Administering [177Lu]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

Eapen, RS; Buteau, JP; Jackson, P; Mitchell, C; Oon, SF; Alghazo, O; McIntosh, L; Dhiantravan, N; Scalzo, MJ; O&#39;Brien, J; Sandhu, S; Azad, AA; Williams, SG; Sharma, G; Haskali, MB; Bressel, M; Chen, K; Jenjitranant, P; McVey, A; Moon, D; Lawrentschuk, N; Neeson, PJ; Murphy, DG; Hofman, MS

Author(s): Eapen, RS; Buteau, JP; Jackson, P; Mitchell, C; Oon, SF; Alghazo, O; McIntosh, L; Dhiantravan, N; Scalzo, MJ; O'Brien, J; Sandhu, S; Azad, AA; Williams, SG; Sharma, G; Haskali, MB; Bressel, M; Chen, K; Jenjitranant, P; McVey, A; Moon, D; Lawrentschuk, N; Neeson, PJ; Murphy, DG; Hofman, MS;
Details: Publication Year 2024-03,Volume 85,Issue #3,Page 217-226
Journal Title: European Urology
Publication Type: Research article
Abstract: 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.
Publisher: Elsevier
Keywords: Male; Humans; Prostate-Specific Antigen; Prostate/pathology; Positron Emission Tomography Computed Tomography/methods; Gallium Radioisotopes; *Prostatic Neoplasms/surgery/pathology; Prostatectomy/methods; *Prostatic Neoplasms, Castration-Resistant/pathology; Lutetium/adverse effects; Treatment Outcome; *Dipeptides; *Heterocyclic Compounds, 1-Ring; Lutetium PSMA; Neoadjuvant; Prostate cancer; Radical prostatectomy; Theranostics
Department(s): Surgical Oncology; Cancer Imaging; Physical Sciences; Pathology; Medical Oncology; Radiation Oncology; Biostatistics and Clinical Trials; Laboratory Research
Publisher's Version: https://doi.org/10.1016/j.eururo.2023.08.026
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-04-02 04:13:36

Last Modified: 2024-04-02 04:13:52