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Heterogeneity in Genomic Risk Assessment from Tissue Based Prognostic Signatures Used in the Biopsy Setting and the Impact of Magnetic Resonance Imaging Targeted Biopsy.基于组织的活检预后标志物的基因组风险评估中的异质性和磁共振成像靶向活检的影响。
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评估前列腺癌活检采样的分子异质性:来自MAST试验的见解。

Assessing the Molecular Heterogeneity of Prostate Cancer Biopsy Sampling: Insights from the MAST Trial.

作者信息

Ajami Tarek, Yu Hui, Porto Joao G, Prakash Nachiketh Soodana, Williams Adam, Avda Yuval, Malpani Ankur, Mendiola Dinno F, Freitas Pedro F S, Khandekar Archan, Swain Sanjaya, Gaston Sandra, Mahal Brandon, Cortizas Elena, Szczotka Zoe, Gerard Timothy, Kava Bruce, Stoyanova Radka, Kryvenko Oleksandr N, Castillo Patricia, Ritch Chad R, Nahar Bruno, Gonzalgo Mark L, Pollack Alan, Parekh Dipen J, Punnen Sanoj

机构信息

Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, FL, USA; Department and Laboratory of Urology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain.

Department of Public Health Sciences, Sylvester Comprehensive Cancer Center, Miami, FL, USA.

出版信息

Eur Urol Focus. 2024 Dec 10. doi: 10.1016/j.euf.2024.11.012.

DOI:10.1016/j.euf.2024.11.012
PMID:39665894
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12149333/
Abstract

BACKGROUND AND OBJECTIVE

Prostate cancer (PC) heterogeneity can result in sampling discrepancies during biopsy, leading to inaccurate molecular classifications that affect treatment decisions. We evaluated transcriptomic profile variability between multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy (TBx) and systematic biopsy (SBx) methods using the Decipher GRID platform.

METHODS

The study included 205 men from the MAST trial. We analyzed 408 biopsy samples, of which 149 were TBx and 259 were SBx samples. Three prognostic signatures-the Decipher genomic classifier (DGC), cell cycle progression (CCP), and Genomic Prostate Score-were assessed in relation to grade group (GG) and MRI phenotype. Multivariable linear regression was conducted to adjust for the confounding effects of GG and tumor purity.

KEY FINDINGS AND LIMITATIONS

Unpaired analysis revealed that TBx samples had higher derived GPS and CCP scores than SBx samples (p < 0.05), but the difference was no longer significant after multiple-test adjustment. There was no significant difference in scores between SBx and TBx samples in the subgroup with GG 1 disease. For TBx cores, higher genomic scores were associated with higher Prostate Imaging-Reporting and Data System (PI-RADS) scores in the overall cohort, but not in the GG 1 subgroup. Multivariable analysis revealed significant associations between DGC and CCP scores and PI-RADS scores (p < 0.01). Higher DGC score concordance between TBx and SBx lesions was observed in the low-risk subgroup. A limitation of the study is the small sample size, so further validation is required.

CONCLUSIONS AND CLINICAL IMPLICATIONS

TBx samples yield higher genomic scores than SBx samples, with grade influencing the association between PI-RADS score and genomic risk. For the GG 1 subgroup, there was no correlation between PI-RADS and genomic scores. These findings need further validation to assess the impact of TBx on genomic risk assessment in active surveillance.

PATIENT SUMMARY

We examined the effectiveness of two different biopsy methods in assessing the risk of prostate cancer (PC) progression. We found that while biopsy samples guided by MRI (magnetic resonance imaging) scans often showed higher genetic risk scores than biopsy samples without MRI guidance, the difference was not significant for men with lower-grade PC. Our findings suggest that MRI targeting for biopsy might not always provide additional information about cancer aggressiveness for patients with low-risk PC.

摘要

背景与目的

前列腺癌(PC)的异质性可导致活检过程中的采样差异,从而产生影响治疗决策的不准确分子分类。我们使用Decipher GRID平台评估了多参数磁共振成像(mpMRI)靶向活检(TBx)和系统活检(SBx)方法之间的转录组谱变异性。

方法

该研究纳入了MAST试验中的205名男性。我们分析了408份活检样本,其中149份为TBx样本,259份为SBx样本。评估了三种预后特征——Decipher基因组分类器(DGC)、细胞周期进程(CCP)和基因组前列腺评分——与分级组(GG)和MRI表型的关系。进行多变量线性回归以调整GG和肿瘤纯度的混杂效应。

主要发现与局限性

非配对分析显示,TBx样本的衍生GPS和CCP评分高于SBx样本(p < 0.05),但在多重检验调整后差异不再显著。在GG 1疾病亚组中,SBx和TBx样本的评分没有显著差异。对于TBx核心样本,在整个队列中,较高的基因组评分与较高的前列腺影像报告和数据系统(PI-RADS)评分相关,但在GG 1亚组中并非如此。多变量分析显示DGC和CCP评分与PI-RADS评分之间存在显著关联(p < 0.01)。在低风险亚组中,观察到TBx和SBx病变之间的DGC评分一致性更高。该研究的一个局限性是样本量小,因此需要进一步验证。

结论与临床意义

TBx样本产生的基因组评分高于SBx样本,分级影响PI-RADS评分与基因组风险之间的关联。对于GG 1亚组,PI-RADS与基因组评分之间没有相关性。这些发现需要进一步验证,以评估TBx对主动监测中基因组风险评估的影响。

患者总结

我们研究了两种不同活检方法在评估前列腺癌(PC)进展风险方面的有效性。我们发现,虽然由MRI(磁共振成像)扫描引导的活检样本通常显示出比没有MRI引导的活检样本更高的遗传风险评分,但对于低级别PC患者,差异并不显著。我们的发现表明,对于低风险PC患者,MRI靶向活检可能并不总是能提供有关癌症侵袭性的额外信息。