Beyond Radiomics Alone: Enhancing Prostate Cancer Classification with ADC Ratio in a Multicenter Benchmarking Study

<b>Background/Objectives</b>: Radiomics enables extraction of quantitative imaging features to support non-invasive classification of prostate cancer (PCa). Accurate detection of clinically significant PCa (csPCa; Gleason score ≥ 3 + 4) is crucial for guiding treatment decisions. However, many studies explore limited feature selection, classifier, and harmonization combinations, and lack external validation. We aimed to systematically benchmark modeling pipelines and evaluate whether combining radiomics with the lesion-to-normal ADC ratio improves classification robustness and generalizability in multicenter datasets. <b>Methods</b>: Radiomic features were extracted from ADC maps using IBSI-compliant pipelines. Over 100 model configurations were tested, combining eight feature selection methods, fifteen classifiers, and two harmonization strategies across two scenarios: (1) repeated cross-validation on a multicenter dataset and (2) nested cross-validation with external testing on the PROSTATEx dataset. The ADC ratio was defined as the mean lesion ADC divided by contralateral normal tissue ADC, by placing two identical ROIs in each side, enabling patient-specific normalization. <b>Results</b>: In Scenario 1, the best model combined radiomics, ADC ratio, LASSO, and Naïve Bayes (AUC-PR = 0.844 ± 0.040). In Scenario 2, the top-performing configuration used Recursive Feature Elimination (RFE) and Boosted GLM (a generalized linear model trained with boosting), generalizing well to the external set (AUC-PR = 0.722; F1 = 0.741). ComBat harmonization improved calibration but not external discrimination. Frequently selected features were texture-based (GLCM, GLSZM) from wavelet- and LoG-filtered ADC maps. <b>Conclusions</b>: Integrating radiomics with the ADC ratio improves csPCa classification and enhances generalizability, supporting its potential role as a robust, clinically interpretable imaging biomarker in multicenter MRI studies.