The devil is in the details: a small-lesion sensitive weakly supervised learning framework for prostate cancer detection and grading.

Prostate cancer (PCa) is a significant health concern in aging males, and the diagnosis depends primarily on histopathological assessments to determine tumor size and Gleason score. This process is highly time-consuming, subjective, and relies on the extensive experience of the pathologists. Deep learning based artificial intelligence shows an ability to match pathologists on many prostate cancer diagnostic scenarios. However, it is easy to make mistakes on some hard cases with small tumor areas considering the extensively high-resolution of whole slide images (WSIs). The absence of fine-grained and large-scale annotations of such small tumor lesions makes this problem more challenging. Existing methods usually perform uniform cropping of the foreground of WSI and then use convolutional neural networks as the backbone network to predict the classification results. However, cropping can damage the structure of tiny tumors, which affects classification accuracy. To solve this problem, we propose an Intensive-Sampling Multiple Instance Learning Framework (ISMIL), which focuses on tumor regions and improves the recognition of small tumor regions by intensively sampling the crucial regions. Experiments of prostate cancer detection show that our method achieves an area under the receiver operating characteristic curve (AUC) of 0.987 on the PANDA sets, which improves recall by at least 33% with higher specificity over the current primary methods for hard cases. The ISMIL also demonstrates comparable abilities to human experts on the prostate cancer grading task. Moreover, ISMIL has shown good robustness in independent cohorts, which makes it a potential tool to improve the diagnostic efficiency of pathologists.