Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) has superior accuracy for detection of metastatic lesions in patients with prostate cancer (PC). Although PSMA PET has a prominent role in primary and secondary imaging of PC, data on its role in assessing treatment response in advanced PC are limited.
To review current data in the literature regarding the impact of antiandrogen therapy on PSMA expression of metastatic sites and the role of serial (baseline and at least 1 follow-up scan) PSMA PET to assess treatment response in patients with metastatic PC.
A comprehensive literature search in the PubMed database was performed using the terms “PSMA expression prostate”, “PSMA regulation”, “PSMA PET response assessment”, and “serial PSMA PET”.
Serial PSMA PET studies (baseline and at least 1 follow-up scan) provide valuable data regarding PSMA expression changes after systemic treatment in patients with metastatic PC. PSMA PET-detected flare and upregulation of PSMA expression following hormonal intervention seem to be early events resolving after 3 mo of treatment. PSMA PET imaging is essential in selecting patients for Lu-PSMA radioligand therapy (RLT). Growing evidence favors its use in assessing treatment responses after RLT. Preliminary evidence indicates the value of PSMA PET for assessment of the treatment response in patients receiving systemic treatment other than RLT for metastatic PC.
PSMA flare following antiandrogen therapy seems to be an early event and thus PET scans should be performed no earlier than 3 mo after the start of treatment. PSMA PET has a promising role in tailoring treatment according to the specific needs of individual patients and assessing responses following systemic treatment in patients with advanced PC.
This review describes how a sensitive imaging method can be used to assess the tumor response to treatment for metastatic prostate cancer.

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