Genomic Classifier for Guiding Treatment of Intermediate-Risk Prostate Cancers to Dose-Escalated Image Guided Radiation Therapy Without Hormone Therapy
Genomic Classifier for Guiding Treatment of Intermediate-Risk Prostate Cancers to Dose-Escalated Image Guided Radiation Therapy Without Hormone Therapy
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DOI：
10.1016/j.ijrobp.2018.08.030
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发表时间：
2019-01-01
影响因子：
7
通讯作者：
Chua, Melvin L. K.
中科院分区：
文献类型：
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作者：
Berlin, Alejandro;Murgic, Jure;Chua, Melvin L. K.
目的：美国国家综合癌症网络（NCCN）最近支持将中危前列腺癌（IR-PCa）分为有利和不利亚组，并建议在不利IR-PCa的放射治疗（RT）中添加雄激素剥夺治疗（ADT）。最近，通过将22个特征的基因组分类器（GC）整合到NCCN分层系统中，证明了更准确的分类。在这里，我们测试的GC的效用，以更好地确定患者IR-PCa谁是充分的RT单独治疗。方法和材料：我们确定了一个新的队列，包括121例患者IRP-Ca治疗剂量递增的图像引导RT（78戈伊，39个分数）没有ADT。GC评分来源于诊断性活检中取样的肿瘤。多变量分析，包括NCCN亚分类和GC评分，进行生化失败（前列腺特异性抗原最低峰2 ng/mL）和转移occupation.Results：通过NCCN亚分类，33（27.3%）和87（71.9%）的男性被归类为有利和不利的IR-PCa，分别（1例无法分类）。GC评分在3例有利的IR-PCa中较高，在60例不利的IR-PCa中较低。较高的GC评分，而非NCCN风险亚组，与生化复发（风险比，1.36; 95%置信区间[CI]，1.09-1.71]每增加10%; P = 0.007）和转移（风险比，2.05; 95% CI，1.24-4.24; P = 0.004）相关。GC预测5年时生化失败（曲线下面积，0.78; 95%CI，0.59-0.91），并且组合NCCN棘状GC模型在预测早发性转移方面显著优于单独NCCN模型。（5年转移曲线下面积为0.89 vs 0.86 [单独GC] vs 0.54 [单独NCCN]）。我们证明了GC预测单独使用剂量递增的图像引导RT治疗的IR-PCa疾病复发的准确性。我们的研究结果强调，需要在一项前瞻性临床试验中评估这种GC，该试验旨在研究ADT-RT在临床基因组学定义的IR-PCa亚组中的作用。(C)2018由Elsevier Inc.出版
Purpose: The National Comprehensive Cancer Network (NCCN) has recently endorsed the stratification of intermediate-risk prostate cancer (IR-PCa) into favorable and unfavorable subgroups and recommend the addition of androgen deprivation therapy (ADT) to radiation therapy (RT) for unfavorable IR-PCa. Recently, more accurate prognostication was demonstrated by integrating a 22-feature genomic classifier (GC) to the NCCN stratification system. Here, we test the utility of the GC to better identify patients with IR-PCa who are sufficiently treated by RT alone.Methods and Materials: We identified a novel cohort comprising 121 patients with IRP-Ca treated with dose-escalated image guided RT (78 Gy in 39 fractions) without ADT. GC scores were derived from tumors sampled in diagnostic biopsies. Multivariable analyses, including both NCCN subclassification and GC scores, were performed for biochemical failure (prostate-specific antigen nadir thorn 2 ng/mL) and metastasis occurrence.Results: By NCCN subclassification, 33 (27.3%) and 87 (71.9%) of men were classified as having favorable and unfavorable IR-PCa, respectively (1 case unclassifiable). GC scores were high in 3 favorable IR-PCa and low in 60 unfavorable IR-PCa. Higher GC scores, but not NCCN risk subgroups, were associated with biochemical relapse (hazard ratio, 1.36; 95% confidence interval [CI], 1.09-1.71] per 10% increase; P = .007) and metastasis (hazard ratio, 2.05; 95% CI, 1.24-4.24; P = .004). GC predicted biochemical failure at 5 years (area under the curve, 0.78; 95% CI, 0.59-0.91), and the combinatorial NCCN thorn GC model significantly outperformed the NCCN alone model for predicting early-onset metastasis (area under the curve for 5-year metastasis of 0.89 vs 0.86 [GC alone] vs 0.54 [NCCN alone]).Conclusions: We demonstrated the accuracy of the GC for predicting disease recurrence in IR-PCa treated with dose-escalated image guided RT alone. Our findings highlight the need to evaluate this GC in a prospective clinical trial investigating the role of ADT-RT in clinicogenomic-defined IR-PCa subgroups. (C) 2018 Published by Elsevier Inc.