Metastasis-free survival and patterns of distant metastatic disease after PSMA-PET-guided salvage radiotherapy in recurrent or persistent prostate cancer after prostatectomy.

Prostate specific membrane antigen positron-emission tomography (PSMA-PET) is increasingly used to guide salvage radiotherapy (sRT) in prostate cancer (PCa) patients with biochemical recurrence/persistence after prostatectomy. This work examines (i) metastasis-free survival (MFS) following PSMA-PET guided sRT and (ii) the metastatic patterns on PSMA-PET images after sRT.

This retrospective, multicenter (9 centers, 5 countries) study included patients referred for PSMA-PET due to recurrent/persistent disease after prostatectomy. Patients with distant metastases (DM) on PSMA-PET prior to sRT were excluded. Cox-regression was performed to assess the impact of clinical parameters on MFS. The distribution of PSMA-PET detected DM following sRT and their respective risk factors were analysed.

All (n=815) patients received intensity-modulated RT to the prostatic fossa. In case of PET-positive pelvic lymph nodes (PLN-PET, n=275, 34%), pelvic lymphatics had been irradiated. Androgen deprivation therapy had been given in 251 (31%) patients. The median follow-up after sRT was 36 months. The 2-/4-year MFS following sRT were 93%/81%. In multivariate analysis the presence of PLN-PET was a strong predictor for MFS (HR=2.39, p<0.001). Following sRT, DM were detected by PSMA-PET in 128/198 (65%) patients and two metastatic patterns were observed: 43% had DM in sub diaphragmatic paraaortic LNs (abdominal-lymphatic) whereas 45% in bones, 9% in supra diaphragmatic LNs and 6% in visceral organs (distant). Two distinct signatures with risk factors for each pattern were identified.

MFS in our study is lower compared to previous studies, obviously due to the higher detection rate of DM in PSMA-PET after sRT. Thus, it remains unclear whether MFS is a surrogate endpoint for overall survival in PSMA PET-staged patients in the post sRT setting. PLN-PET may be proposed as a new surrogate parameter predictive of MFS. Analysis of recurrence patterns in PET after sRT revealed risk factor signatures for two metastatic patterns (abdominal-lymphatic and distant), which may allow individualized sRT concepts in the future.

International journal of radiation oncology, biology, physics. 2022 Jun 02 [Epub ahead of print]

Constantinos Zamboglou, Iosif Strouthos, Joerg Sahlmann, Andrea Farolfi, Francesca Serani, Federica Medici, Letizia Cavallini, Alessio Guiseppe Morganti, Christian Trapp, Stefan A Koerber, Jan C Peeken, Marco M E Vogel, Kilian Schiller, Stephanie E Combs, Matthias Eiber, Alexis Vrachimis, Konstantinos Ferentinos, Simon K B Spohn, Simon Kirste, Christian Gratzke, Juri Ruf, Anca-Ligia Grosu, Francesco Ceci, Wolfgang P Fendler, Jonathan Miksch, Stephanie Kroeze, Matthias Guckenberger, Helena Lanzafame, Stefano Fanti, George Hruby, Thomas Wiegel, Louise Emmett, Nina Sophie Schmidt-Hegemann, Christoph Henkenberens

Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany; Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Germany; German Oncology Center, University Hospital of the European University, Limassol, Cyprus. Electronic address: ., Department of Radiation Oncology, German Oncology Center, University Hospital of the European University, Limassol, Cyprus., Institute of Medical Biometry and Statistics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany., Division of Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Division of Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Department of Radiation Oncology, University Hospital, LMU Munich., Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center, Heidelberg, Germany., Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich (TUM), Germany; Institute of Radiation Medicine (IRM), Department of Radiation Sciences (DRS), Helmholtz Zentrum, München, Germany; Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site Munich, Germany., Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich (TUM), Germany., Department of Nuclear Medicine, German Oncology Center, University Hospital of the European University, Limassol, Cyprus; C.A.R.I.C. Cancer Research & Innovation Center, Limassol, Cyprus., Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany; Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Germany., Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg, Germany., Department of Urology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany., Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany., Department of Nuclear Medicine, European Institute of Oncology, Milan, Italy., Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany., Department of Nuclear Medicine, University Hospital of Ulm, Ulm, Germany., Department of Radiation Oncology, University Hospital Zürich, University of Zürich, Switzerland., Division of Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Nuclear Medicine Unit, Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, Messina, Italy., Department of Radiation Oncology, Royal North Shore Hospital - University of Sydney, Australia., Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany., Department of Theranostics and Nuclear medicine, St Vincent's Hospital Sydney Australia; St Vincent's Clinical School, University of New South Wales, Sydney Australia., Department of Radiotherapy and Special Oncology, Medical School Hannover, Hannover, Germany.

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