334 - Validation of a Digital Pathology-Based Multimodal Artificial Intelligence Model in Oliogmetastatic Castration-Sensitive Prostate Cancer, including in Patients from the STOMP and ORIOLE Phase II Rando

P. Sutera¹, M. P. Deek², A. Mendes¹, Y. Song³, A. C. Shetty³, K. Van der Eecken⁴, E. Chen⁵, T. N. Showalter⁶, T. J. Royce⁷, T. Todorovic⁸, H. C. Huang⁹, S. Houck⁵, R. Yamashita⁵, A. P. Kiess¹⁰, D. Song¹, T. L. Lotan¹¹, A. Esteva⁹, F. Y. Feng¹², P. T. Tran¹³, and P. Ost¹⁴; ¹Johns Hopkins University School of Medicine, Baltimore, MD, ²Rutgers Cancer Institute of New Jersey, Department of Radiation Oncology, New Brunswick, NJ, ³University of Maryland, Baltimore, MD, ⁴Ghent University, Ghent, Belgium, ⁵Artera, Los Altos, CA, ⁶University of Virginia, Charlottesville, VA, ⁷The University of North Carolina at Chapel Hill, Chapel Hill, NC, ⁸Artera, Menlo Park, CA, United States, ⁹Artera, Mountain View, CA, ¹⁰Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, ¹¹Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, ¹²Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, ¹³Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, ¹⁴Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium

Purpose/Objective(s): Oligometastatic castration-sensitive prostate cancer (omCSPC) is a state of limited metastatic disease. Several randomized trials have demonstrated improvements in progression-free survival in patients with omCSPC treated with metastasis-directed therapy (MDT). However, clinical outcomes remain heterogenous and response to MDT is variable, raising the need for prognostic and predictive biomarkers. A multimodal artificial intelligence (MMAI) biomarker (ArteraAI Prostate Test) that leverages digital pathology and clinical variables was recently trained using data from patients with localized prostate cancer and found to be prognostic. Here, we evaluated this biomarker in omCSPC. Materials/

Methods: We performed an international multi-institution retrospective review of 221 men with omCSPC who were evaluated with MMAI scoring. The primary objective was to compare overall survival (OS) between patients with high- and low-MMAI score (stratified by median score). OS was defined as the time from diagnosis of omCSPC to death of any cause, calculated with the Kaplan-Meier method and compared using the log-rank test and Cox regression. The secondary objective was to evaluate MMAI score as predictive for MDT treatment effect in a subset of patients enrolled in the STOMP and ORIOLE randomized clinical trials. Given too few OS events for this subset, we evaluated MMAI for metastasis-free survival (MFS), defined as time of randomization to development of a new radiographically detected metastasis or death of any cause and analyzed using Cox regression. An interaction test was performed between treatment arm and MMAI score.
Results: Median follow-up of the surviving patients was 38.0 months. Patients with high MMAI (>0.527) were found to have higher PSA (5.8 vs 2.9, p=0.005), higher Gleason score (68.2% vs 38.8% Grade Group =4, p<0.001), more likely to have de novo metastatic disease (28.2% vs 8.1%, p<0.001), and more likely to have bone metastases (55.5% vs 39.6%, p=0.019). Patients with a high MMAI had a significantly worse OS (HR=4.38, 95% CI=1.24-15.56; p=0.022) with a median OS of 108.4 mo. vs “not reached” (p=0.012). In the STOMP and ORIOLE subset (N=51; median follow-up=61 months), MMAI was not prognostic for MFS (HR=1.24, 95% CI=0.64-2.43, p=0.52). MMAI however was predictive for MDT benefit as patients with high (HR=0.32, 95% CI=0.12-0.90; p=0.03), but not low (HR=1.59, 95% CI=0.63-4.04; p=0.33) MMAI demonstrated improvement in MFS when treated with MDT (p-interaction=0.02).
Conclusion: We have shown for the first time that the ArteraAI MMAI biomarker is prognostic for OS in patients with omCSPC. Further, MMAI appears to be predict benefit of MDT with high MMAI demonstrating a greater improvement in MFS following MDT over observation. Further work in validating these findings is warranted to allow for greater personalization in the management of patients with omCSPC.