Randomized trial of five or two MRI-guided adaptive radiotherapy treatments for prostate cancer (FORT).
Authors: Marciscano Ariel E. E. , Zhou Xi K. , Wolfe Sydney , Kishan Amar Upadhyaya , Steinberg Michael L. , Camilleri Philip , Nauseef Jones T. , Molina Ana M. , Sternberg Cora N. , Nanus David M. , Tagawa Scott T. , Margolis Daniel , Osborne Joseph , McClure Timothy D , Hu Jim C. , Scherr Douglas , Barbieri Christopher , Nagar Himanshu 
Published: March 2023

TPS399 Background: The objective of this randomized clinical trial is to demonstrate that 2 treatments of real-time MRI-guided radiotherapy (RT) does not significantly increase patient-reported GI and GU symptoms compared to 5 treatments of RT 2 years after treatment completion (24 months). Methods: Key Eligibility Criteria: Inclusion Criteria 1. Men aged > 18 with histologically confirmed low or intermediate risk prostate cancer per NCCN guidelines. 2. ECOG 0 – 1 3. IPSS < 18 4. Ability to receive MRI-guided radiotherapy. 5. Ability to complete the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Exclusion Criteria 1. Prior history of receiving pelvic RT. 2. Patient with history of IBD. 3. Hip replacements. 4. History of bladder neck or urethral stricture. 5. TURP < 8 weeks prior to RT 6. Metastatic (pelvic nodal or distant) disease on CT, Bone, and/or PSMA PET scan. Study Design/Endpoints: This is a randomized phase II non-inferiority trial comparing 2 fractions of ultrahypofractionated RT (25 Gy total with optional PSMA/MRI boost to 28 Gy) versus 5 fractions of ultra-hypofractionated RT (37.5 Gy total with optional PSMA/MRI boost to 45 Gy) in the definitive setting for prostate cancer. Subjects will be stratified based on pre-specified stratification factors and randomized 1:1 to receive 2 or 5 fractions using permuted block randomization. The primary endpoint is the change in patient-reported GI and GU symptoms as measured by EPIC at 2 years from end of treatment. Secondary endpoints will include both the safety endpoints including change in GI and GU symptoms at 3, 6, 12 and 60 months from end of treatment, and multiple efficacy endpoints including time to progression, prostate cancer specific survival and overall survival. Sample Size: The sample size is calculated based on a non-inferiority design. The non-inferiority margins are set to be a change score of 6 points for the GI symptoms and 5 points for the GU symptoms. The standard deviations of the change scores are assumed to be 13.2 for the GI symptoms and 10.5 for the GU symptoms based on estimates generated in RTOG 0415 trial. This level of change in scores are deemed as clinically meaningful. For example, 6 points of change score for GI symptoms corresponds to two symptoms worsening by 1 level (i.e., loose stools and frequency of bowel movements change from “no problem” to “very small problem”) or one of the symptoms worsening by 2 levels (i.e., loose stool change from “no problem” to “small problem”). A sample size of 122 with 61 in each arm will ensure 80% power for GI endpoint and 83% power for GU endpoint to detect non-inferiority using a one-sided two-sample t-test at the significance level of 0.05. Adjusting for a projected 10% EPIC/non-compliance rate, 136 patients (68 per arm) will be randomized. Stratification Factors: Patients will be stratified according to baseline EPIC bowel and urinary domain scores and country of treatment. Enrollment: Eleven patients. Clinical trial information: NCT04984343 .