The impact of PSMA-PET on Oncologic Control in Prostate Cancer Patients Who Experienced PSA Persistence or Recurrence

Abstract Background: Prostate Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) is currently recommended to restage prostate cancer (PCa) and to guide the delivery of salvage treatments. We aim to evaluate the oncologic outcomes of patients with recurrent PCa who received PSMA-PET. Methods: 324 hormone-sensitive PCa with PSA relapse after radical prostatectomy who underwent PSMA-PET in 3 high-volume European Centres. Patients have been stratified as pre-salvage setting who never received salvage treatments (n=134) and post-salvage setting, including patients who received previous salvage therapies (n=190). Patients with oligorecurrent (≤ 3 lesions) PSMA-positive disease underwent PSMA-directed treatments: salvage radiotherapy (sRT) or Metastases-directed therapy (MDT). Patients with polirecurrent (>3 lesions) PSMA-positive disease were treated with systemic therapy. Patients with negative PSMA-PET were treated with sRT or systemic therapies or observation according to the treating physician preferences. The primary outcome of the study was Progression-free survival (PFS). Secondary outcomes were: Metastases-free survival (MFS) and Castration Resistant Pca free survival (CRPC-FS). Kaplan-Meier analyses assessed PFS, MFS and CRPC-FS in the pre-salvage and post-salvage setting. Multivariable Cox regression models identified predictors of progression and metastatic disease. Results: Median follow up was 23 months (IQR: 10-34 months). In pre-salvage setting, the PFS, MFS and CRPC-FS estimates at 3 years were 66.2% vs. 38.9%, 95.2% vs 73.7% and 94.9% vs 93.1% in patients with negative vs. positive PSMA-PET, respectively (all p≥0.2). In post-salvage setting, the PFS, MFS and CRPC-FS estimates at 3 years were 59.5% vs. 29.1%, 92.7% vs. 65.1% and 98.8% vs 88.8% in patients with negative vs. positive PSMA-PET, respectively (all p≤0.01). At multivariable analyses, a positive PSMA-PET was an independent predictor of progression (HR=2.15) and metastatic disease (HR 2.37; all p≤0.03). Conclusion: PSMA-PET in recurrent PCa detects the site of recurrence guiding salvage treatments and has a prognostic role in patients who received previous salvage treatments.