title: Do skeletal-related events predict overall survival in men with metastatic castration-resistant prostate cancer?
abstract: 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).
  
  
  
  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.
  
  
  
  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).
  
  
  
  SREs are associated with increased mortality in men with bone mCRPC. Further studies on the impact of preventing SREs to increase survival are warranted.
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA.|Division of Urology, Department of Surgery, Veterans Affairs Medical Center, Durham, NC, USA.
authors.forename: L E
authors.initials: LE
authors.lastname: Howard
authors.affiliation: Division of Urology, Department of Surgery, Veterans Affairs Medical Center, Durham, NC, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: De Hoedt
authors.affiliation: Department of Urology, UCLA School of Medicine, Los Angeles, CA, USA.|Urology Section, Department of Surgery, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Aronson
authors.affiliation: Urology Department, University of California San Diego Health System, San Diego, CA, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Kane
authors.affiliation: Division of Urology, Department of Surgery, Oregon Health and Science University, Portland, OR, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Amling
authors.affiliation: Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Cooperberg
authors.affiliation: Section of Urology, Department of Surgery, Veterans Affairs Medical Center, Augusta, GA, USA.|Section of Urology, Department of Surgery, Medical College of Georgia, Augusta, GA, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Terris
authors.affiliation: US Health Economics, Bayer Pharmaceuticals, Whippany, NJ, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Divers
authors.affiliation: US Health Economics, Bayer Pharmaceuticals, Whippany, NJ, USA.
authors.forename: A
authors.initials: A
authors.lastname: Valderrama
authors.affiliation: Division of Urology, Department of Surgery, Veterans Affairs Medical Center, Durham, NC, USA.|Department of Surgery, Division of Urology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Freedland
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000401:mortality / Q000473:pathology* / Q000556:secondary*; D001842:Bone and Bones / Q000473:pathology*; D015331:Cohort Studies; D005598:Fractures, Spontaneous / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D064129:Prostatic Neoplasms, Castration-Resistant / Q000401:mortality* / Q000473:pathology*; D012307:Risk Factors; D013117:Spinal Cord Compression / Q000401:mortality / Q000473:pathology