Abstract Introduction: Preoperative risk stratification of kidney cancer patients is critical for treatment selection and improving mortality rates. Current clinical approaches such as cancer grading are limited by inter-reviewer variability, require invasive biopsy procedures, and might not capture the full extent of patient risk. We sought to evaluate a deep learning (DL) model to quantify patient risk and prognosticate overall survival in kidney cancer patients via CT scans. Methods: This retrospective study used preoperative contrast CT scans from 4 public multi-institutional collections with date of death/censoring available. A deep learning (DL) network architecture was developed to analyze input CT scans via a convolutional feature extractor and a Cox proportional hazards-based cost function. The DL model assigned a risk score to each patient, with the median risk used as a cutoff for classifying patients as high-risk or low-risk. Model performance for prognosticating overall survival (OS) was evaluated separately in training, internal validation, and external validation cohorts via Kaplan-Meier analysis in terms of concordance index and hazard ratios, with risk groups compared via Wilcoxon log-rank tests (α = 0.05). Results: In the training/internal validation cohort (N=418, 8 institutions) and external validation cohort (N=102, 1 institution), the median age was 60 and 59 years, the male/female ratios were 62%/38% and 75%/25%, with a median follow up of 2.8 and 3.1 years, respectively. The DL model yielded a training c-index of 0.66 (95% CI: 0.63-0.68), internal validation c-index of 0.73 (95% CI: 0.70-0.76) and an external validation c-index of 0.67 (95% CI: 0.64-0.70). Kaplan-Meier analysis of associated survival curves based on DL-determined high- and low-risk patients demonstrated statistically significant separation in all cohorts: training (p = 0.003, HR = 8.63, 95% CI: 8.28-8.98), internal validation (p = 0.027, HR = 4.89, 95% CI: 4.52-5.26), and external validation (p = 0.01, HR = 6.54, 95% CI: 6.18-6.90). Baseline clinicopathological characteristics were not significantly different between DL high and low risk patients in external validation (chi-square testing; ISUP grade p=0.375, age p=0.824, race p=0.567, and sex p=0.440). ISUP grade was also not a significant predictor of OS in internal validation (HR=1.57, p=0.211, 95% CI: 1.28-1.85) or external validation (p = 0.465, HR=0.16, 95% CI: 0.33-0.74). Conclusion: A deep learning model based on pre-operative CT scans was found to accurately prognosticate overall survival in kidney cancers in a multi-institutional setting, independent of clinicopathological factors. This model is being validated on larger cohorts, and in the context of targeted therapies. Citation Format: Brennan Flannery, Mohsen Hariri, Thomas DeSilvio, Amir Sadri, Jane Nguyen, Erick M. Remer, Smitha Krishnamurthi, Satish E. Viswanath. Deep learning based risk stratification of pre-operative CT scans is prognostic of overall survival in kidney cancers [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 7379.
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