Sol Erika Boman

Xiaoyi Ji, Renata Zelic, Oskar Aspegren et al.

Artificial intelligence (AI) is becoming a clinical tool for prostate pathology, but generalization across variations in sample preparation and preservation over prolonged time periods remains poorly understood. We evaluated GleasonAI, an end-to-end attention-based multiple instance learning model, on an independent validation cohort comprising 10,366 biopsy cores from 1,028 patients across 14 Swedish regions, using archival diagnostic specimens from the ProMort cohorts collected between 1998-2015. The model achieved an overall quadratic-weighted kappa of 0.86 for core-level ISUP grading, comparable to several experienced pathologists and consistent across geographic regions. Notably, performance remained stable across the 17-year collection period, demonstrating robustness to time-related variation in archival material, a property not consistently observed with foundation model-based approaches, with exploratory analysis demonstrating a significant prognostic gradient across AI-assigned grade groups for prostate cancer-specific mortality. These findings support the generalizability of the AI grading model and demonstrate the potential of pathology archives as a large-scale resource for AI development, validation, and retrospective prognostic research.

Sol Erika Boman

Conformal prediction is a useful and versatile alternative to model calibration in machine learning classification. It replaces single-class prediction with prediction sets, guaranteeing that the \textit{a priori} probability of the prediction sets containing the true class is larger than or equal to a pre-specified rate. The size and usefulness of the prediction sets relies heavily on the choice of the non-conformity score function. The scientific literature contains many examples of non-conformity score functions but there is an absence of studies examining their properties and effectiveness. In this paper, we give an overview of properties of non-conformity score functions. We give examples of non-conformity score functions in the existing literature and introduce original modifications. We introduce an original method of evaluating the prediction set sizes of conformal predictors and use it to provide a comparison between non-conformity score functions. We also examine efficacy of different non-conformity score functions for class-conditional conformal prediction in a setting with imbalanced classes.

Sol Erika Boman, Nita Mulliqi, Anders Blilie et al.

Tissue detection is a crucial first step in most digital pathology applications. Details of the segmentation algorithm are rarely reported, and there is a lack of studies investigating the downstream effects of a poor segmentation algorithm. Disregarding tissue detection quality could create a bottleneck for downstream performance and jeopardize patient safety if diagnostically relevant parts of the specimen are excluded from analysis in clinical applications. This study aims to determine whether performance of downstream tasks is sensitive to the tissue detection method, and to compare performance of classical and AI-based tissue detection. To this end, we trained an AI model for Gleason grading of prostate cancer in whole slide images (WSIs) using two different tissue detection algorithms: thresholding (classical) and UNet++ (AI). A total of 33,823 WSIs scanned on five digital pathology scanners were used to train the tissue detection AI model. The downstream Gleason grading algorithm was trained and tested using 70,524 WSIs from 13 clinical sites scanned on 13 different scanners. There was a decrease from 116 (0.43%) to 22 (0.08%) fully undetected tissue samples when switching from thresholding-based tissue detection to AI-based, suggesting an AI model may be more reliable than a classical model for avoiding total failures on slides with unusual appearance. On the slides where tissue could be detected by both algorithms, no significant difference in overall Gleason grading performance was observed. However, tissue detection dependent clinically significant variations in AI grading were observed in 3.5% of malignant slides, highlighting the importance of robust tissue detection for optimal clinical performance of diagnostic AI.

Andrea Camilloni, Chiara Micoli, Nita Mulliqi et al.

Biochemical recurrence (BCR) after radical prostatectomy (RP) is a surrogate marker for aggressive prostate cancer with adverse outcomes, yet current prognostic tools remain imprecise. We trained an AI-based model on diagnostic prostate biopsy slides from the STHLM3 cohort (n = 676) to predict patient-specific risk of BCR, using foundation models and attention-based multiple instance learning. Generalizability was assessed across three external RP cohorts: LEOPARD (n = 508), CHIMERA (n = 95), and TCGA-PRAD (n = 379). The image-based approach achieved 5-year time-dependent AUCs of 0.64, 0.70, and 0.70, respectively. Integrating clinical variables added complementary prognostic value and enabled statistically significant risk stratification. Compared with guideline-based CAPRA-S, AI incrementally improved postoperative prognostication. These findings suggest biopsy-trained histopathology AI can generalize across specimen types to support preoperative and postoperative decision making, but the added value of AI-based multimodal approaches over simpler predictive models should be critically scrutinized in further studies.

Anders Blilie, Nita Mulliqi, Xiaoyi Ji et al.

Prostate cancer diagnosis heavily relies on histopathological evaluation, which is subject to variability. While immunohistochemical staining (IHC) assists in distinguishing benign from malignant tissue, it involves increased work, higher costs, and diagnostic delays. Artificial intelligence (AI) presents a promising solution to reduce reliance on IHC by accurately classifying atypical glands and borderline morphologies in hematoxylin & eosin (H&E) stained tissue sections. In this study, we evaluated an AI model's ability to minimize IHC use without compromising diagnostic accuracy by retrospectively analyzing prostate core needle biopsies from routine diagnostics at three different pathology sites. These cohorts were composed exclusively of difficult cases where the diagnosing pathologists required IHC to finalize the diagnosis. The AI model demonstrated area under the curve values of 0.951-0.993 for detecting cancer in routine H&E-stained slides. Applying sensitivity-prioritized diagnostic thresholds reduced the need for IHC staining by 44.4%, 42.0%, and 20.7% in the three cohorts investigated, without a single false negative prediction. This AI model shows potential for optimizing IHC use, streamlining decision-making in prostate pathology, and alleviating resource burdens.