Reasons for Discordance between ⁶⁸Ga-PSMA-PET and Magnetic Resonance Imaging in Men with Metastatic Prostate Cancer

Background: PSMA PET has emerged as a "gold standard" imaging modality for assessing prostate cancer metastases. However, it is not universally available, and this limits its impact. In contrast, whole-body MRI is much more widely available but misses more lesions. This study aims to improve the interpretation of whole-body MRI by comparing false negative scans retrospectively to PSMA PET.

Methods: This study was a retrospective sub-analysis of a prospectively collected database of patients who participated in a clinical trial of PSMA PET/MRI comparing PSMA PET and whole-body MRI from 2018-2021. Subjects whose separately read PSMA PET and MRI diagnostic reports showed discrepancies ("false negative" MRI cases) were selected for sub-analysis. The cases were reviewed by the same attending radiologist who originally read the scans. The radiologist noted specific features on MRI indicating metastatic disease that were initially missed.

Results: Of 263 cases, 38 (14%) met the inclusion criteria and were reviewed. Six classes of mpMRI false negatives were identified: anatomically normal (18, 47%), atypical MRI appearance (6, 16%), mischaracterization (1, 3%), undercall (6, 16%), obscured (4, 11%), and no abnormality on MRI (3, 8%). Considering that the atypical and undercalled cases could have been adjusted in retrospect, and that 4 additional cases had positive lesions to the same extent and 11 further cases had disease confined to the pelvis, only 11 (4%) of the original 263 would have had disease outside of a conventional radiation treatment plan.

Conclusion: Notably, almost 50% of the cases, including most lymph node metastases, were anatomically normal using standard criteria. This suggests that current anatomic criteria for evaluating prostate cancer lymph node metastases are not ideal, and there is a need for improved criteria. In addition, 32% of cases involved some element of human interpretive error, and, therefore, improving reader training may lead to more accurate results.