PSMA-PET as an emerging tool for response assessment in metastatic prostate cancer (mPC): Revolution and necessary evolution.

This article critically reviews the available evidence on the role of PSMA-PET in evaluating therapeutic response in metastatic prostate cancer (mPC), comparing it with conventional criteria -serum PSA levels, Response Evaluation Criteria in Solid Tumours (RECIST 1.1), Prostate Cancer Working Group 3 (PCWG3)- and analyzing its integration into clinical practice. It addresses the biological basis of PSMA and how different treatments -androgen deprivation therapy (ADT), androgen receptor pathway inhibitors (ARPI), taxanes, [¹⁷⁷Lu]Lu-PSMA-617, [²²³Ra], stereotactic body radiotherapy (SBRT)- modulate its expression, which influences image interpretation and phenomena such as flare. This work describes specific assessment systems for PSMA-PET, including PSMA PET Progression Criteria (PPP), Response Evaluation Criteria in PSMA (RECIP 1.0), and EAU/EANM criteria, highlighting their superior prognostic value compared to RECIST and PCWG3, especially in metastatic castration-resistant prostate cancer (mCRPC). RECIP 1.0, initially validated for [¹⁷⁷Lu]Lu-PSMA-617, has demonstrated robust correlation with overall survival and interobserver reproducibility, improving risk stratification when combined with PSA. Quantitative parameters such as PSMA-VOL and TLP, key biomarkers for monitoring response and predicting outcomes, are analyzed. Furthermore, the evidence is reviewed by therapeutic modality, proposing practical recommendations on the optimal timing for PSMA-PET (baseline, intermediate, or delayed depending on treatment) and the need for standardized reporting (PROMISE, E-PSMA). The article also identifies current limitations: variability among radiopharmaceuticals, a lack of universal criteria, a scarcity of prospective studies, and challenges in multimodal integration with PSA and other biomarkers.