Small-molecule ligands that bind to the cell-surface prostate-specific membrane antigen (PSMA) have been widely used for positron emission tomography (PET). Compared to the recently approved 18F-Fluciclovine-PET, PSMA-PET had higher accuracy in initial staging and biochemical recurrence of prostate cancer.1, 2, 3 In patients with high-risk castration-resistant prostate cancer (CRPC) without evidence of distant metastasis on conventional imaging (ie, bone scan or CT), PSMA-PET could detect metastases in more than 50% of patients.4 Polymetastatic disease extent based on PSMA-PET and PSMA avidity were prognostic factors adversely impacting overall survival.5 Also, PSMA-PET detected a greater number of lesions in metastatic CRPC (mCRPC) patients when compared with bone scan.6 Therefore, the U.S. Food and Drug Administration (FDA) recently approved the first PSMA-targeting ligands ⁶⁸Ga-PSMA-11 (Illuccix) and 18F-DCFPyL (Pylarify) for men with prostate cancer and suspected recurrence or metastases. Importantly, PSMA-PET has been shown to be not only more sensitive, but more specific than conventional imaging.2

Despite this great accuracy of PSMA-PET in localizing prostate cancer, the utility of PSMA-PET for measuring objective response to therapy is not fully elucidated. Response assessment is, however, of great relevance both for clinical trials and the clinical routine. Currently, the National Cancer Institute's response evaluation criteria in solid tumors (RECIST) 1.1 criteria are used for radiographic examinations and the PET evaluation response criteria in solid tumor (PERCIST) 1.0 are utilized for Fluorodeoxyglucose (FDG) PET examinations.7,8 However, for prostate cancer, the prostate cancer working group criteria 3 (PCWG3) guidelines still rely on bone scans and CT imaging and omit PSMA-PET to measure objective response.9

This is partly caused by the fact that clear guidelines for reporting and assessing response by PSMA-PET were lacking for a considerable period of time. The updated prostate cancer molecular imaging standardized evaluation (PROMISE) framework aims at providing guidelines both for the reporting of PSMA-PET examinations and for response assessment with exploratory templates which are compliant with existing response frameworks, but also provides a common basis for new ones.10 Already proposed response assessment frameworks are the PSMA-PET Progression (PPP) criteria and the Response Evaluation Criteria In PSMA-imaging (RECIP) 1.0, which are already gaining traction.11, 12, 13

In the upcoming years, PSMA-PET, due to its superior accuracy, will be included more and more in clinical studies on prostate cancer. Therefore, we urgently need a better understanding of the value of PSMA-PET for staging and response assessment. Here we report an overview of the current evidence and expert recommendations.