Toxicity and Patient Reported Quality of Life after PSMA-PET and mpMRT-Based Focal Dose Escalated Definitive Radiotherapy in Prostate Cancer Patients: 2-Year Follow-Up of the HypoFocal Phase II Trial

Abstract

The prospective, 2-armed non-randomized HypoFocal phase II trial investigates the safety and feasibility of focal dose escalated external beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) for prostate cancer (PCa) patients based on PSMA-PET and multiparametric MRI. This approach improves tumor coverage and thus putatively treatment effectiveness but leads to larger boost volumes. Here we present toxicity and patient reported quality of life (QoL) results after 2 years follow-up (FU) MATERIALS/METHODS: Patients with intermediate- or high-risk PCa and cN0/cM0 stage were included. Patients in arm A received 60 Gy in 20 fractions to the prostate with an integrated boost of up to 75 Gy. Patients in arm B received one session HDR-BT with 15 Gy to the prostate and a boost of up to 19 Gy, followed by EBRT of 44 Gy in 20 fractions. Boost volumes were defined by PSMA-PET and mpMRI based on validated approaches. Genitourinary (GU) and gastrointestinal (GI) toxicity (CTCAE v5.0) and QoL with IPSS and EORTC questionnaires (QLQ30 and PR25) were assessed. Fifty patients were treated in both arms in two centers (Freiburg and Berlin). Table 1 shows patients characteristics. In arm, A grade 2 GU and GI toxicity rates after 2 years were 8% and 4%. There were no grade 3 GU toxicities. Two patients experienced grade 3 GI toxicities due to multifactorial causes. In Arm B grade 2 GU and GI toxicity rates after 2 years were 17% and 0%. No grade 3 toxicities were observed in arm B. Toxicities were not statistically significantly different between baseline and 2y FU (p>0.055). QoL analysis was performed with patients with available questionnaires at baseline and 2y FU (12-15 in Arm A and 13-15 in Arm B). Only bowel function (p = 0.0005, median 4 vs 25 points) in Arm A and sexual- (p = 0.016, median 25 vs 50 points) and bowel function (p = 0.004, median 0 vs 8 points) and dyspnea (p = 0.031, median 0 vs 0 points) in Arm B decreased significantly after 2 year FU. Other QoL items were not significantly different. Bowel symptoms were significantly worse in Arm A compared to Arm B (p = 0.003). Median PSA values after 2 years were 0.23 ng/ml in Arm A and 0.33 ng/ml in Arm B. Despite large boost volumes, the 2 years FU of the HypoFocal-Phase II trials shows no significantly increased GU and GU toxicities compared to baseline symptoms. Patients reported about a good QoL but increased bowel symptoms after 2 years, particularly if treated with EBRT only. Implementation of PSMA-PET into focal dose escalated radiotherapy approaches appears safe and feasible. However, radioproctitis demands careful management. The current PSA values suggest a highly effective therapy, but longer FU is needed to evaluate oncological outcomes. The HypoFocal-SBRT phase III trial will evaluate the PSMA-PET and mpMRI-based focal dose escalated SBRT.