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State of the Art in Prostate-specific Membrane Antigen-targeted Surgery-A Systematic Review
Anne-Claire Berrens1,2, Sophie Knipper3,4, Giancarlo Marra5
1Department of Urology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Context:
Identifying malignant tissue and leaving adjacent structures undisturbed constitute an ongoing challenge in prostate cancer (PCa) surgery. Image and radioguided surgical technologies targeting the prostate-specific membrane antigen (PSMA) receptor may facilitate identification and removal of diseased tissue.
Objective:
To perform a systematic review of the clinical studies on PSMA-targeted surgery.
Evidence Acquisition:
The MEDLINE (OvidSP), Embase.com, and Cochrane Library databases were searched. Identified reports were critically appraised according to the Idea, Development, Exploration, Assessment, Long-term framework criteria. The risk of bias (RoB) was assessed as per the Risk Of Bias In Non-randomized Studies-of Interventions tool. The strengths and limitations of the techniques and corresponding oncological outcomes were extracted as areas of interest. Data were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.
Evidence Synthesis:
In total, 29 reports were selected, including eight prospective studies, 12 retrospective analyses, and nine case reports, all with a high or an unclear RoB. In 72.4% of studies, PSMA targeting was achieved via radioguided surgery (RGS), predominantly using 99mTc-PSMA-I&S (66.7%). Hybrid approaches that complement RGS with optical guidance are emerging. The majority of studies retrieved were pilot studies with a short follow-up. In 13 reports, salvage lymph node surgery was discussed (44.8%). In 12 more recent reports (41.4%), PSMA targeting was studied in primary PCa surgery (50.0% lymph nodes and 50.0% surgical margins), and four studied both primary and salvage surgery (13.8%). Overall, specificity was higher than sensitivity (median 98.9% and 84.8%, respectively). Oncological outcomes were discussed only in reports on the use of 99mTc-PSMA-I&S in salvage surgery (median follow-up of 17.2 mo). A decline in prostate-specific antigen level of >90% ranged from 22.0% to 100.0%, and biochemical recurrence ranged from 50.0% to 61.8% of patients.
Conclusions:
In PSMA-targeted surgery, most studies address salvage PSMA-RGS using 99mTc-PSMA-I&S. Available evidence suggests that the specificity of intraoperative PSMA targeting is higher than the sensitivity. The studies that included follow-up did not yet objectify a clear oncological benefit. Lacking solid outcome data, PSMA-targeted surgery remains investigational.
Patient Summary:
In this paper, we review recent advances in prostate-specific membrane antigen (PSMA)-targeted surgery, which is used to help identify and remove prostate cancer. We found good evidence to suggest that PSMA targeting helps identify prostate cancer during surgery. The oncological benefits have yet to be investigated further.
Insights
Prostate cancer surgery benefits from PSMA-targeted techniques for identifying malignant tissue. However, current evidence suggests higher specificity than sensitivity, and oncological benefits require further investigation.
Area of Science:
- Urology
- Oncology
- Surgical Technology
Background:
- Prostate cancer (PCa) surgery faces challenges in precisely identifying malignant tissue while preserving adjacent structures.
- Prostate-specific membrane antigen (PSMA) receptor-targeted imaging and radioguided surgical technologies offer potential solutions for improved diseased tissue localization and removal.
Purpose of the Study:
- To systematically review clinical studies evaluating PSMA-targeted surgery for prostate cancer.
- To assess the strengths, limitations, and oncological outcomes of PSMA-targeted surgical techniques.
Main Methods:
- A systematic literature search was conducted across MEDLINE, Embase.com, and Cochrane Library.
- Included reports were critically appraised using the Idea, Development, Exploration, Assessment, Long-term framework and Risk Of Bias In Non-randomized Studies-of Interventions tool.
- Data on techniques, strengths, limitations, and oncological outcomes were extracted following PRISMA guidelines.
Main Results:
- Twenty-nine reports were selected, predominantly focusing on radioguided surgery (RGS) using 99mTc-PSMA-I&S, with a high or unclear risk of bias.
- PSMA targeting was applied in salvage lymph node surgery (44.8%) and primary PCa surgery (41.4%), with specificity (median 98.9%) generally higher than sensitivity (median 84.8%).
- Oncological outcomes were reported in limited studies, primarily on salvage surgery, showing variable PSA decline and biochemical recurrence rates; clear oncological benefits remain unproven.
Conclusions:
- PSMA-targeted surgery, particularly salvage PSMA-RGS with 99mTc-PSMA-I&S, is under investigation for prostate cancer.
- While intraoperative PSMA targeting demonstrates high specificity, robust data on oncological benefits are still lacking.
- PSMA-targeted surgery is considered investigational due to the need for more solid outcome data.
