177Lu-PSMA therapy in metastatic prostate cancer: An updated review of prognostic and predictive biomarkers

Highlights•177Lu-PSMA is a new option in PSMA-positive metastatic castration-resistant (mCRPC) patients.•A high proportion of patients do not respond 177Lu-PSMA.•Prognostic and predictive biomarkers for 177Lu-PSMA are under investigation.•The identification of biomarkers is essential for optimizing the use of 177Lu-PSMA in this setting.Abstract177Lu-PSMA has been approved for the treatment of PSMA-positive metastatic castration-resistant (mCRPC) patients who progressed to androgen receptor pathway inhibitors (ARPIs) and taxane-based chemotherapy. However, a higher proportion of patients do not respond to this type of radioligand therapy (RLT). To date, there is a lack of validated prognostic and predictive biomarkers for 177Lu-PSMA therapy in prostate cancer. Several studies have investigated the prognostic and predictive role of clinical and molecular factors and also the metabolic features of PET imaging. In this review, we aim to take stock of the current scenario, focusing on new emerging data from retrospective/prospective series and clinical trials. Given the high costs and the possibility of primary resistance, it seems essential to identify clinical and molecular characteristics that could allow clinicians to choose the right patient to treat with 177Lu-PSMA. Biomarker-based clinical trials are urgently needed in this field.