From the SIR Residents and Fellows Sections (SIRRFS)
Teaching Topic: CT–Guided Bone Biopsies in Metastatic Castration-Resistant Prostate Cancer: Factors Predictive of Maximum Tumor Yield.
Holmes MG, Foss E, Joseph G, Foye A, et al. CT–Guided Bone Biopsies in Metastatic Castration-Resistant Prostate Cancer: Factors Predictive of Maximum Tumor Yield. J Vasc Interv Radiol. 2017. 28:1073-1081.
Click here for abstract
Patients with metastatic prostate cancer undergo biopsy for histological as well as molecular analysis after treatment failure. Prior studies have not addressed the factors that determine adequacy of biopsy samples especially as they relate to molecular analysis. This study was done as part of a larger multi-center study to evaluate mechanisms of resistance in metastatic castrate-resistant prostate cancer (mCRPC). The main purpose was to assess the overall success rates for histological and molecular analysis of CT guided bone biopsies performed for mCRPC. The secondary purpose was to evaluate the clinical, imaging, and technical factors that improved diagnostic yields in this cohort.
72 patients who underwent 80 CT-guided biopsies were analyzed as part of this study. Patients included in this study had histologically confirmed prostate cancer, metastatic disease amenable to image guided biopsy, and disease progression in light of biochemical castration. Successful biopsy was defined as ≥ 5% tumor on histological evaluation (80 biopsy samples) and adequate sample for next-generation sequencing (55 biopsy samples). All procedures were performed with CT guidance by four MSK trained radiologists. Biopsy sites were chosen by the operator; all sites of prior external beam radiation therapy were excluded. Clinical factors evaluated as part of the study included hemoglobin levels, PSA, lactate dehydrogenase, and alkaline phosphatase one month around the time of biopsy. Additionally, the authors also evaluated use of bone-modifying agents and length of therapy, second line therapy (immunotherapy & chemotherapy), androgen deprivation therapy, and external beam radiation. Imaging factors in the study included anatomic location of the biopsy specimen (ilium, pelvis, extrapelvis), size of lesion in cm (<2, 2-4 , >4), qualitative analysis of the lesion (dense sclerosis, subtle sclerosis, mix of dense and subtle sclerosis, or radiolucent lesions), lesion margins (ill-defined, well-circumscribed), and interval growth (>25% over past two years). Technical factors included location of the sample (central versus peripheral), quantitative attenuation at biopsy site, type of biopsy needle, distance of biopsy sample from cortex to lesion edge, and number of core samples (≤2, 3, 4, ≥ 5).
The overall success rate was 69% for histological evaluation and 64% for molecular evaluation. The only clinical variable associated with success for biopsy was alkaline phosphatase > 110 U/L (83% compared to 50% for <110 U/L). Imaging features associated with increased yield included lesions with mixed density and lucent lesions, lesions with mean attenuation ≤ 475 at biopsy site, lesions with ill-defined margins, and lesions with >25% growth in the last two years. There were no technical parameters that reached statistical significance for biopsy success. However, a distance of 1.6 cm of the lesion from cortex and peripheral location of the sample resulted in statistical trend towards significance. The location of the lesion, the specific biopsy system or the number of core samples did not meet statistical significance. There was a 20% difference in the biopsy success rate between ≤2 core and three core samples (56% to 76%) but this did not reach statistical significance.
• According to the study what imaging findings, aside from safety, are important when selecting a target lesion for patients with mCRPC undergoing molecular testing?
• The imaging characteristics which lead to statistically improved yields included lesions that are less densely sclerotic, areas in the lesion with HU < 475, lesions with ill-defined margins, and lesions that have demonstrated at least 25% growth over the prior two years if imaging is available. Study by Sprtizer et al. had similar findings in regards to imaging findings that resulted in increased yield for biopsy sample. Some of the proposed reasons for decreased diagnostic yield in more sclerotic areas potentially stem from crushed bones damaging viable tumor and difficulty in processing the more densely sclerotic samples for hematoxylin-eosin staining.
• At the genitourinary tumor board a patient with castration resistant metastatic prostate cancer is presented and the team wants to pursue targeted therapy. The team asks you as the interventional radiologist what is the likelihood of successful biopsy for next generation sequencing?
• Adequate sample for molecular analysis depends on multiple factors including clinical findings, lesion characteristics, and technical parameters (including the experience of the interventional radiologist). In the current literature the likelihood of gaining adequate sample for molecular analysis is between 40% to 64% according to Spritzer et al. and the current study.
Questions to Consider
What impact does size of the lesion have on biopsy success rates?
Even though the biopsy success rates were not statistically different based on size of the lesion (<2, 2-4 , >4), there was a step-wise increase in biopsy success rates with increase in lesion size. From a practical perspective holding all other parameters the same, a large lesion is generally easier to target. Failure to reach statistical significance may be related to smaller cohorts.
What is the role of non-image guided biopsies in patients with metastatic prostate cancer?
Approximately 90% of patients with advanced prostate cancer will have boney metastatic disease. There are some centers/clinicians who perform non-image guided biopsies, of the iliac crest in patients with metastatic disease with reported success rates between 25% to 47%. However, the success rates for these biopsies is defined by histologic evaluation and not based on isolation of molecular tissues. With improvement in imaging, especially with prostate-specific membrane antigen PET/CTs , the clinically significant question is not whether these patients have metastatic disease but what is the next step in management. For this question to be answered biopsy needs to be obtained for molecular analysis and this is where “blind” biopsies fall short.
Spritzer CE, Afonso PD, Vinson EN, et al. Bone marrow biopsy: RNA isolation with expression profiling in men with metastatic castration- resistant prostate cancer—factors affecting diagnostic success. Radiology 2013; 269:816–823.
Lorente D, Omlin A, Zafeiriou Z, et al. Castration-resistant prostate cancer tissue acquisition from bone metastases for molecular analyses. Clin Genitourin Cancer 2016; 14:485–493.
Jehan L Shah, MD
Diagnostic Radiology Resident, PGY-4
University of Florida, Department of Radiology. Gainesville, Florida.