These cohorts confirmed that [177Lu]Lu-PSMA-617 could achieve meaningful clinical and survival benefit outside clinical trials, including in older and heavily pre-treated patients. Among heterogeneous populations, PSA response rates and overall survival outcomes remained broadly consistent with prospective studies, while maintaining an acceptable safety profile in routine practice.
Importantly, EAPs also helped refine patient selection. Real-world experience demonstrated that not all PSMA-positive patients benefited equally from therapy. Low PSMA expression, discordant FDG-positive/PSMA-negative disease, and extensive liver metastases emerged as markers of poorer outcomes. In parallel, high skeletal tumour burden appeared as a predictor of increased haematological toxicity and treatment-related challenges. Indeed, the current understanding of “who truly benefits from PSMA-RLT” is shaped as much by these real-world observations as by prospective trials themselves.
These programs also provided more individualized treatment approaches. Beyond the constraints of clinical trials, selected patients underwent retreatment or extended treatment courses according to molecular imaging findings, treatment tolerance, and residual tumour burden. Compassionate use cohorts similarly contributed to the emergence of alpha-particle therapy, with [225Ac]Ac-PSMA-617 demonstrating remarkable anti-tumour activity in heavily pre-treated patients relapsing after [177Lu]Lu-PSMA.
Molecular imaging also progressively expanded beyond patient selection alone. In many patients, PSMA PET provided a more comprehensive evaluation of disease heterogeneity and therapeutic assessment than PSA kinetics alone, contributing to the development of imaging-based response frameworks such as RECIP 1.0. Increasingly, PSMA PET became integrated into prognostic evaluation, response assessment, toxicity anticipation, and longitudinal therapeutic decision-making.
Ultimately, EAPs did more than bridge the gap before regulatory approval. They helped define how PSMA-RLT is now practiced in clinical practice: as a multidisciplinary and increasingly adaptive therapeutic strategy integrating molecular imaging.
Written by: Chloe François and Clement Bailly
- Nuclear Medicine Department, Nantes University Hospital, Nantes, France; Nantes Université, Inserm, CNRS, Université d'Angers, CRCI2NA, Nantes, France