The association of prostate-specific antigen (PSA) persistence after radical prostatectomy (RP) with inferior prognosis was demonstrated in a systematic review. However, all patients in the included studies lacked a prostate-specific membrane antigen Positron-Emissions-Tomography (PSMA-PET) before salvage radiotherapy (SRT). Since PSMA-PET has markedly improved sensitivity in detecting lymph node and distant metastases, it is unclear whether PSA persistence can be further considered a risk factor in patients or reflects an advanced tumor stage.
We used a retrospective database including 1222 PSMA-PET-staged prostate cancer patients treated with SRT for biochemical recurrence (BR) at 11 centers in five countries. After patients without information on PSA persistence were excluded, 1188 patients remained. The effects of PSA persistence and recurrence on overall survival (OS), metastasis-free survival (MFS), and biochemical progression-free survival (BPFS) were evaluated.
The median follow-up time was 31.0 months (IQR range: 20.04-43.6 months). PSMA-PET revealed a higher incidence of local recurrence (43.5% vs. 30.0%, p = 0.01), and lower incidence of nodal failure in patients with PSA recurrence (40.6% vs. 30.5%, p < 0.001). In univariate analysis, patients with PSA recurrence had significantly superior 3-year biochemical progression-free survival (BPFS) (71.5% vs. 63.0%, p = 0.033) and MFS (83.0% vs. 78.0%, p = 0.049) compared with patients with PSA persistence. In the multivariate analysis, no significant differences were observed concerning BPFS (p = 0.738), MFS, (p = 0.826), or OS (p = 0.730).
PSA persistence, traditionally considered a hallmark of a worse prognosis, may require reevaluation considering advances in imaging sensitivity. While our analysis does not definitively determine whether PSA persistence is no longer prognostic, it remains possible that its historically poorer prognosis and early focal detection via PSMA PET/CT have been therapeutically mitigated. As PSMA-PET becomes more widely available, its ability to detect hidden disease may help guide individualized treatment decisions.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2026 Jun 12 [Epub ahead of print]
Sophia Scharl, Reinhard Thamm, Constantinos Zamboglou, Iosif Strouthos, Andrea Farolfi, Francesca Serani, Stefan A Koerber, Jan C Peeken, Marco M E Vogel, Stephanie G C Kroeze, Matthias Guckenberger, Manuel Krafcsik, George Hruby, Louise Emmett, Nina-Sophie Schmidt-Hegemann, Christian Trapp, Simon K B Spohn, Christoph Henkenberens, Benjamin Mayer, Mohamed Shelan, Daniel M Aebersold, Nina Eberhardt, Jürgen Debus, Thomas Wiegel
Department of Radiation Oncology, University Hospital Ulm, Germany. Electronic address: ., Department of Radiation Oncology, University Hospital Ulm, Germany., Department of Radiation Oncology, Medical Center -Faculty of Medicine, University of Freiburg, Germany., Department of Radiation Oncology, German Oncology Center, University Hospital of the European University, Limassol, Cyprus., Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Unit of Nuclear Medicine, Department of Medicine -DIMED, University Hospital of Padua, Padova, Italy., Department of Radiation Oncology, Barmherzige Brüder Hospital Regensburg, Regensburg, Germany., Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich (TUM), Germany., Radiation Oncology Center KSA-KSB, Canton Hospital of Aarau, Aarau, Switzerland., Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Department of Radiation Oncology, Royal North Shore Hospital, University of Sydney, Sydney, Australia., St Vincent's Clinical School, University of New South Wales, Sydney, Australia., Department of Radiotherapy and Oncology, University Hospital, LMU Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich 81377 Munich, Germany; Bavarian Cancer Research Center (BZKF), Munich, Germany., Department of Radiotherapy and Oncology, University Hospital, LMU Munich, Germany., Department of Radiotherapy and Special Oncology, Medical School Hannover, Hannover, Germany., Institute for Epidemiology and Medical Biometry, University Ulm, Ulm, Germany., Department of Radiation Oncology, Inselspital Bern, University of Bern, Switzerland., Department of Nuclear Medicine, University Hospital Ulm, Germany., Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Clinical Cooperation Unit Radion Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.