Exploring New Multimodal Quantitative Imaging Indices for the Assessment of Osseous Tumor Burden in Prostate Cancer Using ⁶⁸Ga-PSMA PET/CT

Abstract

PET combined with CT and prostate-specific membrane antigen (PSMA) ligands has gained significant interest for staging prostate cancer (PC). In this study, we propose 2 multimodal quantitative indices as imaging biomarkers for the assessment of osseous tumor burden using Ga-PSMA PET/CT and present preliminary clinical data. We defined 2 bone PET indices (BPIs) that incorporate anatomic information from CT and functional information from Ga-PSMA PET: BPI is the percentage of bone volume affected by tumor and BPI additionally considers the level of PSMA expression. We describe a semiautomatic computation method based on segmentation of bones in CT and of lesions in PET. Data from 45 patients with castration-resistant PC and bone metastases during Ra-dichloride were retrospectively analyzed. We evaluated the computational stability and reproducibility of the proposed indices and explored their relation to the prostate-specific antigen blood value, the bone scan index (BSI), and disease classification using PERCIST. On the technical side, BPI and BPI showed an interobserver maximum difference of 3.5%, and their computation took only a few minutes. On the clinical side, BPI and BPI showed significant correlations with BSI ( = 0.76 and 0.74, respectively, < 0.001) and prostate-specific antigen values ( = 0.57 and 0.54, respectively, < 0.01). When the proposed indices were compared against expert rating using PERCIST, BPI and BPI showed better agreement than BSI, indicating their potential for objective response evaluation. We propose the evaluation of BPI and BPI as imaging biomarkers for Ga-PSMA PET/CT in a prospective study exploring their potential for outcome prediction in patients with bone metastases from PC.

Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE): Proposed miTNM Classification for the Interpretation of PSMA-Ligand PET/CT

“…PSMA-ligand PET enables unprecedented delineation of wholebody tumor burden based on high target-to-background expression levels (Supplemental Fig. 1) (59). Introduction of tools for whole-body tumor volumetry based on a combination of molecular and morphologic techniques might overcome several limitations of solely morphology-based criteria, such as RECIST (60): lesions without distinct morphologic boundaries, such as bone metastases, could be included in the evaluation.…”

“…Consequently, direct assessment of tumor volume, instead of assessment of lesion diameter sums, could be done. For PSMA-ligand PET, initial attempts have been made by introducing PSMAderived tumor volume, total lesion PSMA, or bone PET indices (59,61). Further advances in the field of software-assisted tumor delineation will help to automatically delineate-separately for bone and soft tissue-total tumor volume, total tumor target expression, or a combination of these.…”

qPSMA: Semiautomatic Software for Whole-Body Tumor Burden Assessment in Prostate Cancer Using 68Ga-PSMA11 PET/CT

“…The bone mask incorporates the skeleton, which is first segmented on the CT scan. The segmentation method relies on pixel intensities and different morphologic operations, as described previously (12,16). When necessary, manual corrections can subsequently be applied.…”

“…68 Ga-PSMA11 does not usually lead to relevant unspecific uptake within the skeleton. Bieth et al (12), described a separate fixed SUV threshold for soft-tissue lesions (SUV thr_st ) of 3 as useful for bone lesion segmentation to omit low background uptake. Application of this threshold is restricted to voxels within the transposed bone mask from CT. Because of the spillover effect and frequent misalignment between the CT and PET images (e.g., because of breathing), some of the bone lesions may be located outside the bone mask and consequently will be improperly segmented as soft-tissue lesions.…”

“…However, in patients with a high tumor load, manual quantification is time-consuming and a semiautomatic tool would considerably reduce the segmentation time. A first step toward a semiautomatic tumor burden assessment in prostate cancer was described by Bieth et al (12), who proposed a tool that quantifies involvement of the skeleton in prostate cancer inspired by the bone scan index using 68 Ga-PSMA11 PET/CT.…”