Background
In metastatic castration-resistant prostate cancer (mCRPC), using serum prostate-specific antigen (PSA) levels to evaluate treatment response is not always accurate. This study aimed to assess the efficacy of PSMA PET/CT at specific time points for evaluating treatment response and predicting survival in mCRPC patients, compared to PSA.

Methods
Sixty mCRPC patients underwent [18F]PSMA-1007 PET/CT at baseline and for treatment response evaluation of either androgen receptor-targeted agents (after 3 months) or chemotherapy (after completion), and were retrospectively analysed. Visual assessment categorised overall response and response of the worst responding lesion as partial response, stable disease, or progressive disease, using the EAU/EANM criteria. Additionally, percentage changes in SUVmax, total tumour volume and total lesion uptake (tumour volume * SUVmean) were calculated. PSA response was defined according to the PCWG3 criteria. Cox regression analysis identified predictors of overall survival.

Results
PSMA PET/CT and PSA response were discordant in 47 % of patients, and PSMA PET/CT response was worse in 89 % of these cases. Overall response on PSMA PET/CT independently predicted overall survival (progression versus non-progression: HR = 4.05, p < 0.001), outperforming PSA response (progression versus non-progression: HR = 2.53, p = 0.010) and other PSMA PET/CT parameters. Among patients with a PSA decline of > 50 %, 31 % showed progressive disease on PSMA PET/CT, correlating with higher mortality risk (progression versus non-progression: HR = 4.38, p = 0.008). No flare in PSMA uptake was observed in this cohort.

Conclusions
PSMA PET/CT for assessing treatment response at predefined time points was superior to PSA-based response for predicting overall survival in mCRPC patients treated with androgen receptor-targeted agents and chemotherapy. PSMA PET/CT showed the ability to detect disease progression earlier than PSA levels, which can affect treatment decisions and has the potential to improve patient outcomes. We recommend further research to validate these findings in larger patient cohorts, to extend the number of treatments, and to evaluate cost-effectiveness and impact on patient outcomes.