Neoadjuvant 177Lu-PSMA-I&T Radionuclide Treatment in Patients with High-risk Prostate Cancer Before Radical Prostatectomy: A Single-arm Phase 1 Trial.

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.

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.

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.

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.

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.

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

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.

European urology oncology. 2022 Oct 07 [Epub ahead of print]

Shay Golan, Michael Frumer, Yarden Zohar, Eli Rosenbaum, Maxim Yakimov, Daniel Kedar, David Margel, Jack Baniel, Adam P Steinmetz, David Groshar, Liran Domachevsky, Hanna Bernstine

Department of Urology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: ., Department of Urology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Department of Urology, Rabin Medical Center, Petah Tikva, Israel., Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Oncology, Rabin Medical Center, Petah Tikva, Israel., Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Pathology, Rabin Medical Center, Petah Tikva, Israel., Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Nuclear Medicine, Rabin Medical Center, Petah Tikva, Israel., Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Nuclear Medicine, Chaim Sheba Medical Center, Ramat Gan, Israel.

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