PO.PR01.01 · 预防研究
前列腺癌演进的种族特异性轨迹:非裔美国男性与高加索男性中不同的时间和空间进展模式
Race-specific trajectories of prostate cancer evolution: Distinct temporal and spatial progression patterns in African American and Caucasian men
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摘要 Abstract
中文摘要
非裔美国(AA)男性的前列腺癌发病率和死亡率较高,传统上归因于更具侵袭性的肿瘤生物学。然而,新出现的证据提示,当医疗可及性平等时,AA男性的结局往往与高加索男性相当甚至更好,表明其生物学行为可能是独特的,而非本质上更差。为阐明早期演进轨迹,我们利用连续的12针和饱和穿刺活检,对时间和空间进展模式进行了详细的种族分层分析。评估了纵向活检数据集,以测量从良性到HGPIN、良性到高级别Gleason模式以及级别内升级等关键组织学转变的进展时间。在12个解剖区域间比较了部位特异性进展比例。使用适当的参数检验评估了时间和空间差异的统计学显著性。在12针活检中,AA男性从良性组织到Gleason 5+5癌的进展显著更慢(140.77 vs. 8.49个月;p < 0.0001),并呈现从良性到HGPIN进展延迟的趋势(p = 0.051)。相反,AA男性从Gleason 3+4到4+3的进展更快(15.84 vs. 42.37个月;p = 0.0005),呈现出一种独特的、并非一律侵袭性的疾病演进模式。空间制图显示高加索男性在右侧外侧底部和尖部区域的进展率更高。相反,AA男性在左侧区域(左底部、外侧底部、中部和外侧中部)进展更多。在饱和活检中,AA男性再次表现出从良性到Gleason 3+3(22.36 vs. 18.35个月;p = 0.073)、良性到Gleason 4+4(24.1 vs. 15.14个月;p = 0.021)以及从Gleason 3+3到3+4(21.29 vs. 14.05个月;p = 0.021)的更慢转变。在解剖学上,高加索男性在左外侧底部进展更高,而AA男性在右外侧底部进展更高。我们的连续活检分析揭示,与高加索男性相比,AA男性从良性和低级别疾病经历更慢的早期生物学进展,挑战了长期以来认为AA前列腺癌本质上更具侵袭性的假设。相反,这些发现支持一种生物学上不同的演进途径模型,AA男性表现出早期转变延迟但中级别转移加速,并展现出独特的进展空间模式。这些结果与近期临床和基因组研究一致,后者显示当医疗可及性平等时AA男性有相当或更好的结局。总体而言,我们的发现为种族特异性前列腺癌演进提供了机制性见解,并强调了对量身定制的监测和取样策略的需求。
查看英文原文 English abstract
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.
利益披露 Disclosure
J. Harsh, None..
S. Carskadon, None..
N. S. Gupta, None..
S. Jyothilingam, None..
J. Ryba, None..
C. G. Rogers, None..
J. O. Peabody, None..
S. Ghosh, None..
N. Palanisamy, None.