Abstract 6223: Personalized MRI-informed forecasting of prostate cancer progression during active surveillance
Authors: Gomez Guillermo Lorenzo , Wu Chengyue , Yung Joshua P. , Ward John F. , Gomez Hector , Reali Alessandro , Yankeelov Thomas E. , Venkatesan Aradhana M. , Hughes Thomas J. 
Published: March 2024

Abstract
Low and intermediate-risk prostate cancer (PCa) patients are eligible for active surveillance (AS), whereby treatment is delayed until progression to higher-risk disease is detected via longitudinal multiparametric magnetic resonance imaging (mpMRI) scans, biopsies, and prostate specific antigen (PSA) tests. However, AS relies on a population-based observational paradigm in which standard testing frequencies may not match the patient’s tumor dynamics, resulting in a delayed diagnosis of progressive disease. To address these issues, we propose to advance AS towards a patient-specific predictive paradigm by leveraging computational tumor forecasts obtained with a biomechanistic model informed by mpMRI and clinical data collected during standard AS.
Here, we present a retrospective study with n = 16 PCa cases. All patients had three mpMRI scans obtained over 2.6 to 5.6 years during AS. Our biomechanistic model describes PCa growth in terms of the dynamics of tumor cell density as a combination of tumor cell mobility and net proliferation. The model is defined on the patient’s prostate geometry, which is segmented on T2-weighted MRI data. Tumor cell density estimates are derived from apparent diffusion coefficient (ADC) maps obtained from diffusion-weighted MRI data. To facilitate modeling, the longitudinal imaging datasets are non-rigidly co-registered for each patient. We initialize the model with the tumor cell density map obtained from the ADC map of the first scan. The model is parameterized by minimizing the model-data mismatch in tumor cell density at the second scan date, and then we perform a tumor forecast up to the third scan date. Finally, we build a logistic classifier from a panel of model-based biomarkers calculated from the personalized model forecasts (e.g., tumor volume, total proliferation activity) at the times of histopathological assessment (i.e., biopsy, surgery) to classify tumors as low risk (Gleason score 3+3, n = 16) or intermediate-high risk (Gleason score ≥ 3+4, n = 15).
We obtained a concordance correlation coefficient (CCC) for tumor volume of 0.89 at both model calibration and forecasting horizon. The spatial fit of tumor cell density yielded a median Dice score and CCC of 0.80 and 0.59 at the second mpMRI date, and of 0.76 and 0.60 at the third mpMRI date, respectively. The logistic classifier of PCa risk yielded an area under the ROC curve of 0.90 and operates at optimal sensitivity, specificity, and accuracy of 86.7%, 93.8%, and 90.3%, respectively. The time trajectories of PCa risk obtained from the temporal predictions of the model-based biomarkers enabled identification of PCa progression by more than 1 year. Thus, while further development and validation over larger cohorts are required, these results suggest that our forecasting technology is a promising tool to predict PCa progression in AS and, hence, optimally guide monitoring and treatment decisions during AS.
Citation Format: Guillermo Lorenzo Gomez, Chengyue Wu, Joshua P. Yung, John F. Ward, Hector Gomez, Alessandro Reali, Thomas E. Yankeelov, Aradhana M. Venkatesan, Thomas J. Hughes. Personalized MRI-informed forecasting of prostate cancer progression during active surveillance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6223.