The future of PSMA PET and WB MRI as next-generation imaging tools in prostate cancer

Radiolabelled prostate-specific membrane antigen (PSMA)-based PET–CT has been shown in numerous studies to be superior to conventional imaging in the detection of nodal or distant metastatic lesions. 68Ga-PSMA PET–CT is now recommended by many guidelines for the detection of biochemically relapsed disease after radical local therapy. PSMA radioligands can also function as radiotheranostics, and Lu-PSMA has been shown to be a potential new line of treatment for metastatic castration-resistant prostate cancer. Whole-body (WB) MRI has been shown to have a high diagnostic performance in the detection and monitoring of metastatic bone disease. Prospective, randomized, multicentre studies comparing 68Ga-PSMA PET–CT and WB MRI for pelvic nodal and metastatic disease detection are yet to be performed. Challenges for interpretation of PSMA include tracer trapping in non-target tissues and also urinary excretion of tracers, which confounds image interpretation at the vesicoureteral junction. Additionally, studies have shown how long-term androgen deprivation therapy (ADT) affects PSMA expression and could, therefore, reduce tracer uptake and visibility of PSMA+ lesions. Furthermore, ADT of short duration might increase PSMA expression, leading to the PSMA flare phenomenon, which makes the accurate monitoring of treatment response to ADT with PSMA PET challenging. Scan duration, detection of incidentalomas and presence of metallic implants are some of the major challenges with WB MRI. Emerging data support the wider adoption of PSMA PET and WB MRI for diagnosis, staging, disease burden evaluation and response monitoring, although their relative roles in the standard-of-care management of patients are yet to be fully defined. In this Review, the authors discuss the current evidence for the use of prostate-specific membrane antigen (PSMA) PET and whole-body (WB) MRI, consider the evolving use of PSMA PET-derived and WB MRI-derived quantitative biomarkers and make recommendations for future clinical trials of these modalities.