Impact of skeletal-related events on survival in patients with prostate cancer metastatic to bones.

223 Background: Skeletal related events (SREs), defined as pathological fracture, spinal cord compression, surgery or radiotherapy to the bone, occur in nearly half of men diagnosed with metastatic prostate cancer. Accurate assessment of the risk of death associated with SREs is important to making decisions about the use of recently approved treatments, which have been shown to decrease the frequency of skeletal events, yet estimating the impact of SREs on survival presents several methodological challenges given the recurrent time-dependent nature of exposure. Methods: A cohort of men >65years of age, diagnosed with prostate cancer and bone metastasis between January 1, 2004 and December 31, 2009 was identified from the Surveillance Epidemiology and End Results (SEER) registries were linked to Medicare Parts A and B claims. The outcome of interest, death from any cause, was ascertained from SEER and survival time was calculated from the date of metastatic prostate cancer diagnosis. Multivariable Cox proportional hazards models treating the occurrence of an SRE as a time-dependent exposure were used to estimate the hazard ratios (HR) and corresponding 95% confidence intervals (CI) for the association between SRE occurrence, number, and type, and death. Results: Among 3,297 men with metastatic prostate cancer, 40% experienced ≥1 SRE during the observational follow-up period (median 19 months). Compared to men who remained SRE-free, cohort members who had ≥1 SREs had a two-fold higher risk of death (HR 2.2, 95% CI 2.0-2.4). Those whose first SRE was a pathological fracture had a 2.7-fold higher risk of death (HR 2.7, 95% CI 2.3-3.1), followed by spinal cord compression (HR 2.1, 95% CI 1.8-2.5), surgery (HR 1.8, 95% CI 1.5-2.2) and radiotherapy (HR 2.2, 95% CI 1.9-2.4). Compared to those experiencing only one SRE, men who experienced a second SRE of any type had double the risk of death (HR 2.2, 95% CI 1.9-2.6). Conclusions: SREs were associated with ≥50% reduction in overall survival. This finding is consistent across different types of SREs and supports using therapies to prevent or treat SREs in patients with prostate cancer metastatic to the bones.