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

• Published in: International journal of radiation oncology, biology, physics
• Main Authors: 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, Henkenberens, Christoph
• Format: Journal Article
• Language: English
• Published: United States 02.06.2022

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.