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In Computer methods and programs in biomedicine

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 workload for the pathologist during the analysis of each sample, which is based on the pathologist's visual analysis of the morphology and organisation of the glands in the tissue, a time-consuming and subjective task. In recent years, with the development of digitisation devices, the use of computer vision techniques for the analysis of biopsies has increased. However, to the best of the authors' knowledge, the development of algorithms to automatically detect individual cribriform patterns belonging to Gleason grade 4 has not yet been studied in the literature. The objective of the work presented in this paper is to develop a deep-learning-based system able to support pathologists in the daily analysis of prostate biopsies. This analysis must include the Gleason grading of local structures, the detection of cribriform patterns, and the Gleason scoring of the whole biopsy.

METHODS : The methodological core of this work is a patch-wise predictive model based on convolutional neural networks able to determine the presence of cancerous patterns based on the Gleason grading system. In particular, we train from scratch a simple self-design architecture with three filters and a top model with global-max pooling. The cribriform pattern is detected by retraining the set of filters of the last convolutional layer in the network. Subsequently, a biopsy-level prediction map is reconstructed by bi-linear interpolation of the patch-level prediction of the Gleason grades. In addition, from the reconstructed prediction map, we compute the percentage of each Gleason grade in the tissue to feed a multi-layer perceptron which provides a biopsy-level score.

RESULTS : In our SICAPv2 database, composed of 182 annotated whole slide images, we obtained a Cohen's quadratic kappa of 0.77 in the test set for the patch-level Gleason grading with the proposed architecture trained from scratch. Our results outperform previous ones reported in the literature. Furthermore, this model reaches the level of fine-tuned state-of-the-art architectures in a patient-based four groups cross validation. In the cribriform pattern detection task, we obtained an area under ROC curve of 0.82. Regarding the biopsy Gleason scoring, we achieved a quadratic Cohen's Kappa of 0.81 in the test subset. Shallow CNN architectures trained from scratch outperform current state-of-the-art methods for Gleason grades classification. Our proposed model is capable of characterising the different Gleason grades in prostate tissue by extracting low-level features through three basic blocks (i.e. convolutional layer + max pooling). The use of global-max pooling to reduce each activation map has shown to be a key factor for reducing complexity in the model and avoiding overfitting. Regarding the Gleason scoring of biopsies, a multi-layer perceptron has shown to better model the decision-making of pathologists than previous simpler models used in the literature.

Silva-Rodríguez Julio, Colomer Adrián, Sales María A, Molina Rafael, Naranjo Valery


Convolutional neural networks, Cribriform, Deep learning, Gleason, Prostate cancer, Whole side images