⁶⁸Ga-PSMA-Guided Bone Biopsies for Molecular Diagnostics in Patients with Metastatic Prostate Cancer

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 (SUV_max) 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.