Deep learning-based pathology signature could reveal lymph node status and act as a novel prognostic marker across multiple cancer types.

Background: Identifying lymph node metastasis (LNM) relies mainly on indirect radiology. Current studies omitted the quantified associations with traits beyond cancer types, failing to provide generalisation performance across various tumour types.

Methods: 4400 whole slide images across 11 cancer types were collected for training, cross-verification, and external validation of the pan-cancer lymph node metastasis (PC-LNM) model. We proposed an attention-based weakly supervised neural network based on self-supervised cancer-invariant features for the prediction task.

Results: PC-LNM achieved a test area under the curve (AUC) of 0.732 (95% confidence interval: 0.717-0.746, P < 0.0001) in fivefold cross-validation of multiple cancer types, which also demonstrated good generalisation in the external validation cohort with AUC of 0.699 (95% confidence interval: 0.658-0.737, P < 0.0001). The interpretability results derived from PC-LNM revealed that the regions with the highest attention scores identified by the model generally correspond to tumours with poorly differentiated morphologies. PC-LNM achieved superior performance over previously reported methods and could also act as an independent prognostic factor for patients across multiple tumour types.

Discussion: We presented an automated pan-cancer model for predicting the LNM status from primary tumour histology, which could act as a novel prognostic marker across multiple cancer types.