Implementation of PSMA-PET in focal dose-escalated radiotherapy of primary prostate cancer patients: Results of a planned safety analysis of a phase II trial.

260 Background: Positron emission tomography targeting prostate specific membrane antigen (PSMA-PET) changes treatment management of primary prostate cancer (PCa) patients and might improve focal dose escalation in radiotherapy (RT) due to superior coverage of intraprostatic tumour burden. The 2-armed, non-randomized HypoFocal phase II trial investigates the safety of implementation of PSMA-PET-based focal therapy planning in external beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT). Here we present results from the planned safety analysis after 6 months of follow-up (FU). Methods: Intermediate- and high risk PCa Patients with cN0 and cM0 staged by mpMRI and PSMA PET were included. EBRT was delivered in 20 fractions with 60 Gy to the prostate and up to 75 Gy to mpMRI- and PSMA-PET defined boost volumes (arm A). HDR-BT was delivered with 15 Gy to the prostate and a boost of up to 19 Gy, followed by EBRT with 44Gy in 20 fractions (arm B). 36% of patients received androgen deprivation therapy. Volumes, treatment plans, gastrointestinal (GI) and genitourinary (GU) toxicities according to CTCAE v5.0 and Quality of Life (QoL) was assessed. Results: 25 patients were enrolled in each study arm in two centers (Freiburg and Berlin). Clinical T stage was significantly different between mpMRI and PSMA-PET (p=0.007) with upstaging towards ≥ cT2c stages in PET. GTV-PET and GTV-Union were significantly larger than GTV-MRI, resulting in large boost volumes (see table). Boost volumes received a median mean dose of 70 Gy in EBRT and a median D90 of 19 Gy in HDR-BT At 6 months FU, prevalence of ≥ grade 2 GU and GI toxicity was 4% and 0% for arm A and 12 and 4% for arm B. Two patients experienced grade 3 GI toxicitiy 9 and 12 months after RT, related to biopsy. No signification change of QoL was observed after 6 months of FU. cT stages and target volumes. Conclusions: Implementation of PSMA-PET in primary PCa patients relevantly alters cT-stage and RT treatment management with significantly larger GTVs and subsequent boost volumes. Still, boost delivery was feasible with acceptable acute toxicities and good QoL. Putative oncological benefits should be evaluated in larger cohorts. Clinical trial information: DRKS00017570. [Table: see text]