title: Castration-Resistant Prostate Cancer Tissue Acquisition From Bone Metastases for Molecular Analyses.
abstract: The urgent need for castration-resistant prostate cancer molecular characterization to guide treatment has been constrained by the disease's predilection to metastasize primarily to bone. We hypothesized that the use of clinical and imaging criteria could maximize tissue acquisition from bone marrow biopsies (BMBs). We aimed to develop a score for the selection of patients undergoing BMB.
  
  
  
  A total of 115 BMBs were performed in 101 patients: 57 were included in a derivation set and 58 were used as the validation set. The clinical and laboratory data and prebiopsy computed tomography parameters (Hounsfield units [HUs]) were determined. A score for the prediction of biopsy positivity was developed from logistic regression analysis of the derivation set and tested in the validation set.
  
  
  
  Of the 115 biopsy specimens, 75 (62.5%) were positive; 35 (61.4%) in the test set and 40 (69%) in the validation set. On univariable analysis, hemoglobin (P = .019), lactate dehydrogenase (P = .003), prostate-specific antigen (P = .005), and mean HUs (P = .004) were selected. A score based on the LDH level (≥ 225 IU/L) and mean HUs (≥ 125) was developed in multivariate analysis and was associated with BMB positivity in the validation set (odds ratio, 5.1; 95% confidence interval, 1.9%-13.4%; P = .001). The area under the curve of the score was 0.79 in the test set and 0.77 in the validation set.
  
  
  
  BMB of the iliac crest is a feasible technique for obtaining tumor tissue for genomic analysis in patients with castration-resistant prostate cancer metastatic to the bone. A signature based on the mean HUs and LDH level can predict a positive yield with acceptable internal validity. Prospective studies of independent cohorts are needed to establish the external validity of the score.
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: David
authors.initials: D
authors.lastname: Lorente
authors.affiliation: Oncohematology Department, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Aurelius
authors.initials: A
authors.lastname: Omlin
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: Zafeiris
authors.initials: Z
authors.lastname: Zafeiriou
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Nava-Rodrigues
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: Raquel
authors.initials: R
authors.lastname: Pérez-López
authors.affiliation: Eastern Health Medicine School, Monash University, Box Hill, VC, Australia.
authors.forename: Carmel
authors.initials: C
authors.lastname: Pezaro
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: Niven
authors.initials: N
authors.lastname: Mehra
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sheridan
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: Ines
authors.initials: I
authors.lastname: Figueiredo
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Riisnaes
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: Susana
authors.initials: S
authors.lastname: Miranda
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: Mateus
authors.initials: M
authors.lastname: Crespo
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: Penny
authors.initials: P
authors.lastname: Flohr
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Mateo
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: Amelia
authors.initials: A
authors.lastname: Altavilla
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ferraldeschi
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: Diletta
authors.initials: D
authors.lastname: Bianchini
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Attard
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.
authors.forename: Nina
authors.initials: N
authors.lastname: Tunariu
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK. Electronic address: johann.de-Bono@icr.ac.uk.
authors.forename: Johann
authors.initials: J
authors.lastname: de Bono
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology*; D001856:Bone Marrow Examination; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000556:secondary*; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000378:metabolism; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism / Q000473:pathology*; D014057:Tomography, X-Ray Computed
chemical_list: D014408:Biomarkers, Tumor; D007770:L-Lactate Dehydrogenase; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Biopsy; Bone marrow; Computed tomography; Hounsfield units; Molecular biology