Variables Associated With Bone Biopsy Tumor Yield in mCRPC
Variables Associated With Bone Biopsy Tumor Yield in mCRPC
Background Understanding the mechanisms driving disease progression is fundamental to identifying new therapeutic targets for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC). Owing to the prevalence of bone metastases in mCRPC, obtaining sufficient tumor tissue for analysis has historically been a challenge. In this exploratory analysis, we evaluated imaging, procedural and clinical variables associated with tumor yield on image-guided bone biopsy in men with mCRPC.
Methods Clinical data were collected prospectively from men with mCRPC enrolled on a phase II trial with serial metastasis biopsies performed according to standard clinical protocol. Imaging was retrospectively reviewed. We evaluated the percent positive biopsy cores (PPC), calculated as the number of positive cores divided by the total number of cores collected per biopsy.
Results Twenty-nine men had 39 bone biopsies. Seventy-seven percent of bone biopsies had at least one positive biopsy core. We determined that lesion size and distance from the skin to the lesion edge correlated with tumor yield on biopsy (median PPC 75% versus 42% for lesions >8.8 cm versus ≤8.8 cm, respectively, P=0.05; median PPC 33% versus 71% for distance ≥6.1 versus <6.1 cm, respectively, P=0.02). There was a trend towards increased tumor yield in patients with increased uptake on radionuclide bone scan, higher calcium levels and shorter duration of osteoclast-targeting therapy, although this was not statistically significant. Ten men had 14 soft tissue biopsies. All soft tissue biopsies had at least one positive biopsy core.
Conclusions This exploratory analysis suggests that there are imaging, procedural and clinical variables that have an impact on image-guided bone biopsy yield. In order to maximize harvest of prostate cancer tissue, we have incorporated a prospective analysis of the metrics described here as part of a multi-institutional project aiming to use the molecular characterization of mCRPC tumors to direct individual therapy.
Prostate cancer is a heterogeneous disease with marked variability in patient outcomes. Although curative treatments are available, over 29 000 men per year die from prostate cancer. To identify drivers of resistance and novel therapeutic targets, a better understanding of the genomic landscape of metastatic castration-resistant prostate cancer (mCRPC) is essential. Over the past decade, new laboratory techniques have accelerated the molecular characterization of prostate cancer. Currently, underway is a large multi-institutional project entitled 'Precision Therapy in Advanced Prostate Cancer' funded by Stand Up To Cancer (SU2C) that uses next-generation sequencing technologies for the molecular characterization of mCRPC tumors isolated from metastasis biopsies.
A key initial step in the molecular characterization of mCRPC involves isolation of high-quality nucleic acid from prostate cancer cells. However, acquiring sufficient tumor tissue for molecular characterization often represents a challenge because of the paucity of soft tissue metastases. In addition, prostate cancer metastases to bone frequently cause a dense sclerotic reaction and biopsies are technically challenging and associated with low yield, leading to insufficient tumor tissue for sequencing analysis.
Strategies to improve tumor yield on bone biopsy in mCRPC have been limited. The largest study comes from a 26-center trial of 184 men with mCRPC that demonstrated that 25.5% of non-image-guided bone marrow biopsies were positive for tumor by histology. Another study of 31 men with mCRPC undergoing 54 image-guided biopsies showed that 67% of samples were positive by histology.
Collecting tissue samples necessitates the development of practical methods to optimize tumor acquisition, a process that involves collaboration between radiologists, pathologists and investigators. Given limited studies delineating strategies to maximize tumor yield on bone biopsy, we embarked on this exploratory analysis to better inform tissue collection as part of the large multi-institutional project described above. In this pilot study, we evaluate variables associated with tumor yield on image-guided bone biopsy in mCRPC.
Abstract and Introduction
Abstract
Background Understanding the mechanisms driving disease progression is fundamental to identifying new therapeutic targets for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC). Owing to the prevalence of bone metastases in mCRPC, obtaining sufficient tumor tissue for analysis has historically been a challenge. In this exploratory analysis, we evaluated imaging, procedural and clinical variables associated with tumor yield on image-guided bone biopsy in men with mCRPC.
Methods Clinical data were collected prospectively from men with mCRPC enrolled on a phase II trial with serial metastasis biopsies performed according to standard clinical protocol. Imaging was retrospectively reviewed. We evaluated the percent positive biopsy cores (PPC), calculated as the number of positive cores divided by the total number of cores collected per biopsy.
Results Twenty-nine men had 39 bone biopsies. Seventy-seven percent of bone biopsies had at least one positive biopsy core. We determined that lesion size and distance from the skin to the lesion edge correlated with tumor yield on biopsy (median PPC 75% versus 42% for lesions >8.8 cm versus ≤8.8 cm, respectively, P=0.05; median PPC 33% versus 71% for distance ≥6.1 versus <6.1 cm, respectively, P=0.02). There was a trend towards increased tumor yield in patients with increased uptake on radionuclide bone scan, higher calcium levels and shorter duration of osteoclast-targeting therapy, although this was not statistically significant. Ten men had 14 soft tissue biopsies. All soft tissue biopsies had at least one positive biopsy core.
Conclusions This exploratory analysis suggests that there are imaging, procedural and clinical variables that have an impact on image-guided bone biopsy yield. In order to maximize harvest of prostate cancer tissue, we have incorporated a prospective analysis of the metrics described here as part of a multi-institutional project aiming to use the molecular characterization of mCRPC tumors to direct individual therapy.
Introduction
Prostate cancer is a heterogeneous disease with marked variability in patient outcomes. Although curative treatments are available, over 29 000 men per year die from prostate cancer. To identify drivers of resistance and novel therapeutic targets, a better understanding of the genomic landscape of metastatic castration-resistant prostate cancer (mCRPC) is essential. Over the past decade, new laboratory techniques have accelerated the molecular characterization of prostate cancer. Currently, underway is a large multi-institutional project entitled 'Precision Therapy in Advanced Prostate Cancer' funded by Stand Up To Cancer (SU2C) that uses next-generation sequencing technologies for the molecular characterization of mCRPC tumors isolated from metastasis biopsies.
A key initial step in the molecular characterization of mCRPC involves isolation of high-quality nucleic acid from prostate cancer cells. However, acquiring sufficient tumor tissue for molecular characterization often represents a challenge because of the paucity of soft tissue metastases. In addition, prostate cancer metastases to bone frequently cause a dense sclerotic reaction and biopsies are technically challenging and associated with low yield, leading to insufficient tumor tissue for sequencing analysis.
Strategies to improve tumor yield on bone biopsy in mCRPC have been limited. The largest study comes from a 26-center trial of 184 men with mCRPC that demonstrated that 25.5% of non-image-guided bone marrow biopsies were positive for tumor by histology. Another study of 31 men with mCRPC undergoing 54 image-guided biopsies showed that 67% of samples were positive by histology.
Collecting tissue samples necessitates the development of practical methods to optimize tumor acquisition, a process that involves collaboration between radiologists, pathologists and investigators. Given limited studies delineating strategies to maximize tumor yield on bone biopsy, we embarked on this exploratory analysis to better inform tissue collection as part of the large multi-institutional project described above. In this pilot study, we evaluate variables associated with tumor yield on image-guided bone biopsy in mCRPC.