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

ABSTRACT 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 97 patients met inclusion criteria and received ≥1 MRI. On central review, visible PI-RADS lesions were identified in 88 patients: 80 patients had one lesion, and 8 patients had two lesions. After neoadjuvant ADT, 40% of lesions were not clearly visible. Those still visible had shrank by median 55.8% (IQR: 42.8-69.0%), much more than the prostate volume decrease of 21.5% (11.9-31.6%). RSIrs maximum within visible lesions decreased from mean 329 (SD:185) pre-ADT to 209 (SD:125) pre-RT ( p