Current treatment of N1M0 prostate cancer (PCa) with locoregional external beam radiotherapy (EBRT) and long-term androgen deprivation therapy (ADT) has suboptimal five-year recurrence-free rates. Adding [177Lu]Lu-PSMA-617 may improve tumour control and reduce reliance on long-term ADT. This phase-1 dose-escalation study explores the safety and tolerability of adding concurrent [177Lu]Lu-PSMA-617 with EBRT and ADT.
In the multi-centre phase-1 dose-escalation study (PROQURE-I), treatment-naïve cT1-4N1M0 PCa patients received standard locoregional EBRT (25-35 fractions) and 2-3 years ADT with concurrent [177Lu]Lu-PSMA-617 to determine its maximum tolerated dose (MTD). Dose levels included one cycle (3, 6 or 9 GBq in week 2 of EBRT) or two cycles (2 × 7.4 GBq in week 2 and 4). Grade ≥ 3 toxicity (CTCAE v5.0) was dose-limiting. Tumour and organ dosimetry was performed with SPECT/CT and planar imaging at 4, 24 and 168 h post-injection.
Fourteen patients were included. No dose-limiting toxicity was observed and the MTD was not reached. Reported grade 1-2 toxicities were related to EBRT. Median absorbed dose to the primary tumour of 0.71 Gy/GBq (interquartile range (IQR) 0.5-2.9) at the 9 GBq; 0.91 Gy/GBq (IQR 0.6-1.0) at 7.4 GBq cycle 1; and 0.47 Gy/GBq (0.3-0.5) at cycle 2.
Concurrent [177Lu]Lu-PSMA-617 with EBRT and ADT is safe and well tolerated in treatment-naïve N1M0 PCa. Clinical efficacy should be evaluated in a subsequent phase 2 study.
European journal of nuclear medicine and molecular imaging. 2026 May 27 [Epub ahead of print]
Lotte G Zuur, Denise S Hoogenkamp, Esmée C A van der Sar, Debra van Asten, Marnix G E H Lam, Jochem R N van der Voort-van Zyp, Pim J van Leeuwen, Berlinda J de Wit-van der Veen, Daphne M V de Vries-Huizing, Jeroen J M A Hendrikx, Arthur J A T Braat, Wouter V Vogel
Department of Urology, Netherlands Cancer Institute, Amsterdam, the Netherlands., Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam, the Netherlands., Department of Radiology and Nuclear Medicine, University Medical Centre Utrecht, Utrecht, the Netherlands., Department of Radiation Oncology, University Medical Centre Utrecht, Utrecht, the Netherlands., Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam, the Netherlands. .