There are few markers to identify those likely to recur or progress after treatment with intravesical BCG. We developed and validated artificial intelligence-based histologic assays that extract interpretable features from transurethral resection of bladder tumor digitized pathology images to predict risk of recurrence, progression, development of BCG unresponsive disease, and cystectomy.
Pre-BCG resection-derived whole-slide images and clinical data were obtained for high-risk non-muscle invasive bladder cancer cases treated with BCG from 12 centers and were analyzed through a segmentation and feature extraction pipeline. Features associated with clinical outcomes were defined and tested on independent development and validation cohorts. Cases were classified into high or low risk for recurrence, progression, BCG unresponsive disease, and cystectomy.
944 cases (development:303, validation:641, median follow-up:36 months) representative of the intended use population were included (high-grade Ta:34.1%, high-grade T1:54.8%; carcinoma-in-situ only:11.1%, any carcinoma-in-situ:31.4%). In the validation cohort, "High recurrence risk" cases had inferior high-grade recurrence-free survival versus "Low recurrence risk" cases (HR 2.08, p<0.0001). "High progression risk" patients had poorer progression-free survival (HR 3.87, p<0.001) and higher risk of cystectomy (HR 3.35, p<0.001) than "Low progression risk". Cases harboring the BCG unresponsive disease signature had a shorter time to development of BCG unresponsive disease than cases without the signature (HR 2.31, p<0.0001). AI assays provided predictive information beyond clinicopathologic factors.
We developed and validated AI-based histologic assays that identify high-risk non-muscle invasive bladder cancer cases at higher risk of recurrence, progression, BCG unresponsive disease, and cystectomy, potentially aiding clinical decision-making.
The Journal of urology. 2024 Oct 09 [Epub ahead of print]
Yair Lotan, Viswesh Krishna, Waleed M Abuzeid, Bryn Launer, Sam S Chang, Vrishab Krishna, Siddhant Shingi, Jennifer B Gordetsky, Thomas Gerald, Solomon Woldu, Eugene Shkolyar, Dickon Hayne, Andrew Redfern, Lisa Spalding, Courtney Stewart, Eduardo Eyzaguirre, Shamsunnahar Imtiaz, Vikram M Narayan, Vignesh T Packiam, Michael A O'Donnell, Roger Li, Loic Baekelandt, Steven Joniau, Tahlita Zuiverloon, Mario I Fernandez, Marcela Schultz, Patrick J Hensley, Derek Allison, John A Taylor, Ameer Hamza, Ashish Kamat, Vivek Nimgaonkar, Snehal Sonawane, Daniel L Miller, Drew Watson, Damir Vrabac, Anirudh Joshi, Jay B Shah, Stephen B Williams
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Valar Labs, Palo Alto, CA, USA., Department of Urology, Vanderbilt University Medical Center, Nashville, TN, USA., Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Department of Urology, Stanford Medicine, Palo Alto, CA, USA., Department of Urology, University of Western Australia, Perth, Australia., Department of Medical Oncology, University of Western Australia, Perth, Australia., Department of Urology, University of Texas Medical Branch, Galveston, TX, USA., Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA., Department of Urology, Emory University School of Medicine, Atlanta, GA, USA., Department of Urology, University of Iowa, Iowa City, IA, USA., Department of Urology, Moffitt Cancer Center, Tampa, FL, USA., Department of Urology, UZ Leuven, Leuven, Belgium., Department of Urology, Erasmus University Medical Center, Rotterdam, Netherlands., Department of Urology, Clínica Alemana Universidad del Desarrollo, Santiago, Chile., Department of Pathology, Clínica Alemana Universidad del Desarrollo, Santiago, Chile., Department of Urology, University of Kentucky College of Medicine, Lexington, KY, USA., Department of Pathology, University of Kentucky College of Medicine, Lexington, KY, USA., Department of Urology, University of Kansas Medical Center, Kansas City, KS, USA., Department of Pathology, University of Kansas Medical Center, Kansas City, KS, USA., Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.