Background

Prostate cancer patients who have a detectable prostate-specific antigen (PSA) postprostatectomy may harbor pre-existing metastatic disease. To our knowledge, none of the commercially available genomic biomarkers have been investigated in such men.

Objective

To evaluate if a 22-gene genomic classifier can independently predict development of metastasis in men with PSA persistence postoperatively.

Design, setting, and participants

A multi-institutional study of 477 men who underwent radical prostatectomy (RP) between 1990 and 2015 from three academic centers. Patients were categorized as detectable PSA (n = 150) or undetectable (n = 327) based on post-RP PSA nadir ≥0.1 ng/ml.

Outcome measurements and statisitical analysis

Cumulative incidence curves for metastasis were constructed using Fine-Gray competing risks analysis. Penalized Cox univariable and multivariable (MVA) proportional hazards models were performed to evaluate the association of the genomic classifier with metastasis.

Results and limitations

The median follow-up for censored patients was 57 mo. The median time from RP to first postoperative PSA was 1.4 mo. Detectable PSA patients were more likely to have higher adverse pathologic features compared with undetectable PSA patients. On MVA, only genomic high-risk (hazard ratio [HR]: 5.95, 95% confidence interval [CI]: 2.02–19.41, p = 0.001), detectable PSA (HR: 4.26, 95% CI: 1.16–21.8, p = 0.03), and lymph node invasion (HR: 12.2, 95% CI: 2.46–70.7, p = 0.003) remained prognostic factors for metastasis. Among detectable PSA patients, the 5-yr metastasis rate was 0.90% for genomic low/intermediate and 18% for genomic high risk (p < 0.001). Genomic high risk remained independently prognostic on MVA (HR: 5.61, 95% CI: 1.48–22.7, p = 0.01) among detectable PSA patients. C-index for Cancer of the Prostate Risk Assessment Postsurgical score, Gandaglia nomogram, and the genomic classifier plus either Cancer of the Prostate Risk Assessment Postsurgical score or Gandaglia were 0.69, 0.68, and 0.82 or 0.81, respectively. Sample size was a limitation.

Conclusions

Despite patients with a detectable PSA harboring significantly higher rates of aggressive clinicopathologic features, Decipher independently predicts for metastasis. Prospective validation of these findings is warranted and will be collected as part of the ongoing randomized trial NRG GU-002.

Patient summary

Decipher independently predicted metastasis for patients with detectable prostate-specific antigen after prostatectomy.

中文翻译：

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前列腺癌基因分类器在前列腺特异性抗原持久性前列腺切除术后男性转移预测中的作用

背景

前列腺癌患者在前列腺切除术后可检出前列腺特异性抗原（PSA），可能患有前列腺癌。据我们所知，尚未在此类男性中研究任何可商购的基因组生物标记。

客观的

为了评估22基因基因组分类器是否可以独立预测术后PSA持续性男性的转移发展。

设计，设置和参与者

该研究由三个学术中心对1990年至2015年间接受根治性前列腺切除术（RP）的477名男性进行的多机构研究。 根据RP后PSA最低点≥0.1ng / ml ，将患者分为可检出PSA（n  = 150）或未检出（n = 327）。

成果测量和统计分析

使用Fine-Gray竞争风险分析构建转移的累积发生率曲线。进行了惩罚性Cox单变量和多变量（MVA）比例风险模型，以评估基因组分类器与转移的关系。

结果与局限性

接受检查的患者的中位随访时间为57 mo。从RP到首次术后PSA的中位时间为1.4个月。与未检测到的PSA患者相比，可检测到的PSA患者更有可能具有更高的不良病理特征。在MVA上，只有基因组高风险（危险比[HR]：5.95，95％置信区间[CI]：2.02–19.41，p  = 0.001），可检测到PSA（HR：4.26，95％CI：1.16–21.8，p  = 0.03），淋巴结浸润（HR：12.2，95％CI：2.46-70.7，p  = 0.003）仍然是转移的预后因素。在可检测到的PSA患者中，基因组低/中度患者的5年转移率为0.90％，而基因组高危患者的5年转移率为18％（p <0.001）。 在可检测到的PSA患者中，基因组高风险仍独立于MVA的预后（HR：5.61，95％CI：1.48-22.7，p = 0.01）。前列腺癌风险评估术后分数的C指数，Gandaglia nomogram和基因组分类器以及前列腺癌风险评估术后分数或Gandaglia的C指数分别为0.69、0.68和0.82或0.81。样本量有限。

结论

尽管有可检测到的PSA的患者具有较高的侵袭性临床病理特征，但Decipher独立预测转移。有必要对这些发现进行前瞻性验证，并将其作为正在进行的随机试验NRG GU-002的一部分进行收集。

病人总结

解密者独立预测前列腺切除术后可检测到的前列腺特异性抗原患者的转移。