Department of Uro-Oncology, Chris O'Brien Lifehouse, University of Sydney, Sydney, NSW, Australia.
Northern Clinical School, University of Sydney, Sydney, NSW, Australia.
Prostate Cancer Prostatic Dis. 2017 Sep;20(3):352-360. doi: 10.1038/pcan.2017.23. Epub 2017 Apr 25.
Promising therapeutic results of the prostate-specific membrane antigen (PSMA) ligand have been shown when labelling with lutetium-177 (Lu). We performed a systematic review and meta-analysis to assess the therapeutic response of Lu-PSMA in the treatment of metastatic castration-resistant prostate cancer (mCRPC).
A systematic review was conducted using electronic databases up to December 2016. Two reviewers independently extracted data and assessed methodological quality. The main outcome of interest was antitumour biochemical response of Lu-PSMA, analysing two measures: 'any PSA decline' and '>50% decline' from baseline. A random-effects meta-analysis was used to calculate the pooled proportion across studies. The I statistic was calculated in each case to investigate the extent of heterogeneity across the studies. A sensitivity analysis was conducted removing two studies, which were presented as abstracts and proportions were summarised by chemical type (Lu-J591/DKZ/I&T). All analyses were conducted using Stata v14.
A total of 10 studies were included in the analysis giving a total sample size of 369, 220 (of 334 analysable) experienced any PSA decline. The pooled proportion of patients with any PSA decline was 68% (95% confidence interval (CI): 61-74). The I statistic was 39.1% (P=0.11) suggesting minor heterogeneity between results. The pooled proportion of patients with >50% PSA decline was 37% (95% CI: 22-52). The I statistic was 91.0% (P<0.001) suggesting substantial heterogeneity between results. On subgroup analysis, a higher proportion of patients in the Lu-DKZ/I&T subgroup had a PSA decline >50%, however, it can be seen that the Lu-DKZ/I&T subgroup had a substantial amount of heterogeneity across studies.
This review suggests promising early results for the treatment of mCRPC, especially from patients treated with the more recently developed radioligands. Overall, our meta-analysis showed that approximately two-thirds of patients had a biochemical response. Randomised-controlled trials would be necessary to verify its effectiveness against current systemic therapies and create an ideal treatment protocol.
已显示出前列腺特异性膜抗原（PSMA）配体与镥-177（Lu）标记时具有有前景的治疗效果。我们进行了系统评价和荟萃分析，以评估 Lu-PSMA 在治疗转移性去势抵抗性前列腺癌（mCRPC）中的治疗反应。
使用电子数据库进行了系统评价，截至 2016 年 12 月。两位审阅者独立提取数据并评估方法学质量。主要观察结果是 Lu-PSMA 的抗肿瘤生化反应，分析了两个指标：“任何 PSA 下降”和“基线下降>50%”。使用随机效应荟萃分析计算研究间的合并比例。在每种情况下，计算 I 统计量以研究研究间的异质性程度。进行敏感性分析，剔除了两项作为摘要呈现的研究，并按化学类型（Lu-J591/DKZ/I&T）总结比例。所有分析均使用 Stata v14 进行。
共有 10 项研究纳入分析，总样本量为 369 例，其中 220 例（334 例可分析）有任何 PSA 下降。有任何 PSA 下降的患者的合并比例为 68%（95%置信区间（CI）：61-74）。I 统计量为 39.1%（P=0.11），表明结果之间的异质性较小。PSA 下降>50%的患者的合并比例为 37%（95%CI：22-52）。I 统计量为 91.0%（P<0.001），表明结果之间存在大量异质性。在亚组分析中，Lu-DKZ/I&T 亚组中 PSA 下降>50%的患者比例较高，但可以看出 Lu-DKZ/I&T 亚组的研究间存在大量异质性。
这项综述表明，治疗 mCRPC 的早期结果很有前景，特别是对于接受最近开发的放射性配体治疗的患者。总体而言，我们的荟萃分析表明，大约三分之二的患者有生化反应。需要进行随机对照试验来验证其对当前系统治疗的有效性，并制定理想的治疗方案。
