Metastasis-free survival and patterns of distant metastatic disease after PSMA-PET-guided salvage radiotherapy in recurrent or persistent prostate cancer after prostatectomy.
Int. J. Radiat. Oncol. Biol. Phys.113, 1015-1024 (2022)
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.