Variation in guideline-concordant use of bone modifying agents for prostate cancer.

39 Background: Skeletal related events (SREs) are a set of morbidities resulting from metastatic bone disease, including pathologic fracture, spial cord compression, and others. Clinical practice guidelines recommend use of bone modifying agents (BMAs) to prevent SREs for patients with metastatic castration resistant prostate cancer (mCRPC), and against their use for SRE prevention in metastatic castration sensitive prostate cancer (mCSPC). Whether these drugs are delivered in a consistent, guideline-concordant manner across oncology providers has not been described. Methods: We conducted a multicenter, retrospective, cohort study of patients diagnosed with prostate cancer metastatic to bone during 2020-21. The sample included three large health systems in the US Northeast (two community-based networks and one academic cancer center), collectively employing > 1700 physicians and treating > 800 cases of high-risk and/or metastatic prostate cancer each year. Patient comorbidities, timing of emergence of CRPC, and dates of BMA initiation (zoledronic acid or denosumab) were ascertained via chart review. The primary outcomes were BMA overuse during CSPC (defined as BMA initiation prior to emergence of CRPC, among patients without a comorbid condition for which BMA therapy may be appropriate: osteoporosis, osteopenia, or osteoporotic fracture) and appropriate use during CRPC (defined as BMA initiation subsequent to emergence of CRPC). Results: There were 153 eligible patients, 51 from each health system. The median age was 72 years (IQR 65, 80), PSA at diagnosis was 110 (IQR 16, 720), and time from diagnosis to development of CRPC was 352 days (IQR 224, 453). At diagnosis, 14 (9%) patients had documented osteoporosis or osteopenia and 22 (14%) had prior osteoporotic fracture. Among 106 patients assessable for overuse during CSPC, 17 (16%) received BMA (ranging from 13%-21% among the three systems). Among 65 patients who developed CRPC, 32 (44%) had initiated BMA therapy prior to death or most recent follow-up. There was greater variation in use during CRPC, ranging from 22%-54% across the three systems. In time-to-event analysis, at 2 years after emergence of CRPC 52% of surviving patients had initiated BMA therapy (ranging from 30%-66% among the three systems). Conclusions: Overuse of BMAs appeared consistently low. However, guideline-concordant use for patients with metastatic CRPC may vary substantially among clinicians and healthcare systems. This degree of variation suggests that some patients with mCRPC who may benefit from BMA therapy do not receive it. Interventions to reduce these discrepancies and increase appropriate care may improve patient outcomes.