AI-Based Pathology Classifier Predicts Sensitivity to Enzalutamide in Metastatic Hormone-Sensitive Prostate Cancer: A Biomarker Analysis of the ENZAMET Trial.

We tested whether the artificial intelligence pathology image classifier (APIC), previously developed and locked in CHAARTED, predicts OS benefit from enzalutamide in ENZAMET.

我们测试了之前在CHAARTED中开发并锁定的人工智能病理图像分类器(APIC)是否能预测ENZAMET中恩杂鲁胺的OS获益。

experimental_design

This biomarker study applied APIC to digitized hematoxylin and eosin specimens from ENZAMET [Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) 1304, NCT02446405].

这项生物标志物研究将APIC应用于ENZAMET的数字化苏木精和伊红标本[澳大利亚和新西兰泌尿生殖和前列腺癌试验组(ANZUP) 1304, NCT02446405]。

ENZAMET randomized participants with mHSPC to ADT plus enzalutamide or nonsteroidal antiandrogen (NSAA), with early concurrent docetaxel permitted.

ENZAMET将mHSPC的参与者随机分为ADT加恩杂鲁胺组或非甾体抗雄激素(NSAA)组，允许早期同时使用多西他赛。

APIC was applied without modification or retraining.

APIC的应用没有修改或重新训练。

The prespecified primary analysis evaluated the treatment-by-APIC interaction for OS using Cox models adjusted for standard clinical factors.

预先设定的主要分析评估了使用Cox模型调整标准临床因素后的治疗与APIC交互作用对OS的影响。

Prespecified sensitivity analysis excluded participants receiving early concurrent docetaxel.

预先设定的敏感性分析排除了接受早期同时多西他赛的参与者。

Results

Among 1,125 participants, 492 with digitized tissue (median follow-up, 68.8 months) were eligible.

在1,125名参与者中，有492名具有数字化组织（中位随访时间，68.8个月）符合资格。

APIC classified 316 (64%) as APIC negative and 176 (36%) as APIC positive.

APIC将316例(64%)分类为APIC阴性，176例(36%)为APIC阳性。

APIC significantly modified enzalutamide benefit (interaction P = 0.014).

APIC显著改变了恩杂鲁胺的益处（交互作用P = 0.014）。

APIC-negative disease showed improved survival with enzalutamide versus NSAA [HR, 0.50; 95% confidence interval(CI), 0.35-0.73; 60-month OS, 76.5% vs. 58.3%], whereas APIC-positive disease showed limited evidence of benefit (HR, 1.04; 95% CI, 0.67-1.62; 60-month OS, 55.6% vs. 58.8%).

APIC阴性疾病的患者在接受恩杂鲁胺治疗后，生存率有所提高，与NSAA相比[风险比，0.50；95%置信区间(CI)，0.35-0.73；60个月总生存率，76.5%对58.3%]，而APIC阳性疾病的患者显示出有限的益处证据（风险比，1.04；95% CI，0.67-1.62；60个月总生存率，55.6%对58.8%）。

In low-volume disease, enzalutamide improved survival in APIC-negative (HR, 0.31; 95% CI, 0.16-0.62) but not APIC-positive disease (HR, 1.04; 95% CI, 0.53-2.06; interaction P = 0.015).

在低体积疾病中，恩杂鲁胺改善了APIC阴性患者的生存率（风险比，0.31；95% CI，0.16-0.62），但对APIC阳性疾病患者没有改善（风险比，1.04；95% CI，0.53-2.06；交互作用P = 0.015）。

For non-docetaxel-treated participants, enzalutamide benefit was greater in APIC-negative (HR, 0.40; 60-month OS 82% vs. 61.0%) than in APIC-positive participants (HR, 0.79; 60-month OS, 62.8% vs. 57.6%).

对于未接受多西他赛治疗的参与者，恩杂鲁胺在APIC阴性患者中的益处更大（风险比，0.40；60个月总生存率82%对61.0%）相比于APIC阳性患者（风险比，0.79；60个月总生存率，62.8%对57.6%）。

Conclusions

The presence of APIC-negative disease identified participants with a major improvement in OS with the addition of enzalutamide to ADT compared with the addition of NSAA.

APIC阴性疾病的出现，确定了与ADT联合使用恩杂鲁胺相比，联合使用NSAA的患者总生存率有显著改善。