Added Value of Whole-Body Diffusion-Weighted Imaging in Patients Undergoing Prostate-Specific Membrane Antigen Positron Emission Tomography

<b>Background/Objectives</b>: Patients with metastatic castration-resistant prostate cancer (mCRPC) who have Prostate-Specific Membrane Antigen (PSMA)-negative disease have inferior outcomes with radioligand therapy (RLT). The objective of this study is to assess the added value of whole-body (WB) diffusion-weighted imaging (DWI) to PSMA PET for identifying PSMA-negative disease, which is important for risk stratification. <b>Methods</b>: Consecutive PSMA PET/MRI exams at our institution, which included WB DWI in patients with mCRPC, were retrospectively reviewed. For both WB DWI and PSMA PET, two independent readers scored 14 anatomic locations, which were considered positive only if both readers identified lesions. The proportion of patients with mismatched disease was summarized descriptively for each anatomic location and overall. The inter-reader agreement was computed with intra-class correlation coefficients (ICCs). <b>Results</b>: The study included 41 patients (with a mean age of 71.9 years), and WB DWI identified PSMA-negative lesions in 24% of patients. PSMA PET had higher agreement than DWI, although both had good agreement (ICC: 0.87 and 0.72, respectively). The median overall survival was 442 days in those with mismatched disease vs. 523 days in those without, although this difference is not statistically significant (<i>p</i> = 0.49). <b>Conclusions</b>: The addition of WB DWI to PSMA PET can identify PSMA-negative disease, which could alter patient management.