Do skeletal-related events predict overall survival in men with metastatic castration-resistant prostate cancer?

• Published in: Prostate cancer and prostatic diseases 2016-12, Vol.19 (4), p.380-384
• Main Authors: Howard, L E, De Hoedt, A M, Aronson, W J, Kane, C J, Amling, C L, Cooperberg, M R, Terris, M K, Divers, C H, Valderrama, A, Freedland, S J
• Format: Article
• Language: English
• Subjects: 692/308/409; 692/699/67/589/466; Biomedical and Life Sciences; Biomedicine; Biopsy; Bone cancer; Bone surgery; Bone tumors; California; Cancer metastasis; Cancer Research; Cancer therapies; Castration; Complications and side effects; Compression; Confidence intervals; Data collection; Denosumab; Dependent variables; Deprivation; Development and progression; Health aspects; Health services; Medical records; Metastases; Metastasis; Mortality; original-article; Pain; Patient outcomes; Prognosis; Prostate cancer; Quality of life; Radiation; Risk analysis; Risk factors; Secondary analysis; Spinal cord; Survival; Time dependence; Zoledronic acid
• ISSN: 1365-7852; 1476-5608
• DOI: 10.1038/pcan.2016.26

Background: Skeletal-related events (SREs) including pathologic fracture, spinal cord compression, radiation to bone and surgery to bone, are common in men with bone metastatic castration-resistant prostate cancer (mCRPC). Men with mCRPC are at high risk of death. Whether SREs predict mortality is unclear. We tested the association between SREs and overall survival (OS) in a multiethnic cohort with bone mCRPC, controlling for key covariates unavailable in claims data such as bone pain, number of bone metastases and PSA doubling time (PSADT). Methods: We collected data on 233 men diagnosed with nonmetastatic castration-resistant prostate cancer (CRPC) in 2000–2013 at two Veterans Affairs hospitals who later progressed to bone metastases. First occurrence of SRE and OS were collected from the medical records. Cox models were used to test the association between SRE and OS, treating SRE as a time-dependent variable. We adjusted for age, year, race, treatment center, biopsy Gleason, primary treatment to the prostate, PSA, PSADT, months from androgen deprivation therapy to CRPC, months from CRPC to metastasis and number of bone metastases at initial bone metastasis diagnosis. In a secondary analysis, we also adjusted for bone pain. Results: During follow-up, 88 (38%) patients had an SRE and 198 (85%) died. After adjusting for risk factors, SRE was associated with increased mortality (hazard ratio (HR)=1.67; 95% confidence interval (CI) 1.22–2.30; P =0.001). When bone pain was added to the model, the association of SREs and OS was attenuated, but remained significant (HR=1.42; 95% CI 1.01–1.99; P =0.042). Conclusions: SREs are associated with increased mortality in men with bone mCRPC. Further studies on the impact of preventing SREs to increase survival are warranted.