As LuPSMA enables selecting patients for treatment according to PSMA-PET/CT findings, its relatively high safety profile in previous trials, and the encouraging results in patients with metastatic disease support its examination in the neoadjuvant settings.2 Therefore, we investigated the safety and immediate oncological outcomes of patients with HRPCa who received two or three LuPSMA doses at two-week intervals, followed by robotic-assisted laparoscopic radical prostatectomy (RALP) with extended pelvic lymph nodes dissection.
The primary study endpoints were surgical complication rates and functional toxicity.
All patients who received LuPSMA were evaluable for toxicity, surgical complications, and changes in function and quality of life (QoL). We also evaluated the immediate oncological results regarding histological findings and the post-operative biochemical response rate.
Six and eight patients received two and three LuPSMA doses, respectively. None of the patients had grade ≥3 adverse events during the LuPSMA treatment period. No hematologic or endocrine disturbances were reported, and no patient discontinued treatment.
Of 14 patients who received LuPSMA, 13 underwent RALP with PLND with no intraoperative complications. ISUP group downgrading in 3 patients and upgrading in one patient. Overall, positive surgical margins (PSM) were observed in seven (53%) patients; four of them (30%) had more than minimal PSM (≥3 mm). Four patients had complications within 30 days after the operation. These included pneumonia (one patient, 8%), pulmonary embolism (PE; one patient, 8%), and urinary tract infection (UTI; 2 patients, 16%). No changes were found in urinary function, sexual function, or general QoL during the LuPSMA treatment period. Three months after the operation, 12 patients (92%) reported using ≤1 pad per day. Five weeks after surgery, 12 patients (92%) had undetectable PSA levels (<0.1 ng/ml).
The high safety profile of neoadjuvant treatment with LuPSMA followed by RALP could be explained by the localization and the relatively low total radiation dose of LuPSMA beta-particles when given to patients with PSMA-positive HRPCa.
The results of this study are limited mainly by the small number of patients. Nevertheless, we were able to show that RALP after neoadjuvant treatment with two or three LuPSMA doses is safe, thereby laying the foundation for larger trials.
Written by: Michael Frumer, MD, Department of Urology, Rabin Medical Center, Petah Tikva, Israel
Reference:
- Yong KJ, Milenic DE, Baidoo KE, Brechbiel MW (2016) Mechanisms of Cell Killing Response from Low Linear Energy Transfer (LET) Radiation Originating from (177)Lu Radioimmunotherapy Targeting Disseminated Intraperitoneal Tumor Xenografts. Int J Mol Sci 17
- Sartor O, de Bono J, Chi KN et al (2021) Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 385:1091-1103