Safety and quality of life of PSMA-PET- and MRI-based focal dose escalated radiotherapy for intermediate- and high-risk prostate cancer: Primary endpoint analysis of the bi-centric phase II HypoFocal trial (ARO2020-01)

To present the primary endpoint results, toxicities and quality of life (QoL) after two-year follow-up (FU) of the HypoFocal Phase II trial. Intermediate- and high-risk prostate cancer (PCa) patients were treated with moderately hypofractionated radiotherapy (MHRT) of 60 Gy in 20 fractions and a focal-boost of up to 75 Gy in Arm A, or high-dose-rate-brachytherapy (HDR-BT) of 15 Gy to the whole-gland with a boost of up to 19 Gy, followed by external beam RT (EBRT) of 44 Gy in 20 fractions in Arm B. Boost was based on combined information by multiparametric-magentic-resonance-tomography (mpMRI) and positron-emission-tomography targeting prostate-specific-membrane-antigen (PSMA-PET). Genitourinary (GU) and gastrointestinal (GI) toxicities were assessed according to CTCAEv5.0. QoL was assessed with validated questionnaires (IPSS, QLQ-PR25 and QLQ-PR30). Twenty-five patients were treated with MHRT and 30 patients with HDR-BT + EBRT. At two-year-FU, the rate of grade 2 + GU and GI toxicity was 24 % and 8 % in Arm A and 10 % and 0 % in Arm B, respectively. Two grade 3 GI toxicities were reported in Arm A, which can be attributed to multifactorial genesis and interventions. QoL was good with significant and minimally-important-differences only in bowel symptoms in Arm A and sexual functioning in Arm B. One patient in each arm relapsed. Limitations are the relatively small sample size. This is the first trial do demonstrate safety and feasibility of focal dose-escalation based on mpMRI and PSMA-PET in MHRT and HDR-BT + EBRT in intermediate- and high-risk PCa. Particularly, HDR-BT offers good toxicity and QoL profiles. Radiation proctitis demands careful management.