Bone biopsy protocol for advanced prostate cancer in the era of precision medicine

Cancer. 2018 Mar 1;124(5):1008-1015. doi: 10.1002/cncr.31173. Epub 2017 Dec 19.


Background: Metastatic biopsies are increasingly being performed in patients with advanced prostate cancer to search for actionable targets and/or to identify emerging resistance mechanisms. Due to a predominance of bone metastases and their sclerotic nature, obtaining sufficient tissue for clinical and genomic studies is challenging.

Methods: Patients with prostate cancer bone metastases were enrolled between February 2013 and March 2017 on an institutional review board-approved protocol for prospective image-guided bone biopsy. Bone biopsies and blood clots were collected fresh. Compact bone was subjected to formalin with a decalcifying agent for diagnosis; bone marrow and blood clots were frozen in optimum cutting temperature formulation for next-generation sequencing. Frozen slides were cut from optimum cutting temperature cryomolds and evaluated for tumor histology and purity. Tissue was macrodissected for DNA and RNA extraction, and whole-exome sequencing and RNA sequencing were performed.

Results: Seventy bone biopsies from 64 patients were performed. Diagnostic material confirming prostate cancer was successful in 60 of 70 cases (85.7%). The median DNA/RNA yield was 25.5 ng/μL and 16.2 ng/μL, respectively. Whole-exome sequencing was performed successfully in 49 of 60 cases (81.7%), with additional RNA sequencing performed in 20 of 60 cases (33.3%). Recurrent alterations were as expected, including those involving the AR, PTEN, TP53, BRCA2, and SPOP genes.

Conclusions: This prostate cancer bone biopsy protocol ensures a valuable source for high-quality DNA and RNA for tumor sequencing and may be used to detect actionable alterations and resistance mechanisms in patients with bone metastases. Cancer 2018;124:1008-15. © 2017 American Cancer Society.

Keywords: DNA; RNA; biopsy; bone metastases; next-generation sequencing (NGS); precision medicine; prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / genetics
  • Bone Neoplasms / secondary*
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / metabolism
  • Bone and Bones / pathology*
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Image-Guided Biopsy
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods
  • Precision Medicine / methods
  • Prospective Studies
  • Prostate / diagnostic imaging
  • Prostate / metabolism
  • Prostate / pathology*
  • Prostatic Neoplasms / diagnostic imaging
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*