Race-specific trajectories of prostate cancer evolution: Distinct temporal and spatial progression patterns in African American and Caucasian men

African American (AA) men experience a higher incidence and mortality from prostate cancer, traditionally attributed to more aggressive tumor biology. However, emerging evidence suggests that when access to care is equal, AA men often have outcomes comparable to-or better than-Caucasian men, showing that biological behavior may be distinct rather than inherently worse. To clarify early evolutionary trajectories, we performed a detailed race-stratified analysis of temporal and spatial progression patterns using serial 12-core and saturation biopsies.Longitudinal biopsy datasets were evaluated to measure time-to-progression across key histologic transitions from benign to HGPIN, benign to high-grade Gleason patterns, and within-grade upgrading. Site-specific progression proportions were compared across 12 anatomical regions. Statistical significance for temporal and spatial differences was assessed using proper parametric tests.In 12-core biopsies, AA men showed significantly slower progression from benign tissue to Gleason 5+5 carcinoma (140.77 vs. 8.49 months; p<0.0001) and a trend toward delayed progression from benign to HGPIN (p=0.051). In contrast, AA men showed faster progression from Gleason 3+4 to 4+3 (15.84 vs. 42.37 months; p = 0.0005), exhibiting a distinct-not uniformly aggressive-pattern of disease evolution. Spatial mapping showed higher progression rates in Caucasian men at the right lateral base and apical regions. In contrast, AA men showed greater progression in the left-sided areas (left base, lateral base, mid, and lateral mid).In saturation biopsies, AA men again displayed slower transitions from benign to Gleason 3+3 (22.36 vs. 18.35 months; p=0.073), benign to Gleason 4+4 (24.1 vs. 15.14 months; p=0.021), and from Gleason 3+3 to 3+4 (21.29 vs. 14.05 months; p=0.021). Anatomically, Caucasian men showed higher progression at the left lateral base, while AA men showed higher progression at the right lateral base.Our serial biopsy analyses reveal that AA men experience slower early biological progression from benign and low-grade disease compared to Caucasian men, challenging the long-standing assumption that AA prostate cancer is intrinsically more aggressive. Instead, these findings support a model of biologically distinct evolutionary pathways, with AA men exhibiting delayed early transitions but accelerated intermediate-grade shifts, and displaying unique spatial patterns of progression. These results align with recent clinical and genomic studies showing equal or better outcomes for AA men when access to care is equivalent. Collectively, our findings offer mechanistic insight into race-specific prostate cancer evolution and underscore the need for tailored surveillance and sampling strategies.