Introduction: PSMA-PET is considered the imaging of choice in patients with recurrent prostate cancer (PCa) after primary treatments. Recurrent PCa includes various clinical settings. Thus, we aimed to explore the oncologic benefit of second-line salvage PSMA-guided MDT (metastases directed treatment) in PCa patients with recurrence after previous salvage treatments and oligo-recurrent N1/M1a-b disease at PSMA-PET. Methods: We retrospectively analyzed patients underwent RP (radical prostatectomy) for PCa and PSMA-PET (from January 2016 to February 2021) performed for biochemical recurrence (BCR) after first-line salvage therapies for BCR after PR at 3 high volume European Centers. Oligo-recurrent (=3 lesions) patients with N1/M1a-b disease at PSMA-PET and eligible for MDT were identified. MDT consist of salvage lymph node dissection (sLND) and stereotactic body radiotherapy (SBRT) or combination of both. Conventional approach includes observation or androgen deprivation therapy. Men were stratified according to treatment after PSMA-PET (MDT vs. conventional approach). Kaplan Meier curves were used to assess progression free survival (PFS), metastases free survival (MFS) and CRPC free survival (CRPC-FS) at 3 years of follow up after stratifying according to treatment after PSMA-PET. Multivariable Cox regression was performed to identify independent predictors of progression and metastases. Results: Overall, 113 patients were enrolled: 91 patients were treated with MDT approach and 22 with conventional approach. The median (IQR) follow-up after PSMA-PET was 31 (19-42) months. Overall, no significant differences were found concerning 3-years PFS according to type of treatment (p=0.3). MFS and CRPC-FS estimates at 3 years were 73.5% and 94.7% in patients underwent MDT vs 30.5% and 79.5% in men treated with conventional approach, respectively (all p<0.001). At the multivariable Cox regression analysis, age (HR=0.96) and pT3b-pT4 (HR=2.02) were independent predictors of progression (all p=0.03), while MDT (HR 0.37) was the only independent predictor of metastases (p= 0.02). Conclusions: In a selected population of oligo-recurrent N1/M1a-b Pca patients with limited therapeutic chances due to previous salvage treatments, the MDT targeted to PSMA-PET may represent a promising second-line salvage approach to delay further progression to CRPC status. SOURCE OF Funding: None
