Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA, USA.
Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
Eur Urol. 2021 Jan;79(1):141-149. doi: 10.1016/j.eururo.2020.09.003. Epub 2020 Nov 2.
Distinguishing indolent from aggressive prostate cancer remains a key challenge for decision making regarding prostate cancer management. A growing number of biomarkers are now available to help address this need, but these have rarely been examined together in the same patients to determine their potentially additive value.
To determine whether two previously validated plasma markers (transforming growth factor β1 [TGFβ1] and interleukin-6 soluble receptor [IL6-SR]) and two validated tissue scores (the Genomic Evaluators of Metastatic Prostate Cancer [GEMCaP] and cell cycle progression [CCP] scores) can improve on clinical parameters in predicting adverse pathology after prostatectomy, and how much they vary within tumors with heterogeneous Gleason grade.
DESIGN, SETTING, AND PARTICIPANTS: A case-control study was conducted among men with low-risk cancers defined by biopsy grade group (GG) 1, prostate-specific antigen (PSA) ≤10 ng/mL, and clinical stage ≤ T2 who underwent immediate prostatectomy. We collected paraffin-fixed prostatectomy tissue and presurgical plasma samples from 381 cases from the University of California, San Francisco, and 260 cases from the University of Washington.
Pathologic outcomes were minor upgrading/upstaging (GG 2 or pT3a) or major upgrading/upstaging (GG ≥ 3 or ≥ pT3b), and multinomial regression was performed to determine putative markers' ability to predict these outcomes, controlling for PSA, percent of positive biopsy cores, age, and clinical site. For upgraded tumors, a secondary analysis of the GEMCaP and CCP scores from the higher-grade tumor was also performed to evaluate for heterogeneity.
Overall, 357 men had no upgrading/upstaging event at prostatectomy, 236 had a minor event, and 67 had a major event. Neither TGFβ1 nor IL6-SR was statistically significantly associated with any upgrading/upstaging. On the contrary, both the CCP and the GEMCaP score obtained from Gleason pattern 3 tissue were directly associated with minor and major upgrading/upstaging on univariate analysis. The two scores correlated with each other, but weakly. On multinomial analysis including both scores in the model, the CCP score predicted minor upgrading/upstaging (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.05-2.49) and major upgrading/upstaging (OR 2.26, 95% CI 1.05-4.90), p = 0.04), and the GEMCaP score also predicted minor upgrading/upstaging (OR 1.05, 95% CI 1.03-1.08) and major upgrading/upstaging (OR 1.07, 95% CI 1.04-1.11), p < 0.01). The other clinical parameters were not significant in this model. Among upgraded tumors including both Gleason patterns 3 and 4, both the GEMCaP and the CCP score tended to be higher from the higher-grade tumor. The main limitation was the use of virtual biopsies from prostatectomy tissue as surrogates for prostate biopsies.
Biomarker signatures based on analyses of both DNA and RNA significantly and independently predict adverse pathology among men with clinically low-risk prostate cancer undergoing prostatectomy.
Validated biomarker scores derived from both prostate cancer DNA and prostate cancer RNA can add independent information to help predict outcomes after prostatectomy.
在决定前列腺癌管理方案时，区分惰性和侵袭性前列腺癌仍然是一个关键挑战。现在有越来越多的生物标志物可用于帮助满足这一需求，但这些标志物很少在同一患者中一起进行检查，以确定它们潜在的附加价值。
确定两个先前经过验证的血浆标志物（转化生长因子β 1[TGFβ1]和白细胞介素 6 可溶性受体[IL6-SR]）和两个经过验证的组织评分（基因组转移性前列腺癌评估者[GEMCaP]和细胞周期进展[CCP]评分）是否可以改善前列腺切除术后不良病理的预测，并确定它们在具有异质性 Gleason 分级的肿瘤内有多大差异。
设计、地点和参与者：这项病例对照研究在低风险癌症患者中进行，定义为活检分级组（GG）1、前列腺特异性抗原（PSA）≤10ng/mL 和临床分期≤T2 的患者，他们接受了即刻前列腺切除术。我们从加利福尼亚大学旧金山分校收集了 381 例患者的石蜡固定前列腺切除术组织和术前血浆样本，从华盛顿大学收集了 260 例患者的石蜡固定前列腺切除术组织和术前血浆样本。
病理结局为轻微升级/升级（GG 2 或 pT3a）或主要升级/升级（GG≥3 或≥pT3b），采用多项回归分析确定潜在标志物预测这些结局的能力，控制 PSA、阳性活检核心百分比、年龄和临床部位。对于升级的肿瘤，还对来自高级别肿瘤的 GEMCaP 和 CCP 评分进行了二次分析，以评估异质性。
总体而言，357 名患者在前列腺切除术后无升级/升级事件，236 名患者有轻微事件，67 名患者有主要事件。TGFβ1 和 IL6-SR 均与任何升级/升级均无统计学显著相关性。相反，在单变量分析中，来自 Gleason 模式 3 组织的 CCP 和 GEMCaP 评分均与轻微和主要升级/升级直接相关。两个评分相互关联，但相关性较弱。在包括模型中两个评分的多项分析中，CCP 评分预测轻微升级/升级（优势比[OR]1.62，95%置信区间[CI]1.05-2.49）和主要升级/升级（OR 2.26，95%CI 1.05-4.90），p=0.04），GEMCaP 评分也预测轻微升级/升级（OR 1.05，95%CI 1.03-1.08）和主要升级/升级（OR 1.07，95%CI 1.04-1.11），p<0.01）。该模型中的其他临床参数没有意义。在包括 Gleason 模式 3 和 4 的升级肿瘤中，来自高级别肿瘤的 GEMCaP 和 CCP 评分往往更高。主要限制是使用前列腺切除术组织的虚拟活检作为前列腺活检的替代品。
基于 DNA 和 RNA 分析的生物标志物特征可显著且独立地预测接受前列腺切除术的临床低危前列腺癌患者的不良病理。
源自前列腺癌 DNA 和前列腺癌 RNA 的验证生物标志物评分可提供独立信息，有助于预测前列腺切除术后的结果。
