State of the Art in Prostate-specific Membrane Antigen-targeted Surgery-A Systematic Review

Abstract

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.

Keywords: Fluorescence-guided surgery; Image-guided surgery; Prostate cancer; Prostate-specific membrane antigen; Radioguided surgery.

Fig. 1

Schematic overview of clinical implementation of prostate-specific membrane antigen (PSMA)-guided surgery. Preoperative imaging can be either PSMA positron emission tomography (PET)/CT or single photon emission computed tomography (SPECT)/CT. CT = computed tomography; MRI = magnetic resonance imaging.

Fig. 2

PRISMA flowchart for literature search and selection. PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-analyses; PSMA = prostate-specific membrane antigen. ^aNonautomated. Records excluded by the author using Rayyan. ^bOnly abstract available.

Fig. 3

Bias table according to Risk Of Bias In Non-randomized Studies—of Interventions (ROBINS-I). (Case reports were excluded from this bias analysis.)

Fig. 4

An overview of all reviewed literature. (A) All tracers chronologically aligned with year(s) of publication. (B) An overview of prospective studies. The color matches the studied tracer in A. Position on the y axis indicates the year of publication. Position on the x axis indicates the type of prostate cancer studied. (C) Overview of studies that retrospectively analyzed the data. The color matches the studied tracer in A. Position on the y axis indicates the year of publication. Position on the x axis indicates the type of prostate cancer studied. (D) Sankey diagram entwined in Figure 4B and C showing the distribution between open and robot-assisted surgical procedures by the number of patients. The color matches the tracer that was studied. PSMA = prostate-specific membrane antigen, The double outline ‘=’ means only ex vivo measurements were performed; the solid outline ‘—’ means in and ex vivo measurements were performed.