PSMA PET/CT Kinetics During Systemic Therapy and Radiotherapy in Hormone-sensitive Prostate Cancer: A Systematic Review

Context Although prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is commonly used for both initial staging and restaging at biochemical recurrence for patients diagnosed with prostate cancer (PCa), its role in the evaluation of treatment response is currently not validated. Objectives We aimed to identify studies that implemented PSMA PET/CT as a restaging modality for patients with hormone-sensitive PCa (HSPC) and highlight the evolution of PSMA PET/CT parameters to assess its potential use for treatment response evaluation. Evidence Acquisition A systematic review was performed using the MEDLINE, Scopus, and Embase databases until December 2025. Studies deemed eligible were those reporting PSMA expression dynamics under either systemic therapy or after radiotherapy (RT). Evidence synthesis A total of 11 studies were included, including two prospective single-arm studies and nine retrospective studies. Under androgen deprivation therapy (ADT), a decrease in PSMA expression was observed across all disease sites. In one prospective study, a flare phenomenon (increase ≥20% in tracer uptake) was observed at the lesion level in 26% of bone lesions and 11% of nodal and prostate lesions at 3–4 wk, with a median change in maximum standardized uptake value (ΔSUVmax) of +50% (interquartile range 32–72) in bone lesions showing flare. At 22 wk, one retrospective study reported mean SUVmax reductions of 48%, 59%, and 74% in prostate, nodal, and bone lesions, respectively. Other studies at different time points each reported reductions in prostate SUVmax ranging from 49% to 67%, with differences in whether estimates were summarized as means or medians. After RT, one retrospective study suggested that the reduction in prostate SUVmax may be more pronounced in patients receiving concomitant ADT (mean reduction –59% ± 25% vs –45% ± 31% for RT alone; p = 0.004). Conclusions PSMA PET-derived parameters hold the potential to personalize treatment strategies depending on treatment response. The relationship between changes in PSMA expression and oncological outcomes warrants further investigation in other studies.