We present a pioneering investigation into the application of deep learning techniques to analyze histopathological images for addressing the substantial challenge of automated prognostic prediction. Prognostic prediction poses a unique challenge as the ground truth labels are inherently weak, and the model must anticipate future events that are not directly observable in the image. To address this challenge, we propose a novel three-part framework comprising of a convolutional network based tissue segmentation algorithm for region of interest delineation, a contrastive learning module for feature extraction, and a nested multiple instance learning classification module. Our study explores the significance of various regions of interest within the histopathological slides and exploits diverse learning scenarios. The pipeline is initially validated on artificially generated data and a simpler diagnostic task. Transitioning to prognostic prediction, tasks become more challenging. Employing bladder cancer as use case, our best models yield an AUC of 0.721 and 0.678 for recurrence and treatment outcome prediction respectively.

Histopathology is a gold standard for cancer diagnosis under a microscopic examination. However, histological tissue processing procedures result in artifacts, which are ultimately transferred to the digitized version of glass slides, known as whole slide images (WSIs). Artifacts are diagnostically irrelevant areas and may result in wrong deep learning (DL) algorithms predictions. Therefore, detecting and excluding artifacts in the computational pathology (CPATH) system is essential for reliable automated diagnosis. In this paper, we propose a mixture of experts (MoE) scheme for detecting five notable artifacts, including damaged tissue, blur, folded tissue, air bubbles, and histologically irrelevant blood from WSIs. First, we train independent binary DL models as experts to capture particular artifact morphology. Then, we ensemble their predictions using a fusion mechanism. We apply probabilistic thresholding over the final probability distribution to improve the sensitivity of the MoE. We developed DL pipelines using two MoEs and two multiclass models of state-of-the-art deep convolutional neural networks (DCNNs) and vision transformers (ViTs). DCNNs-based MoE and ViTs-based MoE schemes outperformed simpler multiclass models and were tested on datasets from different hospitals and cancer types, where MoE using DCNNs yielded the best results. The proposed MoE yields 86.15% F1 and 97.93% sensitivity scores on unseen data, retaining less computational cost for inference than MoE using ViTs. This best performance of MoEs comes with relatively higher computational trade-offs than multiclass models. The proposed artifact detection pipeline will not only ensure reliable CPATH predictions but may also provide quality control.