Clinical Responses to Prostate-specific Membrane Antigen Radioguided Salvage Lymphadenectomy for Prostate Cancer Recurrence: Results from a Prospective Exploratory Trial

Background and objective: Prostate-specific membrane antigen (PSMA) radioguided salvage pelvic lymph node dissection (S-PLND) has emerged as a feasible treatment option for prostate cancer recurrence following initial surgery. This study aims to evaluate the feasibility and short-term outcomes of PSMA radioguided S-PLND.

Methods: From a prospective trial of ^99mTc-PSMA-I&S followed by PSMA radioguided robotic surgery, we evaluated patients treated for node-only recurrence following radical therapy. The primary outcome was serum prostate-specific antigen (PSA) response 3 mo after surgery.

Key findings and limitations: Among 14 patients (enrolled from June 2021 to June 2023), the median age was 65 yr. One patient had undergone primary whole gland ultrasound ablation, while the rest received prior prostatectomy. The median (interquartile range) time from primary treatment to PSMA positron emission tomography (PET) was 4.1 (2.9-8.3) yr, and 21 total pelvic targets were noted on PSMA PET: one in eight patients (67%), two in five patients (29%), and three in one patient (7%). Targets were successfully detected intraoperatively and removed in 13/14 (93%) patients. Cancer was noted on histopathology in 90% (19/21) of PSMA PET targets, 94% (17/18) of single-photon emission computed tomography targets, and 82% (14/17) of gamma probe targets. There were no adverse effects due to the radiotracer, and there were no complications after surgery. PSA at 3 mo was <0.2 ng/ml in two (14%) patients, and a ≥50% decline was noted in five (36%) patients. After a mean follow-up of 8.3 mo, the median time to next treatment was 11.7 mo, which was noted in nine patients.

Conclusions and clinical implications: PSMA radioguided S-PLND is feasible and safe. However, the clinical role and the honing of technique and patient selection will be required in prospective studies.

Patient summary: In 14 patients who had prostate cancer recurrence after their initial treatment, performing surgery using radioactive tags to location is possible. However, futures studies are still needed to improve the technique.