Randomized trial of MRI-guided salvage radiotherapy for prostate cancer in 4 weeks vs. 2 weeks (SHORTER).
Authors: Marciscano Ariel E. E. , Zhou Xi K. , Barbieri Christopher , Hu Jim C. , Scherr Douglas , Wolfe Sydney , Formenti Silvia , Nauseef Jones T. , Sternberg Cora N. , Molina Ana M. , Nanus David M. , Tagawa Scott T. , Nagar Himanshu 
Published: March 2023

TPS400

Background: The objective of this randomized clinical trial is to demonstrate that 2 weeks (5 fractions) of real-time MRI-guided radiotherapy (RT) with an MR Linac does not significantly increase patient-reported GI and GU symptoms compared to 4 weeks (20 fractions) of RT 2 years after treatment completion. Methods: Key Eligibility Criteria: Inclusion Criteria 1. Men aged > 18 with histologically confirmed prostate cancer after prostatectomy with detectable PSA. 2. KPS > 70. 3. Patients with no evidence of distant metastatic disease on PET/CT/MRI/bone scan< 180 days prior to enrollment. 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. History of bladder neck or urethral stricture. Study Design/Endpoints: This is a randomized phase II non-inferiority trial comparing 5 fractions of ultrahypofractionated RT (32.5 Gy total with optional PSMA/MRI boost to 40 Gy) versus 20 fractions of hypofractionated RT (55 Gy total with optional PSMA/MRI boost to 60 Gy) in the post-operative setting for prostate cancer. Subjects will be stratified based on pre-specified stratification factors and randomized 1:1 to receive 5 or 20 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 use of nodal treatment and ADT. Enrollment: 91 patients. Clinical trial information: NCT04422132 .