Utility of PSMA PET Guided Metastasis-Directed Radiotherapy

Abstract

Metastasis-directed radiotherapy (MDT) is becoming a mainstay in the management of oligometastatic prostate cancer (PCa), and PSMA-PET is currently the most sensitive imaging modality for PCa metastasis screening. The efficacy of MDT guided by PSMA-PET imaging has not yet been well characterized. Moreover, the optimal role of androgen deprivation therapy (ADT) in the context of MDT is not known. We sought to assess the efficacy of PSMA PET-guided MDT in patients with metastatic PCa treated with and without ADT. This is a single institutional retrospective study of patients diagnosed with metastatic prostate cancer by PSMA-PET imaging who were treated with MDT. Biochemical progression was defined as a PSA increase of ≥ 25% and ≥ 2 ng/mL if PSA was ≥ 2 ng/mL at time of initiating salvage treatment, or a PSA increase of ≥ 25% if PSA was < 2 ng/mL at time of salvage treatment. Survival analyses were performed using the Kaplan-Meier method with log-rank testing for significance. Cumulative incidence analyses were performed with Gray's testing for significance. Adverse event data were assessed per CTCAE v5 guidelines. A total of 196 PSMA PET-avid lesions from 101 patients were irradiated with stereotactic body radiotherapy (SBRT). Median time from prior definitive locoregional therapy to MDT was 6.2 years. 79 patients had hormone-sensitive PCa (HSPC) and 22 patients had castration-resistant PCa (CRPC) at time of MDT. 47 of 79 (59%) patients with HSPC received ADT along with MDT, and 20 of the 47 patients received augmented ADT. 25 of the 32 (78%) HSPC patients receiving MDT without ADT had undergone at least one prior course of ADT, and none had castrate levels of testosterone at time of MDT with a median testosterone level of 341 ng/dl. With a median follow-up of 22.4 months, 5 of 196 lesions (2.6%) demonstrated radiographic progression. 2-year cumulative incidence of progression from HSPC to CRPC was 11% in patients who received ADT at time of MDT and 35% in those who did not (P = 0.027). Median biochemical progression free survival of patients with CRPC, HSPC treated without ADT, and HSPC treated with ADT following MDT was 5.4, 7.6, and 43.9 months respectively (P<0.0001). 2-year overall survival of the abovementioned groups was 72.2%, 100%, and 97.5% respectively (P<0.001). No Grade 3-5 adverse effects were observed. MDT guided by PSMA-PET imaging is well-tolerated and delays biochemical progression in patients with CRPC and HSPC, with a greater effect observed in patients also receiving ADT.