Background and Objective:Prostate cancer is one of the most common diseases affecting men worldwide. The Gleason scoring system is the primary diagnostic and prognostic tool for prostate cancer. Furthermore, recent reports indicate that the presence of patterns of the Gleason scale such as the cribriform pattern may also correlate with a worse prognosis compared to other patterns belonging to the Gleason grade 4. Current clinical guidelines have indicated the convenience of highlight its presence during the analysis of biopsies. All these requirements suppose a great

Prostate cancer is one of the main diseases affecting men worldwide. The gold standard for diagnosis and prognosis is the Gleason grading system. In this process, pathologists manually analyze prostate histology slides under microscope, in a high time-consuming and subjective task. In the last years, computeraided-diagnosis (CAD) systems have emerged as a promising tool that could support pathologists in the daily clinical practice. Nevertheless, these systems are usually trained using tedious and prone-to-error pixel-level annotations of Gleason grades in the tissue. To alleviate the need of manual pixel-wise labeling, just a handful of works have been presented in the literature. Furthermore, despite the promising results achieved on global scoring the location of cancerous patterns in the tissue is only qualitatively addressed. These heatmaps of tumor regions, however, are crucial to the reliability of CAD systems as they provide explainability to the system's output and give confidence to pathologists that the model is focusing on medical relevant features. Motivated by this, we propose a novel weakly-supervised deep-learning model, based on self-learning CNNs, that leverages only the global Gleason score of gigapixel whole slide images during training to accurately perform both, grading of patch-level patterns and biopsy-level scoring. To evaluate the performance of the proposed method, we perform extensive experiments on three different external datasets for the patch-level Gleason grading, and on two different test sets for global Grade Group prediction. We empirically demonstrate that our approach outperforms its supervised counterpart on patchlevel Gleason grading by a large margin, as well as state-of-the-art methods on global biopsy-level scoring. Particularly, the proposed model brings an average improvement on the Cohen's quadratic kappa (κ) score of nearly 18% compared to full-supervision for the patch-level Gleason grading task. This suggests that the absence of the annotator's bias in our approach and the capability of using large weakly labeled datasets during training leads to higher performing and more robust models. Furthermore, raw features obtained from the patch-level classifier showed to generalize better than previous approaches in the literature to the subjective global biopsy-level scoring.

The annotation of large datasets is often the bottleneck in the successful application of artificial intelligence in computational pathology. Commonly, Whole Slide Images (WSIs) are sliced into patches and a machine learning model is trained in a supervised fashion to predict the label of each patch. Unfortunately it is time-consuming and expensive to obtain detailed patch-level annotations and for this reason recently Multiple Instance Learning (MIL) and Semi Supervised Learning (SSL) approaches are gaining popularity to train with fewer annotations. In this work we couple SSL and MIL to train a deep learning classifier which combines the advantages of both methods and overcomes their limitations. Our method is able to learn from the global WSI diagnosis and a combination of labeled and unlabeled patches. Furthermore, we propose and evaluate an efficient labeling paradigm that guarantees a strong classification performance when combined with our learning framework. We perform extensive experiments on three different public cancer datasets SICAPv2, PANDA and Camelyon16. The advantages of each model component as well as the efficient labeling technique are empirically proven and the performance gains in comparison to the SSL and MIL baselines are highlighted. We compare to the state-of-the-art and completely supervised training. With only a small percentage of patch labels our proposed model achieves a competitive performance on SICAPv2 (Cohen's kappa of 0.801 with 450 patch labels), PANDA (Cohen's kappa of 0.794 with 22,023 patch labels) and Camelyon16 (ROC AUC of 0.913 with 433 patch labels).

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Background and Objective:Prostate cancer is one of the main diseases affecting men worldwide. The Gleason scoring system is the primary diagnostic tool for prostate cancer. This is obtained via the visual analysis of cancerous patterns in prostate biopsies performed by expert pathologists, and the aggregation of the main Gleason grades in a combined score. Computer-aided diagnosis systems allow to reduce the workload of pathologists and increase the objectivity. Nevertheless, those require a large number of labeled samples, with pixel-level annotations performed by expert pathologists, to be developed. Recently, efforts have been made in the literature to develop algorithms aiming the direct estimation of the global Gleason score at biopsy/core level with global labels. However, these algorithms do not cover the accurate localization of the Gleason patterns into the tissue.These location maps are the basis to provide a reliable computer-aided diagnosis system to the experts to be used in clinical practice by pathologists.In this work, we propose a deep-learning-based system able to detect local cancerous patterns in the prostate tissue using only the global-level Gleason * This work was supported by the Spanish Ministry of Economy and Competitiveness through projects DPI2016-77869 and PID2019-105142RB-C21.