Automated deep-learning system for Gleason grading of prostate cancer using biopsies: a diagnostic study.

The Gleason score is the strongest correlating predictor of recurrence for prostate cancer, but has substantial inter-observer variability, limiting its usefulness for individual patients. Specialised urological pathologists have greater concordance; however, such expertise is not widely available. Prostate cancer diagnostics could thus benefit from robust, reproducible Gleason grading. We aimed to investigate the potential of deep learning to perform automated Gleason grading of prostate biopsies. In this retrospective study, we developed a deep-learning system to grade prostate biopsies following the Gleason grading standard. The system was developed using randomly selected biopsies, sampled by the biopsy Gleason score, from patients at the Radboud University Medical Center (pathology report dated between Jan 1, 2012, and Dec 31, 2017). A semi-automatic labelling technique was used to circumvent the need for manual annotations by pathologists, using pathologists' reports as the reference standard during training. The system was developed to delineate individual glands, assign Gleason growth patterns, and determine the biopsy-level grade. For validation of the method, a consensus reference standard was set by three expert urological pathologists on an independent test set of 550 biopsies. Of these 550, 100 were used in an observer experiment, in which the system, 13 pathologists, and two pathologists in training were compared with respect to the reference standard. The system was also compared to an external test dataset of 886 cores, which contained 245 cores from a different centre that were independently graded by two pathologists. We collected 5759 biopsies from 1243 patients. The developed system achieved a high agreement with the reference standard (quadratic Cohen's kappa 0·918, 95% CI 0·891-0·941) and scored highly at clinical decision thresholds: benign versus malignant (area under the curve 0·990, 95% CI 0·982-0·996), grade group of 2 or more (0·978, 0·966-0·988), and grade group of 3 or more (0·974, 0·962-0·984). In an observer experiment, the deep-learning system scored higher (kappa 0·854) than the panel (median kappa 0·819), outperforming 10 of 15 pathologist observers. On the external test dataset, the system obtained a high agreement with the reference standard set independently by two pathologists (quadratic Cohen's kappa 0·723 and 0·707) and within inter-observer variability (kappa 0·71). Our automated deep-learning system achieved a performance similar to pathologists for Gleason grading and could potentially contribute to prostate cancer diagnosis. The system could potentially assist pathologists by screening biopsies, providing second opinions on grade group, and presenting quantitative measurements of volume percentages. Dutch Cancer Society.

Bulten W ，Pinckaers H ，van Boven H ，Vink R ，de Bel T ，van Ginneken B ，van der Laak J ，Hulsbergen-van de Kaa C ，Litjens G ... -  《-》

Artificial intelligence for diagnosis and grading of prostate cancer in biopsies: a population-based, diagnostic study.

An increasing volume of prostate biopsies and a worldwide shortage of urological pathologists puts a strain on pathology departments. Additionally, the high intra-observer and inter-observer variability in grading can result in overtreatment and undertreatment of prostate cancer. To alleviate these problems, we aimed to develop an artificial intelligence (AI) system with clinically acceptable accuracy for prostate cancer detection, localisation, and Gleason grading. We digitised 6682 slides from needle core biopsies from 976 randomly selected participants aged 50-69 in the Swedish prospective and population-based STHLM3 diagnostic study done between May 28, 2012, and Dec 30, 2014 (ISRCTN84445406), and another 271 from 93 men from outside the study. The resulting images were used to train deep neural networks for assessment of prostate biopsies. The networks were evaluated by predicting the presence, extent, and Gleason grade of malignant tissue for an independent test dataset comprising 1631 biopsies from 246 men from STHLM3 and an external validation dataset of 330 biopsies from 73 men. We also evaluated grading performance on 87 biopsies individually graded by 23 experienced urological pathologists from the International Society of Urological Pathology. We assessed discriminatory performance by receiver operating characteristics and tumour extent predictions by correlating predicted cancer length against measurements by the reporting pathologist. We quantified the concordance between grades assigned by the AI system and the expert urological pathologists using Cohen's kappa. The AI achieved an area under the receiver operating characteristics curve of 0·997 (95% CI 0·994-0·999) for distinguishing between benign (n=910) and malignant (n=721) biopsy cores on the independent test dataset and 0·986 (0·972-0·996) on the external validation dataset (benign n=108, malignant n=222). The correlation between cancer length predicted by the AI and assigned by the reporting pathologist was 0·96 (95% CI 0·95-0·97) for the independent test dataset and 0·87 (0·84-0·90) for the external validation dataset. For assigning Gleason grades, the AI achieved a mean pairwise kappa of 0·62, which was within the range of the corresponding values for the expert pathologists (0·60-0·73). An AI system can be trained to detect and grade cancer in prostate needle biopsy samples at a ranking comparable to that of international experts in prostate pathology. Clinical application could reduce pathology workload by reducing the assessment of benign biopsies and by automating the task of measuring cancer length in positive biopsy cores. An AI system with expert-level grading performance might contribute a second opinion, aid in standardising grading, and provide pathology expertise in parts of the world where it does not exist. Swedish Research Council, Swedish Cancer Society, Swedish eScience Research Center, EIT Health.

Ström P ，Kartasalo K ，Olsson H ，Solorzano L ，Delahunt B ，Berney DM ，Bostwick DG ，Evans AJ ，Grignon DJ ，Humphrey PA ，Iczkowski KA ，Kench JG ，Kristiansen G ，van der Kwast TH ，Leite KRM ，McKenney JK ，Oxley J ，Pan CC ，Samaratunga H ，Srigley JR ，Takahashi H ，Tsuzuki T ，Varma M ，Zhou M ，Lindberg J ，Lindskog C ，Ruusuvuori P ，Wählby C ，Grönberg H ，Rantalainen M ，Egevad L ，Eklund M ... -  《-》

Artificial intelligence assistance significantly improves Gleason grading of prostate biopsies by pathologists.

Bulten W ，Balkenhol M ，Belinga JA ，Brilhante A ，Çakır A ，Egevad L ，Eklund M ，Farré X ，Geronatsiou K ，Molinié V ，Pereira G ，Roy P ，Saile G ，Salles P ，Schaafsma E ，Tschui J ，Vos AM ，ISUP Pathology Imagebase Expert Panel ，van Boven H ，Vink R ，van der Laak J ，Hulsbergen-van der Kaa C ，Litjens G ... -  《-》

Development and Validation of an Artificial Intelligence-Powered Platform for Prostate Cancer Grading and Quantification.

Huang W ，Randhawa R ，Jain P ，Iczkowski KA ，Hu R ，Hubbard S ，Eickhoff J ，Basu H ，Roy R ... -  《JAMA Network Open》

Development and Validation of a Deep Learning Algorithm for Gleason Grading of Prostate Cancer From Biopsy Specimens.

Nagpal K ，Foote D ，Tan F ，Liu Y ，Chen PC ，Steiner DF ，Manoj N ，Olson N ，Smith JL ，Mohtashamian A ，Peterson B ，Amin MB ，Evans AJ ，Sweet JW ，Cheung C ，van der Kwast T ，Sangoi AR ，Zhou M ，Allan R ，Humphrey PA ，Hipp JD ，Gadepalli K ，Corrado GS ，Peng LH ，Stumpe MC ，Mermel CH ... -  《-》