Imaging, procedural and clinical variables associated with tumor yield on bone biopsy in metastatic castration-resistant prostate cancer

McKay, Rana R.; Zukotynski, Katherine; Werner, Lillian; Voznesensky, Olga; Wu, Jim S.; Smith, Stacy E.; Jiang, Zhenyang; Melnick, Kevin; Yuan, Xin; Kantoff, Philip W.; Montgomery, Bruce; Balk, Steven P.; Taplin, Mary‐Ellen

doi:10.1038/pcan.2014.28

Cited by 33 publications

(44 citation statements)

References 12 publications

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“…Thus, a large proportion of patients do not have soft tissue metastases amenable for biopsy. A number of studies published in the past decade have reported variable rates of positive BMBs ranging from 25% to 50% for nonimaging-guided biopsies16, 17, 20 and increasing to 67% to 77% when performed under direct CT guidance 15, 21. Our cohort, with biopsies performed without direct CT guidance, had a bone biopsy positivity rate of 62.5%, consistent with the findings from previous reports.…”

Section: Discussionsupporting

confidence: 89%

“…Previous studies have established associations among the clinical, analytical, and CT parameters with BMB positivity 16, 21. The present study, however, is the first study to establish the value of the widely used CT and analytical parameters and develop a score with direct applicability in the clinical setting, with validation of these results in a separate control group.…”

Section: Discussionmentioning

confidence: 78%

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

Lorente

Omlin

Nava-Rodrigues

et al. 2016

Clinical Genitourinary Cancer

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Micro-AbstractWe analyzed 115 iliac crest bone marrow biopsy specimens from 101 patients with metastatic castration-resistant prostate cancer, divided into a test (n = 57) and a validation (n = 58) set. We developed a score based on computed tomography Hounsfield units and lactate dehydrogenase levels, which were associated with a positive biopsy result. The score can be used to select patients for whom a bone marrow biopsy will provide tissue for molecular characterization.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 78%

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

Lorente

Omlin

Nava-Rodrigues

et al. 2016

Clinical Genitourinary Cancer

View full text Add to dashboard Cite

show abstract

“…Historically, this process has been a challenge given the paucity of soft tissue metastases and dense sclerotic reaction associated with bone metastases, making biopsies and tissue processing technically difficult resulting in low tumor yield. We previously demonstrated that imaging, procedural, and clinical variables have an impact on image-guided bone biopsy tumor yield and this work demonstrates that bone biopsy in metastatic CRPC is feasible resulting in sufficient tumor yield in 80% of samples for correlative assessment (41). …”

Section: Discussionmentioning

confidence: 88%

A Phase II Trial of Abiraterone Combined with Dutasteride for Men with Metastatic Castration-Resistant Prostate Cancer

McKay

Werner

Mostaghel

et al. 2017

Clinical Cancer Research

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Purpose Despite the efficacy of abiraterone, a CYP17A1 inhibitor, in metastatic castration-resistant prostate cancer (CRPC), nearly all patients develop resistance. The purpose of this phase II study was to evaluate mechanisms of resistance to more complete androgen synthesis inhibition with abiraterone and dutasteride. Experimental Design Eligible metastatic CRPC patients underwent a baseline metastasis biopsy. Patients received abiraterone and prednisone for two 4-week cycles. After this time, high-dose dutasteride (3.5mg daily) was added. Patients continued therapy until study withdrawal or radiographic progression. Repeat metastasis biopsy was obtained at progression. The primary endpoint was to assess mechanisms of resistance. Serum hormone and abiraterone levels were assessed. Tissue was assessed for androgen receptor (AR) and AR splice variant-7 (ARV7) expression. Results Forty patients were enrolled. 60% (n=24) achieved a ≥50% reduction in PSA. The median time to radiographic progression was 11 months. Nearly all baseline (n=29/30) and post-treatment (n=16/16) tumors tested for AR nuclear expression were positive. Of those tested, ARV7 expression was present in 48% (n=10/21) of baseline and 42% (n=5/12) of treatment discontinuation specimens. Compared to patients with higher serum abiraterone levels at treatment discontinuation, patients with lower levels had higher circulating androgens. Conclusions Despite increased androgen synthesis inhibition, we demonstrate that tumor AR axis remains important in disease progression. We highlight that abiraterone metabolism and pharmacokinetics may play a role in resistance. The non-comparative design limits conclusions on the efficacy of dual therapy with abiraterone and dutasteride, but the results support development of further multifaceted approaches towards AR inhibition.

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“…Metastatic biopsies have been challenged by a predominance of sclerotic bone lesions, which are technically challenging and harbor limited viable tissues for extensive analyses. Nonetheless, in recent years through collaborative efforts and clinical trials, biopsies in metastatic prostate cancer have become feasible [12]. Tumor biopsy programs including those from the Stand Up To Cancer (SU2C)- Prostate Cancer Foundation (PCF) Dream Team clinical trials [13, 14] have revealed 1) genomic diversity between patients with CRPC; 2) acquisition and/or enrichment of molecular alterations in CRPC compared to primary prostate cancer; 3) emergence of pathologic variants including atypical and neuroendocrine phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Emerging Variants of Castration-Resistant Prostate Cancer

2017

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Metastatic castration resistant prostate cancer (CRPC) is associated with substantial clinical, pathologic, and molecular heterogeneity. Most tumors remain driven by androgen receptor (AR) signaling, which has clinical implications for patient selection for AR-directed approaches. However, histologic and clinical resistance phenotypes can emerge after AR-inhibition, in which the tumors become less dependent on the AR. In this review we discuss prostate cancer variants including neuroendocrine (NEPC) and aggressive variant (AVPC) prostate cancers and their clinical implications. Improvements in the understanding of the biologic mechanisms and molecular features underlying prostate cancer variants may help prognostication and facilitate the development of novel therapeutic approaches for subclasses of patient with CRPC.

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Imaging, procedural and clinical variables associated with tumor yield on bone biopsy in metastatic castration-resistant prostate cancer

Cited by 33 publications

References 12 publications

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

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

A Phase II Trial of Abiraterone Combined with Dutasteride for Men with Metastatic Castration-Resistant Prostate Cancer

Emerging Variants of Castration-Resistant Prostate Cancer

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