Causal-Adversarial Probing of Clinical Covariates for Prostate MRI Grading

Yipei Wang, Shiqi Huang, Wen Yan, Weixi Yi, Dean C. Barratt, Mark Emberton, Daniel C. Alexander, Veeru Kasivisvanathan, Yipeng Hu

Deep learning models for prostate MRI-based cancer grading may encode clinical covariates that either reflect useful disease-related signal or non-generalising shortcut information, but their role is usually assumed. We propose a causal-reasoning framework for probing covariate dependence in MRI-based International Society of Urological Pathology (ISUP) Grade Group prediction. Rather than treating mpMRI as a direct cause of grade, we model MRI appearance and ISUP grade as observations of latent tumour pathology, and test whether candidate clinical variables act as nuisance correlates, disease-related proxies, or irrelevant covariates in the learned representation. We implement this using an adversarial framework that suppresses the decodability of individual clinical covariate at a time while preserving MRI-based grade prediction. The approach is developed and evaluated on 2,903 prostate MRI examinations, with external validation on 576 patients. We report a set of interesting and previously under-explored imaging-to-clinical-variable interactions in the context of deep learning generalisation. For examples, in binary ISUP Grade Group $\geq2$ classification, suppressing age, BMI, and alcohol use improved AUC by 1.23%, 0.84%, and 1.42%, respectively (all p < 0.05), suggesting reduced non-generalising covariate information; In contrast, suppressing PSA and prostate volume degraded AUC by 1.91% and 7.61% (all p < 0.001), indicating that these variables carried task-relevant signal. These findings show that adversarial covariate suppression can provide a practical representation-level analysis for distinguishing potentially harmful dependence from informative signal in prostate MRI grading models.