In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 26, No. 8 ( 2020-04-15), p. 1915-1923
Abstract:
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. Experimental Design: 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. Results: 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. Conclusions: 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.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.CCR-19-2659
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2020
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
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