Multimodal recurrence scoring system for prediction of clear cell renal cell carcinoma outcome: a discovery and validation study

Summary: Background: Improved markers for predicting recurrence are needed to stratify patients with localised (stage I–III) renal cell carcinoma after surgery for selection of adjuvant therapy. We developed a novel assay integrating three modalities—clinical, genomic, and histopathological—to improve the predictive accuracy for localised renal cell carcinoma recurrence. Methods: In this retrospective analysis and validation study, we developed a histopathological whole-slide image (WSI)-based score using deep learning allied to digital scanning of conventional haematoxylin and eosin-stained tumour tissue sections, to predict tumour recurrence in a development dataset of 651 patients with distinctly good or poor disease outcome. The six single nucleotide polymorphism-based score, which was detected in paraffin-embedded tumour tissue samples, and the Leibovich score, which was established using clinicopathological risk factors, were combined with the WSI-based score to construct a multimodal recurrence score in the training dataset of 1125 patients. The multimodal recurrence score was validated in 1625 patients from the independent validation dataset and 418 patients from The Cancer Genome Atlas set. The primary outcome measured was the recurrence-free interval (RFI). Findings: The multimodal recurrence score had significantly higher predictive accuracy than the three single-modal scores and clinicopathological risk factors, and it precisely predicted the RFI of patients in the training and two validation datasets (areas under the curve at 5 years: 0·825–0·876 vs 0·608–0·793; p