A key unanswered question in prostate-specific membrane-antigen (PSMA) targeted radioligand therapy is whether we have chosen therapy doses and regimens that are "safe" rather than "effective," with phase 3 trials to date guided by conservative external beam derived dose constraints. However, is increasing administered dose or short interval fractionated dose safe, and does it even make a difference to patient outcomes? The goal of the OPTIMAL-PSMA trial is to determine the depth of response and safety of intense-induction then maintenance dosing compared to standard-of-care six doses 6-weekly [177Lu] Lu-PSMA-597 in men with metastatic castration-resistant prostate cancer (mCRPC). This mini review will evaluate the scientific evidence and rationale for dose intensification with PSMA-targeted radioligand therapy (PSMA-RLT). It will cover existing trials that are evaluating a variety of dose-dense regimens and give a more in-depth overview of the OPTIMAL-PSMA trial.
European urology focus. 2026 Jul 23 [Epub ahead of print]
Gemma Sheehan-Dare, Sobia Khan, Louise Emmett
Theranostics and Nuclear Medicine, St Vincent's Hospital, Sydney, Australia., Theranostics and Nuclear Medicine, St Vincent's Hospital, Sydney, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, Australia. Electronic address: .