The use of prostate-specific membrane antigen (PSMA)-directed applications in modern prostate cancer management has evolved rapidly over the past few years, helping to establish new treatment pathways and provide further insights into prostate cancer biology. However, the prognostic implications of PSMA-PET have not been studied systematically, owing to rapid clinical implementation without long follow-up periods to determine intermediate-term and long-term oncological outcomes. Currently available data suggest that traditional prognostic factors and survival outcomes are associated with high PSMA expression (both according to immunohistochemistry and PET uptake) in men with localized and biochemically recurrent disease. Treatment with curative intent (primary and/or salvage) often fails when PSMA-positive metastases are present; however, the sensitivity of PSMA-PET in detecting all metastases is poor. Low PSMA-PET uptake in recurrent disease is a favourable prognostic factor; however, it can be associated with poor prognosis in conjunction with high 18F-fluorodeoxyglucose uptake in metastatic castration-resistant prostate cancer. Clinical trials embedding PSMA-PET for guiding management with reliable oncological outcomes are needed to support ongoing clinical use.
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