Abstract：
OBJECTIVE: To evaluate the utility of the 17-gene Genomic Prostate Score® (GPS; MDxHealth, Irvine, CA, USA) performed on prostate cancer at the positive margin of the radical prostatectomy (RP) for its association with risk of subsequent biochemical recurrence (BCR).
METHODS: We designed a case-cohort for the outcome of BCR, selecting 223 from a cohort of 813 RP patients treated at Johns Hopkins from 2008 to 2017 with positive margins and available clinical data; of these, 213 had available tissue and clinical data. RNA was isolated from formalin-fixed paraffin-embedded tumour tissue adjacent to the positive surgical margin and the GPS was evaluable in 203 of these patients with a score ranging from 0 to 100, with higher scores indicating higher risk. All patients underwent RP with or without adjuvant radiation therapy (ART). The statistical analysis employed Cox proportional hazards regression models for outcome of BCR weighted for case-cohort design.
RESULTS: In univariable analysis, every 20-unit increase in the GPS was associated with a nearly threefold increase in risk of BCR (hazard ratio [HR] per 20 units 2.82, P < 0.001). In a multivariable Cox model adjusted for age, race, Cancer of the Prostate Risk Assessment Postsurgical score, Grade Group at the positive margin, and ART, the GPS was significantly associated with BCR (HR 1.56 per 20 units; 95% confidence interval 1.11-2.19; P = 0.011). The study is limited by its retrospective and single institution design.
CONCLUSIONS: The GPS at the positive surgical margin could help stratify prognosis and inform clinical decision-making regarding adjuvant therapy after RP.
METHODS: We designed a case-cohort for the outcome of BCR, selecting 223 from a cohort of 813 RP patients treated at Johns Hopkins from 2008 to 2017 with positive margins and available clinical data; of these, 213 had available tissue and clinical data. RNA was isolated from formalin-fixed paraffin-embedded tumour tissue adjacent to the positive surgical margin and the GPS was evaluable in 203 of these patients with a score ranging from 0 to 100, with higher scores indicating higher risk. All patients underwent RP with or without adjuvant radiation therapy (ART). The statistical analysis employed Cox proportional hazards regression models for outcome of BCR weighted for case-cohort design.
RESULTS: In univariable analysis, every 20-unit increase in the GPS was associated with a nearly threefold increase in risk of BCR (hazard ratio [HR] per 20 units 2.82, P < 0.001). In a multivariable Cox model adjusted for age, race, Cancer of the Prostate Risk Assessment Postsurgical score, Grade Group at the positive margin, and ART, the GPS was significantly associated with BCR (HR 1.56 per 20 units; 95% confidence interval 1.11-2.19; P = 0.011). The study is limited by its retrospective and single institution design.
CONCLUSIONS: The GPS at the positive surgical margin could help stratify prognosis and inform clinical decision-making regarding adjuvant therapy after RP.
摘要：
目的：评估17基因基因组前列腺评分®（GPS；MDxHealth，Irvine,CA,USA）在前列腺癌根治性前列腺切除术（RP）的阳性切缘进行治疗，因为它与随后的生化复发（BCR）的风险有关。
方法：我们为BCR的结局设计了一个病例队列，从2008年至2017年在约翰霍普金斯大学接受治疗的813例RP患者队列中选择223例，具有阳性切缘和可用临床数据；其中，213有可用的组织和临床数据。从与阳性手术切缘相邻的福尔马林固定的石蜡包埋的肿瘤组织中分离出RNA，并且这些患者中的203名可以评估GPS，得分范围为0至100，得分越高表明风险越高。所有患者均接受有或没有辅助放射治疗（ART）的RP。统计分析采用Cox比例风险回归模型对病例队列设计加权的BCR结果进行分析。
结果：在单变量分析中，GPS每增加20个单位,BCR风险增加近3倍(风险比[HR]每20个单位2.82,P<0.001).在根据年龄调整的多变量Cox模型中，种族,前列腺癌术后风险评估评分，正边距的等级组，艺术,GPS与BCR显著相关(HR1.56/20单位;95%置信区间1.11-2.19;P=0.011).这项研究受到其回顾性和单一机构设计的限制。
结论：手术切缘阳性的GPS有助于对预后进行分层，并为RP后辅助治疗的临床决策提供信息。
方法：我们为BCR的结局设计了一个病例队列，从2008年至2017年在约翰霍普金斯大学接受治疗的813例RP患者队列中选择223例，具有阳性切缘和可用临床数据；其中，213有可用的组织和临床数据。从与阳性手术切缘相邻的福尔马林固定的石蜡包埋的肿瘤组织中分离出RNA，并且这些患者中的203名可以评估GPS，得分范围为0至100，得分越高表明风险越高。所有患者均接受有或没有辅助放射治疗（ART）的RP。统计分析采用Cox比例风险回归模型对病例队列设计加权的BCR结果进行分析。
结果：在单变量分析中，GPS每增加20个单位,BCR风险增加近3倍(风险比[HR]每20个单位2.82,P<0.001).在根据年龄调整的多变量Cox模型中，种族,前列腺癌术后风险评估评分，正边距的等级组，艺术,GPS与BCR显著相关(HR1.56/20单位;95%置信区间1.11-2.19;P=0.011).这项研究受到其回顾性和单一机构设计的限制。
结论：手术切缘阳性的GPS有助于对预后进行分层，并为RP后辅助治疗的临床决策提供信息。
