PSMA MRI Guided prOstate SBRT (ARGOS)/Comprehensive, Longitudinal Evaluation of IMaging BiomarkErs Post Radiotherapy (CLIMBER) Phase I/II Trial.

Abstract

The ARGOS-CLIMBER trial is a multi-institutional phase 1/2 study utilizing a combined prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/magnetic resonance imaging (MRI) approach to treat dominant intraprostatic lesions and affected lymph nodes in unfavorable intermediate and high-risk prostate cancer using a 5 fraction SABR and simultaneous in-field boost (SIB) technique. Here we report on the primary endpoint of toxicity within 6 months of treatment. SIB volumes were defined utilizing a PET/MRI acquired using ¹⁸F-PSMA 1007. Five fraction SABR was planned to deliver doses (maximum SIB) to the prostate 35 Gy (50 Gy), seminal vesicles 25 Gy (50 Gy), and lymph nodes 25 Gy (35 Gy) while respecting organs at risk. Toxicity and quality of life (QOL) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 and Expanded Prostate Cancer Index Composite (EPIC-26) during radiation, at 6 weeks posttreatment, and at 6 months posttreatment. In total, 50 patients were treated, 23 patients had unfavorable intermediate-risk disease, 23 were high risk, and 4 were very high-risk prostate cancer. Median prostate SIB of 41.6 Gy (IQR, 39.3-44.8 Gy) was delivered to a median of 1 intraprostatic lesion. Eighteen patients received nodal treatment. There was a single acute grade 3 gastrointestinal (GI) toxicity of diarrhea and a single late grade 4 GI toxicity of bleeding. With a median follow-up of 12 months, the EPIC-26 scale showed an increase in urinary irritation (P < .001) and no differences for urinary incontinence (P = .12) and GI QOL (P = .65) and a decrease in hormonal/sexual QOL (P < .001 and P < .001). Mean ± SD prostate-specific antigen, maximum standardized uptake value on PET, and maximum MRI Prostate Imaging Reporting and Data System (PIRADS) scores at baseline to 6 months decreased from 15.4 (± 10.3) to 0.18 (± 0.40) ng/mL, 25.5 (± 19.5) to 4.5 (± 7.7), and 4.7 (± 0.6) to 2.9 (± 1.5), respectively. ARGOS-CLIMBER demonstrated acceptable 6-month toxicity using 5 fraction SABR with PET/MRI directed SIB to the prostate and lymph nodes.