Tobias Nordström

Tim Nikolass Lindeijer, Tord Martin Ytredal, Trygve Eftestøl et al.

An accurate prostate delineation and volume characterization can support the clinical assessment of prostate cancer. A large amount of automatic prostate segmentation tools consider exclusively the axial MRI direction in spite of the availability as per acquisition protocols of multi-view data. Further, when multi-view data is exploited, manual annotations and availability at test time for all the views is commonly assumed. In this work, we explore a contrastive approach at training time to leverage multi-view data without annotations and provide flexibility at deployment time in the event of missing views. We propose a triplet encoder and single decoder network based on U-Net, tU-Net (triplet U-Net). Our proposed architecture is able to exploit non-annotated sagittal and coronal views via contrastive learning to improve the segmentation from a volumetric perspective. For that purpose, we introduce the concept of inter-view similarity in the latent space. To guide the training, we combine a dice score loss calculated with respect to the axial view and its manual annotations together with a multi-view contrastive loss. tU-Net shows statistical improvement in dice score coefficient (DSC) with respect to only axial view (91.25+-0.52% compared to 86.40+-1.50%,P<.001). Sensitivity analysis reveals the volumetric positive impact of the contrastive loss when paired with tU-Net (2.85+-1.34% compared to 3.81+-1.88%,P<.001). Further, our approach shows good external volumetric generalization in an in-house dataset when tested with multi-view data (2.76+-1.89% compared to 3.92+-3.31%,P=.002), showing the feasibility of exploiting non-annotated multi-view data through contrastive learning whilst providing flexibility at deployment in the event of missing views.

Alvaro Fernandez-Quilez, Tobias Nordström, Fredrik Jäderling et al.

Background: Prostate cancer (PC) MRI-based risk calculators are commonly based on biological (e.g. PSA), MRI markers (e.g. volume), and patient age. Whilst patient age measures the amount of years an individual has existed, biological age (BA) might better reflect the physiology of an individual. However, surrogates from prostate MRI and linkage with clinically significant PC (csPC) remain to be explored. Purpose: To obtain and evaluate Prostate Age Gap (PAG) as an MRI marker tool for csPC risk. Study type: Retrospective. Population: A total of 7243 prostate MRI slices from 468 participants who had undergone prostate biopsies. A deep learning model was trained on 3223 MRI slices cropped around the gland from 81 low-grade PC (ncsPC, Gleason score <=6) and 131 negative cases and tested on the remaining 256 participants. Assessment: Chronological age was defined as the age of the participant at the time of the visit and used to train the deep learning model to predict the age of the patient. Following, we obtained PAG, defined as the model predicted age minus the patient's chronological age. Multivariate logistic regression models were used to estimate the association through odds ratio (OR) and predictive value of PAG and compared against PSA levels and PI-RADS>=3. Statistical tests: T-test, Mann-Whitney U test, Permutation test and ROC curve analysis. Results: The multivariate adjusted model showed a significant difference in the odds of clinically significant PC (csPC, Gleason score >=7) (OR =3.78, 95% confidence interval (CI):2.32-6.16, P <.001). PAG showed a better predictive ability when compared to PI-RADS>=3 and adjusted by other risk factors, including PSA levels: AUC =0.981 vs AUC =0.704, p<.001. Conclusion: PAG was significantly associated with the risk of clinically significant PC and outperformed other well-established PC risk factors.

Erlend Sortland Rolfsnes, Philip Thangngat, Trygve Eftestøl et al.

Artificial intelligence systems show promise to aid in the di- agnostic pathway of prostate cancer (PC), by supporting radiologists in interpreting magnetic resonance images (MRI) of the prostate. Most MRI-based systems are designed to detect clinically significant PC le- sions, with the main objective of preventing over-diagnosis. Typically, these systems involve an automatic prostate segmentation component and a clinically significant PC lesion detection component. In spite of the compound nature of the systems, evaluations are presented assum- ing a standalone clinically significant PC detection component. That is, they are evaluated in an idealized scenario and under the assumption that a highly accurate prostate segmentation is available at test time. In this work, we aim to evaluate a clinically significant PC lesion de- tection system accounting for its compound nature. For that purpose, we simulate a realistic deployment scenario and evaluate the effect of two non-ideal and previously validated prostate segmentation modules on the PC detection ability of the compound system. Following, we com- pare them with an idealized setting, where prostate segmentations are assumed to have no faults. We observe significant differences in the de- tection ability of the compound system in a realistic scenario and in the presence of the highest-performing prostate segmentation module (DSC: 90.07+-0.74), when compared to the idealized one (AUC: 77.93 +- 3.06 and 84.30+- 4.07, P<.001). Our results depict the relevance of holistic evalu- ations for PC detection compound systems, where interactions between system components can lead to decreased performance and degradation at deployment time.

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.

Anindo Saha, Joeran S. Bosma, Jasper J. Twilt et al.

In this intercontinental, confirmatory study, we include a retrospective cohort of 22,481 MRI examinations (21,288 patients; 46 cities in 22 countries) to train and externally validate the PI-CAI-2B model, i.e., an efficient, next-generation iteration of the state-of-the-art AI system that was developed for detecting Gleason grade group $\geq$2 prostate cancer on MRI during the PI-CAI study. Of these examinations, 20,471 cases (19,278 patients; 26 cities in 14 countries) from two EU Horizon projects (ProCAncer-I, COMFORT) and 12 independent centers based in Europe, North America, Asia and Africa, are used for training and internal testing. Additionally, 2010 cases (2010 patients; 20 external cities in 12 countries) from population-based screening (STHLM3-MRI, IP1-PROSTAGRAM trials) and primary diagnostic settings (PRIME trial) based in Europe, North and South Americas, Asia and Australia, are used for external testing. Primary endpoint is the proportion of AI-based assessments in agreement with the standard of care diagnoses (i.e., clinical assessments made by expert uropathologists on histopathology, if available, or at least two expert urogenital radiologists in consensus; with access to patient history and peer consultation) in the detection of Gleason grade group $\geq$2 prostate cancer within the external testing cohorts. Our statistical analysis plan is prespecified with a hypothesis of diagnostic interchangeability to the standard of care at the PI-RADS $\geq$3 (primary diagnosis) or $\geq$4 (screening) cut-off, considering an absolute margin of 0.05 and reader estimates derived from the PI-CAI observer study (62 radiologists reading 400 cases). Secondary measures comprise the area under the receiver operating characteristic curve (AUROC) of the AI system stratified by imaging quality, patient age and patient ethnicity to identify underlying biases (if any).