Predictive value of early PSMA upregulation for the response to enzalutamide ± 177 Lu-PSMA-617 in poor-risk, metastatic, castration-resistant prostate cancer: substudy of the randomized, phase 2 ENZA-p trial

A substudy of the randomized phase 2 ENZA-p trial, published in Nature Cancer, evaluated the frequency, magnitude, and clinical significance of early prostate-specific membrane antigen (PSMA) upregulation in patients with poor-risk metastatic castration-resistant prostate cancer treated with enzalutamide alone or combined with the radioligand therapy 177Lu-PSMA-617. The findings by Emmett and colleagues shed light on whether early changes in PSMA expression on imaging can predict which patients will benefit most from the addition of lutetium-PSMA therapy. This biomarker-driven approach is important because it could help clinicians personalize treatment decisions in a disease setting with limited options and poor prognosis. The ENZA-p trial is among the first to prospectively combine androgen receptor pathway inhibitors with PSMA-targeted radioligand therapy, making its translational substudies particularly relevant to the rapidly evolving theranostics field.