Neoadjuvant Lu-PSMA-I&T Radionuclide Treatment in Patients with High-risk Prostate Cancer Before Radical Prostatectomy: A Single-arm Phase 1 Trial.

Background: High-risk localized prostate cancer (HRLPC) has a substantial risk of disease progression despite local treatment. Neoadjuvant systemic therapy before definitive local therapy may improve oncological outcomes by targeting the primary tumor and micrometastatic disease.

Objective: To evaluate whether a lutetium-177 prostate-specific membrane antigen radioligand (LuPSMA) can be safely administered to patients with HRLPC before robot-assisted radical prostatectomy (RARP) and to describe immediate oncological outcomes.

Design, Setting, And Participants: This was an open-label, single-arm clinical trial. Patients with HRLPC and elevated radioligand uptake on PSMA positron emission tomography/computed tomography were enrolled. Two or three LuPSMA radioligand doses (7.4 GBq) were given at 2-wk intervals. RARP with lymph node dissection was performed 4 wk after the last LuPSMA dose.

Outcome Measurements And Statistical Analysis: The rate of surgical complications, operative parameters, changes in functional and quality-of-life measures, and immediate oncological outcomes (histological findings and biochemical response) were measured. Data were analyzed descriptively.

Results And Limitations: Fourteen patients participated (median age 67 yr). Prostate-specific antigen decreased by 17% (interquartile range [IQR] 9-50%) after two LuPSMA doses and 34% (IQR 11-60%) after three doses. Thirteen patients underwent RARP with no identifiable anatomical changes or intraoperative complications. Four patients (30%) had postoperative complications (pneumonia, pulmonary embolism, urinary leak with urinary tract infection). At 3 mo postoperatively, 12 patients (92%) required one pad or less. Final whole-mount pathology showed positive surgical margins (PSMs) in seven patients (53%) and downgrading to International Society of Urological Pathology grade group 3 in three patients (23%). Treatment-related effects included a clear vacuolated cytoplasm and pyknotic nuclei.

Conclusions: LuPSMA followed by RARP appears to be surgically safe. While oncological outcomes are pending, continence recovery seems to be unaffected by LuPSMA treatment.

Patient Summary: We evaluated outcomes for patients with aggressive localized prostate cancer who received treatment with a radioactive agent before surgical removal of their prostate. This approach appears to be safe and feasible, but its therapeutic efficacy is still unknown.