Extracting and analyzing 3D histomorphometric features related to perineural and lymphovascular invasion in prostate cancer

Minimizing invasive diagnostic procedures to reduce the risk of patient injury and infection is a central goal in medical imaging. And yet, noninvasive diagnosis of perineural invasion (PNI), a critical prognostic factor involving infiltration of tumor cells along the surrounding nerve, still remains challenging, due to the lack of clear and consistent imaging criteria criteria for identifying PNI. To address this challenge, we present NeoNet, an integrated end-to-end 3D deep learning framework for PNI prediction in cholangiocarcinoma that does not rely on predefined image features. NeoNet integrates three modules: (1) NeoSeg, utilizing a Tumor-Localized ROI Crop (TLCR) algorithm; (2) NeoGen, a 3D Latent Diffusion Model (LDM) with ControlNet, conditioned on anatomical masks to generate synthetic image patches, specifically balancing the dataset to a 1:1 ratio; and (3) NeoCls, the final prediction module. For NeoCls, we developed the PNI-Attention Network (PattenNet), which uses the frozen LDM encoder and specialized 3D Dual Attention Blocks (DAB) designed to detect subtle intensity variations and spatial patterns indicative of PNI. In 5-fold cross-validation, NeoNet outperformed baseline 3D models and achieved the highest performance with a maximum AUC of 0.7903.

Perineural invasion (PNI) is a clinically relevant indicator of tumor aggressiveness and can influence surgical decision-making, motivating interest in reliable preoperative assessment. The subtle MRI features of PNI, however, often resemble nearby anatomy, complicating noninvasive prediction. These fine perineural cues are easily attenuated by routine downsampling or overly global feature aggregation, reducing the effectiveness of conventional volumetric models. We present LoSA-Net, a localized and scale-adaptive architecture for boundary-sensitive PNI prediction in 3D MRI. Talking Neighborhood Attention (TNA) preserves nerve-aligned detail through localized self-attention with head-wise mixing, and Scale-Adaptive Feature Mixing (SAFM) modulates the receptive field using multi-scale depthwise processing. Cross-Scale Refinement and Alignment (CSRA) maintains consistency between semantic context and high-resolution boundaries across stages. In contrast-enhanced MRI scans from 168 patients with cholangiocarcinoma, LoSA-Net achieves an AUC of 0.7567 and outperforms representative convolutional and transformer baselines under matched preprocessing and optimization settings.

Accurate prediction of biochemical recurrence (BCR) after radical prostatectomy is critical for guiding adjuvant treatment and surveillance decisions in prostate cancer. However, existing clinicopathological risk models reduce complex morphology to relatively coarse descriptors, leaving substantial prognostic information embedded in routine histopathology underexplored. We present a deep learning-based biomarker that predicts continuous, patient-specific risk of BCR directly from H&E-stained whole-slide prostatectomy specimens. Trained end-to-end on time-to-event outcomes and evaluated across four independent international cohorts, our model demonstrates robust generalization across institutions and patient populations. When integrated with the CAPRA-S clinical risk score, the deep learning risk score consistently improved discrimination for BCR, increasing concordance indices from 0.725-0.772 to 0.749-0.788 across cohorts. To support clinical interpretability, outcome-grounded analyses revealed subtle histomorphological patterns associated with recurrence risk that are not captured by conventional clinicopathological risk scores. This multicohort study demonstrates that deep learning applied to routine prostate histopathology can deliver reproducible and clinically generalizable biomarkers that augment postoperative risk stratification, with potential to support personalized management of prostate cancer in real-world clinical settings.