Background

A 17-gene biopsy-based reverse transcription polymerase chain reaction assay, which provides a Genomic Prostate Score (GPS—scale 0–100), has been validated as an independent predictor of adverse pathology and biochemical recurrence after radical prostatectomy (RP) in men with low- and intermediate-risk prostate cancer (PCa).

Objective

To evaluate GPS as a predictor of PCa metastasis and PCa-specific death (PCD) in a large cohort of men with localized PCa and long-term follow-up.

Design, setting, and participants

A retrospective study using a stratified cohort sampling design was performed in a cohort of men treated with RP within Kaiser Permanente Northern California. RNA from archival diagnostic biopsies was assayed to generate GPS results.

Outcome measurements and statistical analysis

We assessed the association between GPS and time to metastasis and PCD in prespecified uni- and multivariable statistical analyses, based on Cox proportional hazard models accounting for sampling weights.

Results and limitations

The final study population consisted of 279 men with low-, intermediate-, and high-risk PCa between 1995 and 2010 (median follow-up 9.8 yr), and included 64 PCD and 79 metastases. Valid GPS results were obtained for 259 (93%). In univariable analysis, GPS was strongly associated with time to PCD, hazard ratio (HR)/20 GPS units = 3.23 (95% confidence interval [CI] 1.84–5.65; p < 0.001), and time to metastasis, HR/20 units = 2.75 (95% CI 1.63–4.63; p < 0.001). The association between GPS and both end points remained significant after adjusting for National Comprehensive Cancer Network, American Urological Association, and Cancer of the Prostate Risk Assessment (CAPRA) risks (p < 0.001). No patient with low- or intermediate-risk disease and a GPS of < 20 developed metastases or PCD (n = 31). In receiver operating characteristic analysis of PCD at 10 yr, GPS improved the c-statistic from 0.78 (CAPRA alone) to 0.84 (GPS + CAPRA; p < 0.001). A limitation of the study was that patients were treated during an era when definitive treatment was standard of care with little adoption of active surveillance.

Conclusions

GPS is a strong independent predictor of long-term outcomes in clinically localized PCa in men treated with RP and may improve risk stratification for men with newly diagnosed disease.

Patient summary

Many prostate cancers are slow growing and unlikely to spread or threaten a man's life, while others are more aggressive and require treatment. Increasingly, doctors are using new molecular tests, such as the17-gene Genomic Prostate Score (GPS), which can be performed at the time of initial diagnosis to help determine how aggressive a given patient's cancer may be. In this study, performed in a large community-based healthcare network, GPS was shown to be a strong predictor as to whether a man's prostate cancer will spread and threaten his life after surgery, providing information that may help patients and their doctors decide on the best course of management of their disease.

中文翻译：

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基于活检的17基因基因前列腺评分，作为具有临床局限性疾病的接受手术治疗的男性的转移和前列腺癌死亡的预测因子

背景

基于17基因活检的逆转录聚合酶链反应分析可提供男性前列腺癌基因组评分（GPS，等级0-100），已被证实可作为男性前列腺癌根治术（RP）后不良病理学和生化复发的独立预测因子中低危前列腺癌（PCa）。

客观的

要评估GPS作为预测大量PCa本地化和长期随访的男性人群中PCa转移和PCa特异性死亡（PCD）的预测指标。

设计，设置和参与者

一项回顾性研究采用分层队列抽样设计，在北加州凯撒永久居民的一组接受RP治疗的男性中进行。分析来自档案存档的活检组织的RNA，以生成GPS结果。

成果测量和统计分析

在预先确定的单变量和多变量统计分析中，我们基于考虑了采样权重的Cox比例风险模型，评估了GPS与转移时间和PCD之间的关联。

结果与局限性

最终研究人群包括1995年至2010年（中位随访9.8年）的279名患有低，中和高风险PCa的男性，其中包括64名PCD和79例转移。获得了259个（93％）的有效GPS结果。在单变量分析中，GPS与PCD时间，危险比（HR）/ 20 GPS单位= 3.23（95％置信区间[CI] 1.84-5.65；p  <0.001）和转移时间，HR / 20单位密切相关。= 2.75（95％CI 1.63–4.63；p  <0.001）。在调整了国家综合癌症网络，美国泌尿科协会和前列腺癌风险评估（CAPRA）风险后，GPS与两个终点之间的关联仍然很显着（p <0.001）。没有低危或中危疾病且GPS ＜20的患者发生转移或PCD（n  = 31）。在10年PCD的接收器工作特性分析中，GPS将c统计量从0.78（仅CAPRA）提高到0.84（GPS + CAPRA；p  <0.001）。该研究的局限性在于，在明确的治疗是标准治疗且很少采用主动监测的时代里，对患者进行了治疗。

结论

GPS是接受RP治疗的男性临床局部PCa长期结果的有力独立预测指标，可能会改善新诊断疾病男性的风险分层。

病人总结

许多前列腺癌生长缓慢，不太可能扩散或威胁男人的生命，而另一些则更具侵略性，需要治疗。医生越来越多地使用新的分子检测，例如17基因的基因组前列腺评分（GPS），可以在初次诊断时进行该检测，以帮助确定特定患者的癌症可能有多大攻击性。在一项大型的社区医疗网络中进行的这项研究中，GPS被证明是一个人的前列腺癌是否会在手术后扩散并威胁其生命的强有力的预测指标，它提供的信息可以帮助患者及其医生决定疾病的最佳治疗过程。