^99mTechnetium-based Prostate-specific Membrane Antigen-radioguided Surgery in Recurrent Prostate Cancer

Background: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) can visualize metastatic lesions in recurrent prostate cancer (PC). However, reliable identification of small and/or atypically localized lesions during salvage surgery procedures is challenging.

Objective: To describe the technique, feasibility, and short-term outcomes of ^99mTechnetium (^99mTc)-based PSMA-radioguided surgery (^99mTc-PSMA-RGS) for removal of recurrent PC lesions.

Design, setting, and participants: Thirty-one consecutive patients with evidence of recurrent PC on ⁶⁸Ga-PSMA N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl] ethylenediamine-N,N'-diacetic acid (⁶⁸Ga-PSMA-11) PET after radical prostatectomy undergoing ^99mTc-PSMA-RGS were retrospectively analyzed.

Surgical procedure: Salvage surgery with intraoperative radioguidance using a gamma probe was performed after intravenous application of ^99mTc-PSMA investigation and surgery (mean activity 571 MBq, mean time to surgery 19.7h).

Measurements: Radioactive rating (positive vs negative) of resected tissue was compared with the findings of postoperative histopathological analysis. Best prostate-specific antigen (PSA) response without additional treatment was determined after 8-16 wk postoperatively. Biochemical recurrence- and treatment-free survival was evaluated.

Results and limitations: In total, 132 tissue specimens were removed, of which 58 showed metastatic involvement on histological analysis. On a specimen basis, radioactive rating yielded a sensitivity of 83.6% (confidence interval [CI]: 70.9-91.5%), a specificity of 100%, and an accuracy of 93.0% (CI: 85.5-96.7%). With ^99mTc-PSMA-RGS, all lesions visualized on preoperative ⁶⁸Ga-PSMA-11 PET could be removed. Moreover, ^99mTc-PSMA-RGS detected additional metastases as small as 3mm in two patients. Thirteen patients suffered from complications related to surgery (Clavien-Dindo grade 1: 12 patients; grade 3a: one patient). A PSA reduction below 0.2 ng/ml was observed in 20 patients. Thirteen patients remained biochemical recurrence free after a median follow-up of 13.8 (range: 4.6-18.3) mo. Twenty patients continued to be treatment free after a median follow-up of 12.2 (range: 5.5-18.3) mo.

Conclusions: As a new technique for surgical guidance, ^99mTc-PSMA-RGS is feasible, and has been proved to be of high value for successful intraoperative detection and removal of metastatic lesions in PC patients scheduled for salvage surgery. Its long-term impact on outcome has to be evaluated.

Patient summary: In this report, we evaluated a novel technique to identify metastatic lesions intraoperatively in patients with recurrent prostate cancer to facilitate surgical removal. After intravenous injection of radioactive molecules that specifically bind to prostate cancer cells that show increased expression of the prostate-specific membrane antigen, we were able to detect and remove these metastatic lesions during surgery. Following salvage surgery, 41.9% of patients remained biochemical recurrence free (median follow-up of 13.8 mo) and 64.5% continued to be treatment free (median follow-up of 12.2 mo).