Castration-Resistant Prostate Cancer Tissue Acquisition From Bone Metastases for Molecular Analyses

David Lorente, Aurelius Omlin, Zafeiris Zafeiriou, Daniel Nava-Rodrigues, Raquel Pérez-López, Carmel Pezaro, Niven Mehra, Elizabeth Sheridan, Ines Figueiredo, Ruth Riisnaes, Susana Miranda, Mateus Crespo, Penny Flohr, Joaquín Mateo, Amelia Altavilla, Roberta Ferraldeschi, Diletta Bianchini, Gerhardt Attard, Nina Tunariu, Johann de Bono, David Lorente, Aurelius Omlin, Zafeiris Zafeiriou, Daniel Nava-Rodrigues, Raquel Pérez-López, Carmel Pezaro, Niven Mehra, Elizabeth Sheridan, Ines Figueiredo, Ruth Riisnaes, Susana Miranda, Mateus Crespo, Penny Flohr, Joaquín Mateo, Amelia Altavilla, Roberta Ferraldeschi, Diletta Bianchini, Gerhardt Attard, Nina Tunariu, Johann de Bono

Abstract

Background: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Biopsy; Bone marrow; Computed tomography; Hounsfield units; Molecular biology.

Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Computed Tomography Parameters in the Posterior Iliac Crest
Figure 2
Figure 2
Hematoxylin and Eosin Staining of a Positive Bone Marrow Biopsy
Figure 3
Figure 3
Receiver Operating Characteristic Curve Analysis of the Test and Validation Sets

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Source: PubMed

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