Deep learning can predict survival directly from histology in clear cell renal cell carcinoma

PLoS One. 2022 Aug 17;17(8):e0272656. doi: 10.1371/journal.pone.0272656. eCollection 2022.

Abstract

For clear cell renal cell carcinoma (ccRCC) risk-dependent diagnostic and therapeutic algorithms are routinely implemented in clinical practice. Artificial intelligence-based image analysis has the potential to improve outcome prediction and thereby risk stratification. Thus, we investigated whether a convolutional neural network (CNN) can extract relevant image features from a representative hematoxylin and eosin-stained slide to predict 5-year overall survival (5y-OS) in ccRCC. The CNN was trained to predict 5y-OS in a binary manner using slides from TCGA and validated using an independent in-house cohort. Multivariable logistic regression was used to combine of the CNNs prediction and clinicopathological parameters. A mean balanced accuracy of 72.0% (standard deviation [SD] = 7.9%), sensitivity of 72.4% (SD = 10.6%), specificity of 71.7% (SD = 11.9%) and area under receiver operating characteristics curve (AUROC) of 0.75 (SD = 0.07) was achieved on the TCGA training set (n = 254 patients / WSIs) using 10-fold cross-validation. On the external validation cohort (n = 99 patients / WSIs), mean accuracy, sensitivity, specificity and AUROC were 65.5% (95%-confidence interval [CI]: 62.9-68.1%), 86.2% (95%-CI: 81.8-90.5%), 44.9% (95%-CI: 40.2-49.6%), and 0.70 (95%-CI: 0.69-0.71). A multivariable model including age, tumor stage and metastasis yielded an AUROC of 0.75 on the TCGA cohort. The inclusion of the CNN-based classification (Odds ratio = 4.86, 95%-CI: 2.70-8.75, p < 0.01) raised the AUROC to 0.81. On the validation cohort, both models showed an AUROC of 0.88. In univariable Cox regression, the CNN showed a hazard ratio of 3.69 (95%-CI: 2.60-5.23, p < 0.01) on TCGA and 2.13 (95%-CI: 0.92-4.94, p = 0.08) on external validation. The results demonstrate that the CNN's image-based prediction of survival is promising and thus this widely applicable technique should be further investigated with the aim of improving existing risk stratification in ccRCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Artificial Intelligence
  • Carcinoma, Renal Cell* / diagnosis
  • Carcinoma, Renal Cell* / genetics
  • Deep Learning*
  • Humans
  • Kidney Neoplasms* / diagnosis
  • Kidney Neoplasms* / genetics
  • Neural Networks, Computer
  • Retrospective Studies

Grants and funding

This study was funded by the Federal Ministry of Health, Berlin, Germany (grant: Tumorverhalten-Praediktions-Initiative; grant holder: Titus J. Brinker, German Cancer Research Center; #2519DAT712). JNK is supported by the German Federal Ministry of Health (DEEP LIVER, #ZMVI1-2520DAT111) and the Max-Eder-Programme of the German Cancer Aid (#70113864). The sponsors had no role in the design and conduct of the study, collection, management, analysis and interpretation of the data, preparation, review or approval of the manuscript, and decision to submit the manuscript for publication.