High-risk localised prostate cancer (HRCaP) has high rates of biochemical recurrence; [177Lu]Lu-PSMA-617 is effective in men with advanced prostate cancer.
To investigate the dosimetry, safety, and efficacy of upfront [177Lu]Lu-PSMA-617 in men with HRCaP prior to robotic radical prostatectomy (RP).
In this single-arm, phase I/II trial, we recruited men with HRCaP (any of prostate-specific antigen [PSA] >20 ng/ml, International Society of Urological Pathology (ISUP) grade group [GG] 3-5, and ≥cT2c), with high tumour uptake on [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PSMA PET/CT), and scheduled for RP.
Cohort A (n = 10) received one cycle and cohort B (n = 10) received two cycles of [177Lu]Lu-PSMA-617 (5 GBq) followed by surgery 6 weeks later.
The primary endpoint was tumour radiation absorbed dose. Adverse events (AEs; Common Terminology Criteria for Adverse Events (CTCAE) version 5.0), surgical safety (Clavien-Dindo), imaging, and biochemical responses were evaluated (ClinicalTrials.gov: NCT04430192).
Between May 29, 2020 and April 28, 2022, 20 patients were enrolled. The median PSA was 18 ng/ml (interquartile range [IQR] 11-35), Eighteen (90%) had GG ≥3, and six (30%) had N1 disease. The median (IQR) highest tumour radiation absorbed dose after cycle 1 for all lesions was 35.5 Gy (19.5-50.1), with 19.6 Gy (11.3-48.4) delivered to the prostate. Five patients received radiation to lymph nodes. Nine (45%) patients achieved >50% PSA decline. The most common AEs related to [177Lu]Lu-PSMA-617 were grade 1 fatigue in eight (40%), nausea in seven (35%), dry mouth in six (30%), and thrombocytopenia in four (20%) patients. No grade 3/4 toxicities or Clavien 3-5 complications occurred. Limitations include small a sample size.
In men with HRCaP and high prostate-specific membrane antigen (PSMA) expression, [177Lu]Lu-PSMA-617 delivered high levels of targeted radiation doses with few toxicities and without compromising surgical safety. Further studies of [177Lu]Lu-PSMA-617 in this population are worthwhile to determine whether meaningful long-term oncological benefits can be demonstrated.
In this study, we demonstrate that up to two cycles of [177Lu]Lu-PSMA-617 given prior to radical prostatectomy in patients with high-risk localised prostate cancer are safe and deliver targeted doses of radiation to tumour-affected tissues. It is tolerated well with minimal treatment-related adverse events, and surgery is safe with a low rate of complications. Activity measured through PSA reduction, repeat PSMA PET/CT, and histological response is promising.
European urology. 2023 Oct 25 [Epub ahead of print]
Renu S Eapen, James P Buteau, Price Jackson, Catherine Mitchell, Sheng F Oon, Omar Alghazo, Lachlan McIntosh, Nattakorn Dhiantravan, Mark J Scalzo, Jonathan O'Brien, Shahneen Sandhu, Arun A Azad, Scott G Williams, Gaurav Sharma, Mohammad B Haskali, Mathias Bressel, Kenneth Chen, Pocharapong Jenjitranant, Aoife McVey, Daniel Moon, Nathan Lawrentschuk, Paul J Neeson, Declan G Murphy, Michael S Hofman
Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia; Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia. Electronic address: ., Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia., Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, Australia., Department of Anatomical Pathology, Peter MacCallum Cancer Centre, Melbourne, Australia., Department of Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia., Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia., Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia., Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC), Peter MacCallum Cancer Centre, Melbourne, Australia; Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia., Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia., Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia., Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC), Peter MacCallum Cancer Centre, Melbourne, Australia., Radiopharmaceutical Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia., Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Australia., Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia; Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC), Peter MacCallum Cancer Centre, Melbourne, Australia., Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia., Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia; Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.