Tobias Maurer1, Stephanie Robu2, Margret Schottelius2, Kristina Schwamborn3, Isabel Rauscher4, Nynke S van den Berg5, Fijs W B van Leeuwen6, Bernhard Haller7, Thomas Horn8, Matthias M Heck8, Jürgen E Gschwend8, Markus Schwaiger4, Hans-Jürgen Wester2, Matthias Eiber4. 1. Department of Urology, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany; Martini-Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: t.maurer@tum.de. 2. Pharmaceutical Radiochemistry, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany. 3. Institute of Pathology, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany. 4. Department of Nuclear Medicine, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany. 5. Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Otolaryngology, Head and Neck Surgery, School of Medicine, Stanford University, Stanford, CA, USA. 6. Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands. 7. Institute for Medical Statistics and Epidemiology, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany. 8. Department of Urology, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany.
Abstract
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).
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-PSMAN,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).
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