68Ga-PSMA-PET/CT and Diffusion MRI Targeting for Cone-Beam CT-Guided Bone Biopsies of Castration-Resistant Prostate Cancer Patients

Abstract

Introduction Precision medicine expands the treatment options for metastatic castration-resistant prostate cancer (mCRPC) by targeting druggable genetic aberrations. Aberrations can be identified following molecular analysis of metastatic tissue. Bone metastases, commonly present in mCRPC, hinder precision medicine due to a high proportion of biopsies with insufficient tumor cells for nextgeneration DNA sequencing. We aimed to investigate the feasibility of incorporating advanced target planning and needle guidance in bone biopsies and whether this procedure increases biopsy tumor yield and success rate of molecular analysis as compared to the current standards, utilizing only CT guidance. Materials and Methods In a pilot study, ten mCRPC patients received 68 Ga-prostate-specific membrane antigen (PSMA)-PET/CT and diffusion-weighted MRI as biopsy planning images. These datasets were fused for targeting metastatic lesions with high tumor densities. Biopsies were performed under cone-beam CT (CBCT) guidance. Feasibility of target planning and needle guidance was assessed, and success of molecular analysis and tumor yield were reported. Results Fusion target planning and CBCT needle guidance were feasible. Nine out of ten biopsies contained prostate cancer cells, with a median of 39% and 40% tumor cells by two different sequencing techniques. Molecular analysis was successful in eight of ten patients (80%). This exceeds previous reports on CT-guided biopsies that ranged from 33 to 44%. In two patients, important druggable aberrations were found. Discussion A biopsy procedure using advanced target planning and needle guidance is feasible and can increase the success rate of molecular analysis in bone metastases, thereby having the potential of improving treatment outcome for patients with mCRPC. Level of Evidence Level 4, case series.

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

“…Recently, fused images of 68 Ga-PSMA PET/CT and diffusion weighted MRI, in combination with conebeam CT guidance, have been applied to guide bone biopsies in patients with prostate cancer. Though in a small number of patients (N=10), this pilot study showed a success rate of 80% (14). Therefore, 68 Ga-PSMA PET/CT is a promising technique to increase the success rate of bone biopsies for molecular analyses in prostate cancer patients.…”

Prior PSMA PET-CT Imaging and Hounsfield Unit Impact on Tumor Yield and Success of Molecular Analyses from Bone Biopsies in Metastatic Prostate Cancer

“…Another retrospective multicenter study indicated that both HU mean and SUV max variables from CT and 68 Ga-PSMA PET imaging, associate with an outcome of at least 30% tumor content in bone biopsies [ 21 ]. In a previous published prospective study of ten mCRPC patients, advanced planning with 68 Ga-PSMA PET and diffusion-weighted MRI increased diagnostic yield up to 90% on cone-beam CT-guided biopsy [ 26 ]. Further prospective studies are needed to assess and validate radiomic signatures to predict bone biopsy outcome utilizing CT, MRI and PSMA PET imaging modalities.…”

Multiparametric bone MRI can improve CT-guided bone biopsy target selection in cancer patients and increase diagnostic yield and feasibility of next-generation tumour sequencing

“…To compensate for the shortcomings of CT, some authors advocate using PET/CT to identify bone biopsy targets [ 15 , 16 ]. Recently published data on using prostate-specific membrane antigen (PSMA)-PET/CT for bone biopsy targeting in prostate cancer patients improved NGS feasibility rates up to 70–90% [ 12 , 17 , 18 ]. Remarkably, although being recognised as the gold standard imaging method for detecting malignant bone diseases, MRI features that are associated with a positive bone biopsy or NGS outcome have not been described [ 19 , 20 ].…”