Androgen Deprivation Therapy (ADT) and Radiotherapy (RT) with Imaging Evaluation Longitudinally (ARIEL) trial: protocol, early results, and implications of neoadjuvant ADT for focal RT boost in prostate cancer

Background: Men with aggressive, localized prostate cancer (PC) undergo definitive radiotherapy (RT) with androgen deprivation therapy (ADT). The prospective, phase II ARIEL trial evaluates a quantitative MRI biomarker, Restriction Spectrum Imaging restriction score (RSIrs), at three time points (before treatment, after ADT and after RT) for treatment response assessment. RSIrs highlights intracellular restricted diffusion and is correlated with high-grade PC. Design: Participants are men with unfavorable-intermediate-risk or high-risk localized PC undergoing definitive RT with neoadjuvant and concurrent ADT, and MRI-RSI acquisitions at three time points: before therapy, after neoadjuvant ADT but before RT, and after RT. The primary aim is to evaluate performance of RSIrs for identifying patients who will experience early biochemical recurrence. Change in RSIrs within visible tumors after ADT and RT is the primary independent variable. Results: <0.01). Conventional apparent diffusion coefficient (ADC) changes were less consistent. Follow-up is ongoing to assess whether imaging response is related to future recurrence risk. Conclusion: ARIEL has completed accrual and preliminary results demonstrate changes in RSIrs after treatment, which may indicate tumor response. Primary results will be presented when the primary endpoint is reached. With neoadjuvant ADT, both pre- and post-ADT MRI are likely necessary for accurate focal RT boost targeting. Concurrent commencement of ADT and RT simplifies workflows and facilitates accurate gross tumor volume delineation.