Evaluation of imaging-based prognostication (IPRO) using artificial intelligence (AI) in stage IV colorectal cancer (CRC) patients treated with first-line (1L) systemic therapy

INTRODUCTION: Accurate prognostication in stage IV CRC informs treatment decisions and stratifies patients in clinical trials. Tumor, node, metastasis (TNM) staging derived from pre-treatment computed tomography (CT) imaging classifies extent of disease but may not fully characterize prognosis. IPRO-alpha is an AI-generated prognostic score derived from pre-treatment CT imaging, with higher scores representing improved survival. IPRO-alpha was trained and validated to predict survival in advanced non-small-cell lung cancer. This study evaluates generalizability and prognostic utility of IPRO-alpha in real-world stage IV CRC patients receiving 1L systemic therapy, compared to TNM substage. METHODS: We retrospectively evaluated IPRO-alpha and TNM substage in a real-world dataset of stage IV CRC patients treated with 1L systemic therapy between 2010-2018 at 17 cancer centers. We evaluated median overall survival (mOS) and hazard ratios (HR) using Cox proportional hazards models across stage IV substages (A, B, C) and matched relative distributions for IPRO-alpha. RESULTS: 372 patients had available pre-treatment CT and known TNM substage (IVA=141, IVB=162, IVC=69). The median age was 61 years (IQR 52-69), with 32.8% (n=122) females. TNM substage IVA mOS was significantly better than IVB, with no statistically significant difference between stage IVB and IVC (Table 1). Distribution-matched IPRO-alpha groups showed significant survival differences across high, intermediate and low scores. CONCLUSIONS: IPRO-alpha may stratify survival with greater prognostic discrimination than TNM substage in metastatic CRC patients. IPRO-alpha, trained on lung cancer data, learned shared prognostic features allowing generalizability of survival predictions to entirely different tumour sites. Future work will evaluate IPRO-alpha's ability to stratify survival in various CRC treatment subsets. Median OS for stage IV CRC patients stratified by TNM substage and IPRO-alpha survival scores. N mOS in months (95% CI) HR (95% CI) p-value IPRO-alpha High 141 24.0 (19.1-29.6) 0.74 (0.58-0.93) 0.010 IPRO-alpha Intermediate 162 17.9 (16.2-20.9) reference - IPRO-alpha Low 69 10.0 (7.4-13.0) 2.28 (1.70-3.06) < 0.001 Stage IVA 141 20.8 (17.9-27.5) 0.77 (0.61-0.98) 0.032 Stage IVB 162 17.2 (14.4-20.1) reference - Stage IVC 69 13.0 (10.9 - 16.0) 1.14 (0.85-1.53) 0.363