Administering [ 177 Lu]Lu-PSMA-617 Prior to Radical Prostatectomy in Men with High-risk Localised Prostate Cancer (LuTectomy): A Single-centre, Single-arm, Phase 1/2 Study.

Autor: Eapen RS; 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: Renu.Eapen@petermac.org., Buteau JP; 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., Jackson P; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, Australia., Mitchell C; Department of Anatomical Pathology, Peter MacCallum Cancer Centre, Melbourne, Australia., Oon SF; Department of Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia., Alghazo O; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia., McIntosh L; Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia., Dhiantravan N; Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia., Scalzo MJ; 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., O'Brien J; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia., Sandhu S; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia., Azad AA; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia., Williams SG; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia., Sharma G; Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC), Peter MacCallum Cancer Centre, Melbourne, Australia., Haskali MB; Radiopharmaceutical Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia., Bressel M; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Australia., Chen K; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia., Jenjitranant P; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia., McVey A; 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., Moon D; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia., Lawrentschuk N; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia., Neeson PJ; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia., Murphy DG; 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., Hofman MS; 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.
Jazyk: angličtina
Zdroj: European urology [Eur Urol] 2024 Mar; Vol. 85 (3), pp. 217-226. Date of Electronic Publication: 2023 Oct 26.
DOI: 10.1016/j.eururo.2023.08.026
Abstrakt: Background: High-risk localised prostate cancer (HRCaP) has high rates of biochemical recurrence; [ 177 Lu]Lu-PSMA-617 is effective in men with advanced prostate cancer.
Objective: To investigate the dosimetry, safety, and efficacy of upfront [ 177 Lu]Lu-PSMA-617 in men with HRCaP prior to robotic radical prostatectomy (RP).
Design, Setting, and Participants: 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 [ 68 Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PSMA PET/CT), and scheduled for RP.
Intervention: Cohort A (n = 10) received one cycle and cohort B (n = 10) received two cycles of [ 177 Lu]Lu-PSMA-617 (5 GBq) followed by surgery 6 weeks later.
Outcome Measurements and Statistical Analysis: 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).
Results and Limitations: 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 [ 177 Lu]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.
Conclusions: In men with HRCaP and high prostate-specific membrane antigen (PSMA) expression, [ 177 Lu]Lu-PSMA-617 delivered high levels of targeted radiation doses with few toxicities and without compromising surgical safety. Further studies of [ 177 Lu]Lu-PSMA-617 in this population are worthwhile to determine whether meaningful long-term oncological benefits can be demonstrated.
Patient Summary: In this study, we demonstrate that up to two cycles of [ 177 Lu]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.
(Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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