Background Radiotherapy is an effective treatment of intermediate/high-risk locally advanced prostate cancer, however, >30% of patients relapse within 5 years. Clinicopathological parameters currently fail to identify patients prone to systemic relapse and those whom treatment intensification may be beneficial. The purpose of this study was to independently validate the performance of a 70-gene Metastatic Assay in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Patients and methods A bridging cohort of prostate cancer diagnostic biopsy specimens was profiled to enable optimization of the Metastatic Assay threshold before further independent clinical validation in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Multivariable Cox proportional hazard regression analysis was used to assess assay performance in predicting biochemical failure-free survival (BFFS) and metastasis-free survival (MFS). Results Gene expression analysis was carried out in 248 patients from the independent validation cohort and the Metastatic Assay applied. Ten-year MFS was 72% for Metastatic Assay positive patients and 94% for Metastatic Assay negative patients [HR = 3.21 (1.35-7.67); P = 0.003]. On multivariable analysis the Metastatic Assay remained predictive for development of distant metastases [HR = 2.71 (1.11-6.63); P = 0.030]. The assay retained independent prognostic performance for MFS when assessed with the Cancer of the Prostate Assessment Score (CAPRA) [HR = 3.23 (1.22-8.59); P = 0.019] whilst CAPRA itself was not significant [HR = 1.88, (0.52-6.77); P = 0.332]. A high concordance [100% (61.5-100)] for the assay result was noted between two separate foci taken from 11 tumours, whilst Gleason score had low concordance. Conclusions The Metastatic Assay demonstrated significant prognostic performance in patients treated with radical radiotherapy both alone and independent of standard clinical and pathological variables. The Metastatic Assay could have clinical utility when deciding upon treatment intensification in high-risk patients. Genomic and clinical data are available as a public resource.

中文翻译：

---

使用活组织检查以改善接受根治性放射疗法治疗的前列腺癌患者的危险分层的转移试验的验证。

背景技术放射疗法是中/高危局部晚期前列腺癌的有效治疗方法，但是，> 30％的患者在5年内复发。目前，临床病理参数未能识别出容易出现全身性复发的患者，那些需要加强治疗的患者可能会受益。这项研究的目的是独立地从一项接受根治性放射治疗和雄激素剥夺治疗的患者的诊断性活检队列中验证一项70基因转移检测的性能。患者和方法对一组桥接的前列腺癌诊断性活检标本进行分析，以优化转移测定的阈值，然后再对来自接受根治性放疗和雄激素剥夺治疗的患者的诊断性活检进行进一步的独立临床验证。使用多变量Cox比例风险回归分析来评估测定方法在预测无生化失败生存期（BFFS）和无转移生存期（MFS）方面的性能。结果在独立验证队列中对248例患者进行了基因表达分析，并应用了转移测定法。转移测定阳性患者的十年MFS为72％，转移测定阴性患者为94％[HR = 3.21（1.35-7.67）；P = 0.003]。在多变量分析中，转移分析仍可预测远处转移的发生率[HR = 2.71（1.11-6.63）；P = 0.030]。当用前列腺癌评估分数（CAPRA）进行评估时，该测定法保留了MFS的独立预后性能[HR = 3.23（1.22-8.59）；P = 0.019]，而CAPRA本身并不显着[HR = 1.88，（0.52-6.77）; P ＝ 0.332]。从11个肿瘤中分离出的两个病灶之间，检测结果的一致性较高[100％（61.5-100）]，而格里森评分的一致性较低。结论转移试验证明了单独接受根治性放射治疗且独立于标准临床和病理变量的患者的预后良好。在确定高危患者的治疗强度时，转移分析可能具有临床意义。基因组和临床数据可作为公共资源获得。结论转移试验证明了单独接受根治性放射治疗且独立于标准临床和病理变量的患者的预后良好。在确定高危患者的治疗强度时，转移分析可能具有临床意义。基因组和临床数据可作为公共资源获得。结论转移试验证明了单独接受根治性放射治疗且独立于标准临床和病理变量的患者的预后良好。在确定高危患者的治疗强度时，转移分析可能具有临床意义。基因组和临床数据可作为公共资源获得。