Charting the unseen: 3D mapping of latent prostate cancer infers its likely origin and growth patterns

Latent prostate cancers discovered at autopsy may represent the earliest, subclinical stage of the disease. This study aimed to construct three-dimensional (3D) spatial distribution maps of these tumors to infer their likely origin and growth patterns.

A total of 161 tumor lesions from 230 cadaver donors were stratified by volume (V1: 0-0.05 ml; V2: 0.05-0.1 ml; V3: 0.1-0.5 ml; V4: > 0.5 ml) and registered to a standardized MRI-based reference prostate model using Advanced Normalization Tools. Two-dimensional frequency maps were generated per axial layer and stacked into a 3D map.

The smallest tumors (V1) originated almost exclusively in the peripheral zone (83.5%), concentrated in the apical two-thirds of the gland (95.9%), with a uniform distribution across the anterior-posterior and left-right axes. As tumor volume increased (V2 to V4), three distinct growth patterns emerged: (1) increased invasion into the transition zone; (2) horizontal convergence into three "hotspots"-the anterior midline and bilateral posterolateral regions; and (3) vertical concentration within layers III to IX. A compact "susceptible region" occupying only 9.8% of the gland volume harbored 88.2% of the largest (V4) tumors.

Latent prostate cancers appear to originate predominantly within the apical-to-mid peripheral zone with an initially uniform spatial distribution. Their growth is anisotropic, favoring the anterior midline and bilateral posterolateral zones while concentrating vertically within the central 20-40% of the prostatic height. These spatial patterns point to target areas that may improve biopsy strategies and focal therapy planning.