Comprehensive Assessment of Tumor Stromal Heterogeneity in Bladder Cancer by Deep Learning and Habitat Radiomics.
Authors
Affiliations (5)
Affiliations (5)
- Department of Urology, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, China (Y.D., J.Y., B.W., Y.W.).
- Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou, China (Y.S.).
- Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou, China (Y.T., H.L.).
- Department of Pathology, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, China (J.C., X.J.).
- Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou, China (Y.T., H.L.). Electronic address: [email protected].
Abstract
Tumor stromal heterogeneity plays a pivotal role in bladder cancer progression. The tumor-stroma ratio (TSR) is a key pathological marker reflecting stromal heterogeneity. This study aimed to develop a preoperative, CT-based machine learning model for predicting TSR in bladder cancer, comparing various radiomic approaches, and evaluating their utility in prognostic assessment and immunotherapy response prediction. A total of 477 bladder urothelial carcinoma patients from two centers were retrospectively included. Tumors were segmented on preoperative contrast-enhanced CT, and radiomic features were extracted. K-means clustering was used to divide tumors into subregions. Radiomics models were constructed: a conventional model (Intra), a multi-subregion model (Habitat), and single-subregion models (HabitatH1/H2/H3). A deep transfer learning model (DeepL) based on the largest tumor cross-section was also developed. Model performance was evaluated in training, testing, and external validation cohorts, and associations with recurrence-free survival, CD8+ T cell infiltration, and immunotherapy response were analyzed. The HabitatH1 model demonstrated robust diagnostic performance with favorable calibration and clinical utility. The DeepL model surpassed all radiomics models in predictive accuracy. A nomogram combining DeepL and clinical variables effectively predicted recurrence-free survival, CD8+ T cell infiltration, and immunotherapy response. Imaging-predicted TSR showed significant associations with the tumor immune microenvironment and treatment outcomes. CT-based habitat radiomics and deep learning models enable non-invasive, quantitative assessment of TSR in bladder cancer. The DeepL model provides superior diagnostic and prognostic value, supporting personalized treatment decisions and prediction of immunotherapy response.