Factors predicting skeletal-related events in patients with bone metastatic castration-resistant prostate cancer

Cancer. 2017 May 1;123(9):1528-1535. doi: 10.1002/cncr.30505. Epub 2016 Dec 27.

Abstract

Background: Skeletal-related events (SREs) are common complications of bone metastatic castration-resistant prostate cancer (mCRPC). To the authors' knowledge, there are limited data regarding which factors predict SREs. The authors identified risk factors for SREs in men with bone mCRPC using characteristics commonly available in the medical record.

Methods: Data from 454 patients with nonmetastatic CRPC were identified from 2 Veteran Affairs Medical Centers from 2000 through 2013. Among these men, 233 (51%) developed bone metastases during follow-up and represented the study cohort. First occurrence of an SRE was abstracted from the medical records. A stepwise multivariable Cox model was used to select the strongest predictors of time to SRE.

Results: The median age of the patients at the time of diagnosis of bone mCRPC was 75 years (interquartile range, 68-81 years), and there were 153 nonblack patients (66%). During follow-up (median, 7.8 months [interquartile range, 2.9-18.3 months]), 88 patients (38%) had an SRE. On univariable analysis, more recent year of metastasis (hazard ratio [HR], 0.91), prostate-specific antigen doubling time of ≥9 months versus <9 months (HR, 0.50), and bone pain (HR, 3.34) were all found to be associated with SRE risk. On multivariable analysis, year of metastasis (HR, 0.93), biopsy Gleason score of 7 versus ≤6 (HR, 1.74), radiotherapy as the primary localized treatment versus none (HR, 2.33), and bone pain (HR, 3.64) were associated with SRE risk. The area under the curve for a multivariable model based upon these risk factors was 0.744.

Conclusions: The authors identified several significant predictors of SREs among men with mCRPC. In particular, men with bone pain are at high risk of an SRE. If confirmed, future trials should focus on prolonging life and reducing SRE risk in patients with mCRPC with bone pain. Cancer 2017;123:1528-1535. © 2017 American Cancer Society.

Keywords: bone metastases; bone pain; metastatic castration-resistant prostate cancer (mCRPC); prostate cancer; skeletal-related event (SRE).

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bone Neoplasms / blood
  • Bone Neoplasms / epidemiology*
  • Bone Neoplasms / secondary
  • Bone Neoplasms / therapy
  • Bone and Bones / surgery
  • Follow-Up Studies
  • Fractures, Spontaneous / epidemiology*
  • Humans
  • Kallikreins / blood
  • Male
  • Multivariate Analysis
  • Neoplasm Grading
  • Orthopedic Procedures / statistics & numerical data
  • Pain / epidemiology*
  • Proportional Hazards Models
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / blood
  • Prostatic Neoplasms, Castration-Resistant / epidemiology*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Radiotherapy / statistics & numerical data
  • Retrospective Studies
  • Risk Factors
  • Spinal Cord Compression / epidemiology*

Substances

  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen