The Diagnostic Role of Prostate-specific Membrane Antigen Positron Emission Tomography for Patients with Rising PSA...

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is increasingly used for prostate cancer staging. However, the diagnostic role of molecular imaging for patients with rising prostate-specific antigen (PSA) levels following radical prostatectomy and postoperative radiation therapy remains unknown. We performed a systematic review and meta-analysis to assess the diagnostic performance and recurrence patterns detected by PSMA PET in this specific setting.

PubMed/MEDLINE, Cochrane library's Central, EMBASE, and Scopus were searched from database inception to September 1, 2025. Studies reporting PSMA PET findings in men with rising PSA levels after radical prostatectomy and postoperative radiotherapy were included. Pooled detection rates were calculated using random-effects meta-analysis. Site-specific recurrence patterns and PSA-dependent positivity were analyzed. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2, and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation.

A total of eight studies including 940 patients were analyzed. The pooled PSMA PET positivity rate was 83% (95% confidence interval [CI]: 0.75-0.89), with significant heterogeneity. When stratified by site, positivity rates were 7% for local recurrence, 42% for nodal disease, and 31% for distant metastases. PSMA PET positivity increased with PSA level, from approximately 72% at a PSA level of 0.2 ng/ml to >90% at a PSA level of ≥2.0 ng/ml. Interpretation is limited due to heterogeneity, observational designs, and incomplete reporting of key clinical variables.

The use of PSMA PET demonstrates high detection rates in men with rising PSA following radical prostatectomy and postoperative radiation therapy, even at low PSA levels. Recurrence is rarely located in the prostatic bed and more commonly involves nodal or distant sites. Despite limitations in evidence certainty, these findings support PSMA PET as a valuable restaging tool in this setting and underscore the need for further studies to optimize its timing and integration into salvage treatment strategies.

In this study we explored how well the PSMA PET works as a diagnostic tool in the setting of a PSA increase after radical prostatectomy plus radiotherapy. We found that PSMA PET was informative about the location of recurrence at an early stage, even at low PSA levels. These results may help clinicians in the early diagnosis of recurrent prostate cancer and in potential salvage treatments.