Between 30%-40% of patients with prostate cancer experience disease recurrence following radical prostatectomy. Existing clinical models for recurrence risk prediction do not account for population-based variation in the tumor phenotype, despite recent evidence suggesting the presence of a unique, more aggressive prostate cancer phenotype in African American (AA) patients. We investigated the capacity of digitally measured, population-specific phenotypes of the intratumoral stroma to create improved models for prediction of recurrence following radical prostatectomy.
This study included 334 radical prostatectomy patients subdivided into training (VT, n = 127), validation 1 (V1, n = 62), and validation 2 (V2, n = 145). Hematoxylin and eosin-stained slides from resected prostates were digitized, and 242 quantitative descriptors of the intratumoral stroma were calculated using a computational algorithm. Machine learning and elastic net Cox regression models were constructed using VT to predict biochemical recurrence-free survival based on these features. Performance of these models was assessed using V1 and V2, both overall and in population-specific cohorts.
An AA-specific, automated stromal signature, AAstro, was prognostic of recurrence risk in both independent validation datasets [V1,AA: AUC = 0.87, HR = 4.71 (95% confidence interval (CI), 1.65-13.4), P = 0.003; V2,AA: AUC = 0.77, HR = 5.7 (95% CI, 1.48-21.90), P = 0.01]. AAstro outperformed clinical standard Kattan and CAPRA-S nomograms, and the underlying stromal descriptors were strongly associated with IHC measurements of specific tumor biomarker expression levels.
Our results suggest that considering population-specific information and stromal morphology has the potential to substantially improve accuracy of prognosis and risk stratification in AA patients with prostate cancer.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2020 Mar 05 [Epub ahead of print]
Hersh K Bhargava, Patrick Leo, Robin Elliott, Andrew Janowczyk, Jon Whitney, Sanjay Gupta, Pingfu Fu, Kosj Yamoah, Francesca Khani, Brian D Robinson, Timothy R Rebbeck, Michael Feldman, Priti Lal, Anant Madabhushi
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California., Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio., Department of Pathology, Case Western Reserve University, Cleveland, Ohio., Department of Urology, Case Western Reserve University, Cleveland, Ohio., Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio., Moffitt Cancer Center & Research Institute and Department of Radiation Oncology, University of South Florida, Tampa, Florida., Departments of Pathology and Laboratory Medicine and Urology, Weill Cornell Medicine, New York, New York., T.H. Chan School of Public Health and Dana Farber Cancer Institute, Harvard University, Boston, Massachusetts., Department of Pathology, University of Pennsylvania, Philadelphia, Pennsylvania., Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio. .