Eapen Renu S, Buteau James P, Jackson Price, Mitchell Catherine, Oon Sheng F, Alghazo Omar, McIntosh Lachlan, Dhiantravan Nattakorn, Scalzo Mark J, O'Brien Jonathan, Sandhu Shahneen, Azad Arun A, Williams Scott G, Sharma Gaurav, Haskali Mohammad B, Bressel Mathias, Chen Kenneth, Jenjitranant Pocharapong, McVey Aoife, Moon Daniel, Lawrentschuk Nathan, Neeson Paul J, Murphy Declan G, Hofman Michael S
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.
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.
Eur Urol. 2024 Mar;85(3):217-226. doi: 10.1016/j.eururo.2023.08.026. Epub 2023 Oct 26.
High-risk localised prostate cancer (HRCaP) has high rates of biochemical recurrence; [Lu]Lu-PSMA-617 is effective in men with advanced prostate cancer.
To investigate the dosimetry, safety, and efficacy of upfront [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 [Ga]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 [Lu]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 [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.
In men with HRCaP and high prostate-specific membrane antigen (PSMA) expression, [Lu]Lu-PSMA-617 delivered high levels of targeted radiation doses with few toxicities and without compromising surgical safety. Further studies of [Lu]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 [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.
高危局限性前列腺癌（HRCaP）的生化复发率很高；[镥]镥 - PSMA - 617对晚期前列腺癌男性患者有效。
研究在机器人根治性前列腺切除术（RP）前，对HRCaP男性患者进行 upfront [镥]镥 - PSMA - 617治疗的剂量测定、安全性和疗效。
设计、设置和参与者：在这项单臂I/II期试验中，我们招募了HRCaP患者（前列腺特异性抗原[PSA]＞20 ng/ml、国际泌尿病理学会（ISUP）分级组[GG] 3 - 5且≥cT2c中的任何一项），这些患者在[镓]镓 - PSMA - 11正电子发射断层扫描/计算机断层扫描（PSMA PET/CT）上有高肿瘤摄取，且计划进行RP。
A组（n = 10）接受一个周期，B组（n = 10）接受两个周期的[镥]镥 - PSMA - 617（5 GBq），6周后进行手术。
主要终点是肿瘤辐射吸收剂量。评估不良事件（AE；不良事件通用术语标准（CTCAE）第5.0版）、手术安全性（Clavien-Dindo）、影像学和生化反应（ClinicalTrials.gov：NCT04430192）。
在2020年5月29日至2022年4月28日期间，招募了20名患者。PSA中位数为18 ng/ml（四分位间距[IQR] 11 - 35），18名（90%）患者GG≥3，6名（30%）患者有N1疾病。所有病灶在第1周期后的最高肿瘤辐射吸收剂量中位数（IQR）为35.5 Gy（19.5 - 50.1），前列腺接受的剂量为19.6 Gy（11.3 - 48.4）。5名患者接受了淋巴结放疗。9名（45%）患者PSA下降＞50%。与[镥]镥 - PSMA - 617相关的最常见AE为8名（40%）患者出现1级疲劳、7名（35%）患者出现恶心、6名（30%）患者出现口干、4名（20%）患者出现血小板减少。未发生3/4级毒性反应或Clavien 3 - 5级并发症。局限性包括样本量小。
在HRCaP且前列腺特异性膜抗原（PSMA）高表达的男性患者中，[镥]镥 - PSMA - 617能提供高水平的靶向辐射剂量，毒性小且不影响手术安全性。对该人群进一步研究[镥]镥 - PSMA - 617是否能带来有意义的长期肿瘤学获益是值得的。
在本研究中，我们证明在高危局限性前列腺癌患者根治性前列腺切除术之前给予多达两个周期的[镥]镥 - PSMA - 617是安全的，并且能向受肿瘤影响的组织输送靶向辐射剂量。它耐受性良好，治疗相关不良事件极少，手术安全，并发症发生率低。通过PSA降低、重复PSMA PET/CT和组织学反应所测量的活性很有前景。
