Prognostic validation of a digital pathology-based multi-modal artificial intelligence (MMAI) biomarker in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the CHAARTED trial (ECOG-ACRIN EA3805).

5077 Background: The ArteraAI MMAI prognostic biomarker leverages histopathology images and clinical data to risk stratify patients (pts) with localized prostate cancer. This study aimed to validate the MMAI biomarker in mHSPC. Methods: The validation cohort included a subset of pts from the CHAARTED phase III randomized trial with known age at diagnosis, baseline PSA, T-stage, and available histopathology images. Baseline characteristics were compared to examine the balance between included and excluded patients. Using the existing MMAI model, scores were generated, and prognostic ability was evaluated for overall survival (OS) in Cox proportional hazard model. Four defined prognostic groups based on tumor volume (high (HV) vs. low (LV)) and metastatic stage at diagnosis (M1 vs. M0) were included: 1. M0LV, 2. M0HV, 3. M1LV, 4. M1HV. These clinical groups were evaluated using multivariable analysis (MVA) which included MMAI risk group and treatment. Results: A subset of the CHAARTED patient population had evaluable digital histopathological images, allowing inclusion in this study (N=456/790, 57.7%), of which 370 (81.1%) were classified as MMAI-high and 86 (18.9%) as MMAI-intermediate/low risk. Data were available from 394/456 pts for classification into M0LV (N=57), M0HV (N=29), M1LV (N=66), or M1HV (N=242). MMAI-high proportion among groups were 56.1%, 69.0%, 86.4% and 92.6%, respectively. Median follow-up of the censored patients was 4.1 (IQR: 3.3-5.0) yrs. The estimated 5-yr OS across MMAI high, intermediate, and low groups was 39%, 58%, 83%, respectively (log rank p=<0.001). On MVA, the MMAI-high risk group model associated with OS (HR: 1.77 (95% CI: 1.10-2.84) p=0.02) adjusting for treatment arm, volume status, and stage at diagnosis (Table 1). When compared to M0LV, HV subgroups were also associated with OS on MVA. Conclusions: The ArteraAI MMAI model was found to be prognostic for OS among men with mHSPC in CHAARTED. This effect persisted when controlling for treatment, metastatic burden, and metastatic status at diagnosis. On MVA, M0HV and M1HV also maintained prognostic value. This analysis is exploratory in nature, to be followed by development of a model optimized for advanced prostate cancer.Table: see text