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Zamboglou, Constantinos; Strouthos, Iosif; Sahlmann, Joerg; Farolfi, Andrea; Serani, Francesca; Medici, Federica; Cavallini, Letizia; Morganti, Alessio Guiseppe; Trapp, Christian; Koerber, Stefan A.; Peeken, Jan C.; Vogel, Marco M. E.; Schiller, Kilian; Combs, Stephanie E.; Eiber, Matthias; Vrachimis, Alexis; Ferentinos, Konstantinos; Spohn, Simon K. B.; Kirste, Simon; Gratzke, Christian; Ruf, Juri; Grosu, Anca-Ligia; Ceci, Francesco; Fendler, Wolfgang P.; Miksch, Jonathan; Kroeze, Stephanie; Guckenberger, Matthias; Lanzafame, Helena; Fanti, Stefano; Hruby, George; Wiegel, Thomas; Emmett, Louise; Schmidt-Hegemann, Nina Sophie und Henkenberens, Christoph (2022): Metastasis-Free Survival and Patterns of Distant Metastatic Disease After Prostate-Specific Membrane Antigen Positron Emission Tomography (PSMA-PET)-Guided Salvage Radiation Therapy in Recurrent or Persistent Prostate Cancer After Prostatectomy. In: International Journal of Radiation Oncology Biology Physics, Bd. 113, Nr. 5: S. 1015-1024

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Abstract

Purpose: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) is increasingly used to guide salvage radiation therapy (sRT) in patients with prostate cancer and biochemical recurrence/persistence after prostatectomy. This work examined (1) metastasis-free survival (MFS) after PSMA-PET guided sRT and (2) the metastatic patterns on PSMA-PET images after sRT. Methods and Materials: 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 before sRT were excluded. Cox regression was performed to assess the effect of clinical parameters on MFS. The distribution of PSMA-PET detected DM after sRT and their respective risk factors were analyzed. Results: All (n = 815) patients received intensity modulated RT to the prostatic fossa. In the 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 after sRT were 93%/81%. In multivariate analysis, the presence of PLN-PET was a strong predictor for MFS (hazard ratio, 2.39;P < .001). After sRT, DM were detected by PSMA-PET in 128/198 (65%) patients, and 2 metastatic patterns were observed: 43% had DM in sub-diaphragmatic para-aortic LNs (abdominal-lymphatic), 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. Conclusions: MFS in our study is lower compared with 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 2 metastatic patterns (abdominal-lymphatic and distant), which may allow individualized sRT concepts in the future. (C) 2022 Elsevier Inc. All rights reserved.

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