.2%), and -0.027 (2%) at 2 yrs; and -0.042 (4.1%), -0.047 (4.4%), and -0.096 (7.6%) at 3 yrs. Comparisons of absolute and % BMD changes showed no significant difference in bone loss in FN vs SP or TH vs SP (all p values>0.05). In subsets with decrease in BMD at any site of ≥0.03 g/cm2, there remained no pattern of greater bone loss in FN vs SP (n=45) or TH vs SP (n=48). 21 declines in T-score criteria were observed, more often in spine than hip (9 SP, 6 FN, 6 TH). Of the 9 SP, 5 declined in SP only; and 3 FN and 2 TH declined without change in SP. Pelvic RT + LT-ADT for advanced PrCa was not associated with greater BMD decrease in the FN/TH (RT exposed) versus lumbar SP (not RT exposed). These preliminary results challenge the notion that the primary influence of bone loss and potential skeletal events in patients treated with RT + LT-ADT is due to the contributions of RT when LT-ADT is used; and should be verified prospectively.