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.
European urology oncology. 2026 May 18 [Epub ahead of print]
Donato Cannoletta, Elio Mazzone, Francesco Di Bello, Giovanna Pecoraro, Giuseppe Salfi, Riccardo Tellini, Francesco Barletta, Fabio Turco, Ursula Vogl, Paolo Dell'Oglio, Armando Stabile, Giorgio Gandaglia, Francesco Montorsi, Alberto Breda, Alberto Briganti, Arturo Chiti, Silke Gillessen, Gaetano Paone, Thomas Zilli, Andrea Gallina, Nicola Fossati
Urology Service, Department of Surgery, Ente Ospedaliero Cantonale, Lugano, Switzerland; Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy. Electronic address: ., Department of Urology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy., Department of Urology, Fundació Puigvert, Barcelona, Spain., Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland; Institute of Oncology Research (IOR), Bellinzona, Switzerland; Clinical and Translational Oncology, Scuola Superiore Meridionale, Naples, Italy., Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland; Institute of Oncology Research (IOR), Bellinzona, Switzerland., Urology Service, Department of Surgery, Ente Ospedaliero Cantonale, Lugano, Switzerland., Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland., Vita-Salute San Raffaele University, Department of Nuclear Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy., Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland., Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland; Division of Nuclear Medicine, Istituto di Diagnostica Integrata della Svizzera Italiana (IDISI), Ente Ospedaliero Cantonale, Bellinzona, Switzerland., Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland; Radiation Oncology, Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale, Bellinzona, Switzerland; Faculty of Medicine, University of Geneva, Geneva, Switzerland., Urology Service, Department of Surgery, Ente Ospedaliero Cantonale, Lugano, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.