Abstract
For individual treatment decisions in patients with metastatic prostate cancer (mPC), molecular diagnostics are increasingly used. Bone metastases are frequently the only source for obtaining metastatic tumor tissue. However, the success rate of CT-guided bone biopsies for molecular analyses in mPC patients is approximately only 40%. PET using 68Ga prostate-specific membrane antigen (68Ga-PSMA) is a promising tool to improve the harvest rate of bone biopsies for molecular analyses. The aim of this study was to determine the success rate of 68Ga-PSMA-guided bone biopsies for molecular diagnostics in mPC patients. Methods: Within a prospective multicenter whole-genome sequencing trial (NCT01855477), 69 mPC patients underwent 68Ga-PSMA PET/CT before bone biopsy. The primary endpoint was the success rate (tumor percentage ≥ 30%) of 68Ga-PSMA-guided bone biopsies. At biopsy sites, 68Ga-PSMA uptake was quantified using rigid-body image registration of 68Ga-PSMA PET/CT and interventional CT. Actionable somatic alterations were identified. Results: The success rate of 68Ga-PSMA-guided biopsies for molecular analyses was 70%. At biopsy sites categorized as positive, inconclusive, or negative for 68Ga-PSMA uptake, 70%, 64%, and 36% of biopsies were tumor-positive (≥30%), respectively (P = 0.0610). In tumor-positive biopsies, 68Ga-PSMA uptake was significantly higher (P = 0.008), whereas radiodensity was significantly lower (P = 0.006). With an area under the curve of 0.84 and 0.70, both 68Ga-PSMA uptake (SUVmax) and radiodensity (mean Hounsfield units) were strong predictors for a positive biopsy. Actionable somatic alterations were detected in 73% of the sequenced biopsies. Conclusion: In patients with mPC, 68Ga-PSMA PET/CT improves the success rate of CT-guided bone biopsies for molecular analyses, thereby identifying actionable somatic alterations in more patients. Therefore, 68Ga-PSMA PET/CT may be considered for guidance of bone biopsies in both clinical practice and clinical trials.
Highlights
2018, prostate cancer is one of the most common malignancies in men and the fifth leading cause of cancer-related death worldwide [1]
To improve the yield of bone biopsies in metastatic prostate cancer (mPC) patients, biopsies could be obtained from bone metastases, which express prostate-specific membrane antigen (PSMA)
We evaluated the potential impact of these molecular analyses on clinical decision making in mPC patients
Summary
2018, prostate cancer is one of the most common malignancies in men and the fifth leading cause of cancer-related death worldwide [1]. Molecular analyses on CT-guided bone biopsies from prostate cancer are less feasible, as the success rate is only 39%–44% and 36.5% for RNA analysis and whole-exome sequencing, respectively [7,8,10]. To improve the yield of bone biopsies in mPC patients, biopsies could be obtained from bone metastases, which express prostate-specific membrane antigen (PSMA). Fused images of 68Ga-PSMA PET/CT and diffusionweighted MRI, in combination with cone-beam CT guidance, have been applied to guide bone biopsies in patients with prostate cancer. This pilot study was performed on only a small number of. We evaluated the potential impact of these molecular analyses on clinical decision making in mPC patients
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