Department of Radiation Oncology, University of Michigan, Ann Arbor, MI.
Department of Biostatistics, University of Michigan, Ann Arbor, MI.
J Clin Oncol. 2020 Sep 10;38(26):3024-3031. doi: 10.1200/JCO.19.03217. Epub 2020 May 12.
In men with localized prostate cancer, the addition of androgen-deprivation therapy (ADT) or a brachytherapy boost (BT) to external beam radiotherapy (EBRT) have been shown to improve various oncologic end points. Practice patterns indicate that those who receive BT are significantly less likely to receive ADT, and thus we sought to perform a network meta-analysis to compare the predicted outcomes of a randomized trial of EBRT plus ADT versus EBRT plus BT.
A systematic review identified published randomized trials comparing EBRT with or without ADT, or EBRT (with or without ADT) with or without BT, that reported on overall survival (OS). Standard fixed-effects meta-analyses were performed for each comparison, and a meta-regression was conducted to adjust for use and duration of ADT. Network meta-analyses were performed to compare EBRT plus ADT versus EBRT plus BT. Bayesian analyses were also performed, and a rank was assigned to each treatment after Markov Chain Monte Carlo analyses to create a surface under the cumulative ranking curve.
Six trials compared EBRT with or without ADT (n = 4,663), and 3 compared EBRT with or without BT (n = 718). The addition of ADT to EBRT improved OS (hazard ratio [HR], 0.71 [95% CI, 0.62 to 0.81]), whereas the addition of BT did not significantly improve OS (HR, 1.03 [95% CI, 0.78 to 1.36]). In a network meta-analysis, EBRT plus ADT had improved OS compared with EBRT plus BT (HR, 0.68 [95% CI, 0.52 to 0.89]). Bayesian modeling demonstrated an 88% probability that EBRT plus ADT resulted in superior OS compared with EBRT plus BT.
Our findings suggest that current practice patterns of omitting ADT with EBRT plus BT may result in inferior OS compared with EBRT plus ADT in men with intermediate- and high-risk prostate cancer. ADT for these men should remain a critical component of treatment regardless of radiotherapy delivery method until randomized evidence demonstrates otherwise.
在局限性前列腺癌患者中，雄激素剥夺疗法（ADT）或近距离放射治疗（BT）的加入已被证明可以改善各种肿瘤学终点。实践模式表明，接受 BT 的患者接受 ADT 的可能性明显降低，因此我们试图进行一项网络荟萃分析，以比较 EBRT 加 ADT 与 EBRT 加 BT 的随机试验的预测结果。
系统评价确定了已发表的比较 EBRT 加或不加 ADT 或 EBRT（加或不加 ADT）加或不加 BT 的随机试验，报告了总生存率（OS）。对每项比较进行了标准固定效应荟萃分析，并进行了荟萃回归以调整 ADT 的使用和持续时间。进行了网络荟萃分析，以比较 EBRT 加 ADT 与 EBRT 加 BT。还进行了贝叶斯分析，并在 Markov Chain Monte Carlo 分析后对每种治疗方法进行排名，以创建累积排名曲线下的表面。
六项试验比较了 EBRT 加或不加 ADT（n = 4663），三项试验比较了 EBRT 加或不加 BT（n = 718）。EBRT 加 ADT 可改善 OS（风险比[HR]，0.71[95%CI，0.62 至 0.81]），而 BT 的加入并未显著改善 OS（HR，1.03[95%CI，0.78 至 1.36]）。在网络荟萃分析中，EBRT 加 ADT 与 EBRT 加 BT 相比，OS 得到改善（HR，0.68[95%CI，0.52 至 0.89]）。贝叶斯建模表明，EBRT 加 ADT 与 EBRT 加 BT 相比，OS 更好的概率为 88%。
我们的研究结果表明，目前在中高危前列腺癌患者中，EBRT 加 BT 省略 ADT 的实践模式可能导致 OS 低于 EBRT 加 ADT。对于这些患者，ADT 仍然应该是治疗的关键组成部分，无论放疗的方法如何，直到随机证据表明否则。
