3362 - Androgen Deprivation Therapy (ADT) and Radiotherapy (RT) with Imaging Evaluation Longitudinally (ARIEL): Implications of Neoadjuvant ADT for Focal RT Boost In Prostate Cancer
Presenter(s)
Y. Song1,2, M. Rojo Domingo3, L. Nguyen1, C. C. Conlin4, N. Dhillon1, S. Do1, A. Dornisch1, J. Kim1, K. L. Lee5,6, J. Liu1, R. R. Mckay1, L. K. Mell1, A. J. Mundt Jr1, E. M. Qiao1, R. Rupareliya1, H. Schaub7, A. Schwartzman8, A. M. Dale4, and T. M. Seibert1,3; 1Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 2Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, CA, 3Department of Bioengineering, University of California San Diego, La Jolla, CA, 4Department of Radiology, University of California San Diego, La Jolla, CA, 5Department of Radiology, Cambridge University, Cambridge, United Kingdom, 6Department of Radiology, Taipei Veterans General Hospital, Taiwan, Taiwan, 7Moores Cancer Center, University of California San Diego, La Jolla, CA, 8Halicioglu Data Science Institute, University of California San Diego, La Jolla, CA
Purpose/Objective(s): Men with locally advanced prostate cancer (PC) are at risk of developing metastases and must be treated aggressively. Definitive radiotherapy (RT) with androgen deprivation therapy (ADT) is a standard of care. While prostate-specific antigen (PSA) levels are used to monitor response to treatment, they can lead to delays in identification of treatment failure. Better biomarkers to predict early recurrence and guide post-treatment care are warranted. Restriction Spectrum Imaging restriction score (RSIrs) is a quantitative biomarker that highlights restricted diffusion to distinguish cancerous tissue. The objective of the ARIEL trial (prospective, phase II, single arm) is to evaluate changes in RSIrs for identifying patients who experience early biochemical recurrence, or fail to reach a PSA nadir <0.5 ng/mL after RT.
Materials/Methods: Men receiving RT with ADT underwent MRI scans before any therapy (MRI #1), after ADT but before RT (MRI #2), and after RT (MRI #3). Prostate MRI segmentations underwent centralized review by a board-certified radiologist who drew PI-RADS v2.1 lesions. We measured volume changes before and after treatment, to determine whether tumor lesions shrank more or less than the prostate. We also computed quantitative changes in maximum RSIrs and mean apparent diffusion coefficient (ADC; the standard diffusion biomarker) for MRI #1 vs. MRI #2 and MRI #3.
Results: Of 123 patients, 26 patients were excluded (withdrew or declined ADT/RT). Prostate and lesion volume changed after ADT+RT: median decrease in prostate volume was 32% (IQR: 25-41%), and 73% (58-80%) for lesions. There were 96 visible lesions for MRI #1 and 78 for MRI #2. 60% of lesions visible prior to ADT remained clearly visible after ADT, and only 9% of lesions visible prior to ADT remained clearly visible after ADT and RT. Mean maximum RSIrs decreased after ADT (329 vs. 209; p<0.01), and even more after RT (329 vs.107; p<0.01). Mean ADC increased (p<0.01) from 914x10-6 mm2/s to 1064x10-6 mm2/s after ADT and RT (MRI #1 vs MRI #3), but was not significantly different for MRI #1 vs. MRI #2 (935x10-6 mm2/s; p=0.67).
Conclusion: ARIEL has completed accrual and preliminary results demonstrate significant changes to the prostate and lesions after ADT and RT, suggesting sensitivity of MRI to biological response to treatment. Observed decreases in RSIrs with treatment are generally concordant with expectations of high treatment efficacy. ADC changes were less harmonious. Follow-up is ongoing to assess whether observed variability in MRI response is related to future recurrence risk (primary endpoint). With neoadjuvant ADT, both pre-ADT and post-ADT MRI are necessary for accurate focal RT boost targeting. RT boost to the dominant lesion would be simpler with concurrent commencement of ADT and RT (only one MRI before RT).