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<0.01), and to 107 (SD:61) post-RT (p<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.

Dr. Tyler Seibert reports honoraria or consulting fees from Varian Medical Systems, WebMD, MJH Life Sciences, MD Education USA, GE Healthcare, Blue Earth Diagnostics, Janssen, CorTechs Labs, and MyOme. He has stock options in CorTechs Labs, MyOme, and Open Medicine for serving on their scientific advisory boards. He receives research funding and/or in-kind research support from GE Healthcare, Blue Earth Diagnostics, Quibim, AIRA Matrix, Veracyte, and Lantheus, all through the University of California San Diego. These companies might potentially benefit from the research results. The terms of this arrangement have been reviewed and approved by the University of California San Diego in accordance with its conflict-of-interest policies. Dr. Anders Dale is a Founding Director and holds equity in CorTechs Labs, Inc. (DBA Cortechs.ai), Precision Pro, Inc., and Precision Health and Wellness, Inc. AMD is the President and a Board of Trustees member of the J. Craig Venter Institute (JCVI). He is a Professor II at Oslo University in Norway.

NCT04349501

This work was supported, in part, by the American Society for Radiation Oncology and the Prostate Cancer Foundation (ASTRO-PCF #PCF20YOUN01), as well as the National Institutes of Health (NIH/NIBIB K08EB026503; UL1TR000100).

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