一项关于在接受晚期前列腺癌治疗的男性中前列腺特异性膜抗原（PSMA）动态变化的初步研究。
A pilot study of prostate-specific membrane antigen (PSMA) dynamics in men undergoing treatment for advanced prostate cancer.
机构信息
Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland.
Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
出版信息
Prostate. 2019 Oct;79(14):1597-1603. doi: 10.1002/pros.23883. Epub 2019 Jul 30.
BACKGROUND
Prostate-specific membrane antigen (PSMA) is a rational target for noninvasive detection of recurrent prostate cancer (PCa) and for therapy of metastatic castration-resistant prostate cancer (mCRPC) with PSMA-targeted agents. Here we conducted serial measurements of PSMA expression on circulating tumor cells (CTCs) to evaluate patterns of longitudinal PSMA dynamics over the course of multiple sequential therapies.
METHODS
A retrospective investigation of men with mCRPC undergoing evaluation at medical oncology clinics at our institution assessed the dynamics of PSMA expression in the context of different systemic treatments administered sequentially. Eligibility included patients who began systemic therapies with androgen receptor (AR)-directed agents or taxane agents for whom peripheral blood samples were tested for CTC mRNA of AR splice variant-7 (AR-V7), prostate-specific antigen (PSA), and PSMA (with >2 CTC + results) in a CLIA-accredited laboratory.
RESULTS
From August 2015 to November 2017, we identified 96 eligible men. Fifteen had greater than or equal to 2 sequential therapies and evaluable CTC samples, greater than or equal to 1 expressing PSMA (PSMA+). Among the 15 patients included in this analysis, a total of 54 PSMA status evaluations were performed in the context of 48 therapies during a median follow-up of 18 months. At baseline, PSMA signal was detected ("positive") in 11 of 15 (73.3%) patients, while for 4 of 15 (26.7%) patients PSMA signal was undetectable ("negative"). In all but two patients, the baseline collection corresponded with a change in treatment. On the second assessment, PSMA increases were detected in all 4/4 (100%) PSMA-negative patients and 8 of 11 (72.7%) PSMA-positive patients. PSMA significantly decreased in a patient treated with Lu-PSMA-617. Serum PSA declines were seen in 7 of 8 (88%) of the treatment periods where PSMA decreased.
CONCLUSIONS
PSMA expression in CTCs is a dynamic marker. PSMA transcript declines appear to be associated with concurrent decreases in serum PSA. Sequential CTC sampling could provide a noninvasive response assessment to systemic treatment for mCRPC.
背景
前列腺特异性膜抗原（PSMA）是一种合理的靶点，可用于非侵入性检测复发性前列腺癌（PCa），并可使用 PSMA 靶向药物治疗转移性去势抵抗性前列腺癌（mCRPC）。在这里，我们对在我院肿瘤内科接受治疗的 mCRPC 男性患者进行了循环肿瘤细胞（CTC）中 PSMA 表达的连续测量，以评估多次连续治疗过程中 PSMA 动态的纵向模式。
方法
对在我院肿瘤内科接受治疗的 mCRPC 男性患者进行了回顾性研究，评估了不同系统治疗中 PSMA 表达的动态变化。入选标准包括开始接受雄激素受体（AR）靶向药物或紫杉烷药物治疗且外周血 CTC 信使 RNA 检测到 AR 剪接变体-7（AR-V7）、前列腺特异性抗原（PSA）和 PSMA（≥2 个 CTC+结果）的患者，这些检测均在 CLIA 认证实验室进行。
结果
2015 年 8 月至 2017 年 11 月，我们共确定了 96 名符合条件的男性患者。其中 15 名患者接受了≥2 次连续治疗，且可评估 CTC 样本≥1 个表达 PSMA（PSMA+）。在这项分析中，纳入了 15 名患者，共进行了 54 次 PSMA 状态评估，其中 48 次治疗在中位随访 18 个月时进行。在基线时，15 名患者中有 11 名（73.3%）患者的 PSMA 信号检测到（“阳性”），而 15 名患者中有 4 名（26.7%）患者的 PSMA 信号未检测到（“阴性”）。在除两名患者以外的所有患者中，基线采集与治疗变化相对应。在第二次评估时，4 名（100%）PSMA 阴性患者和 11 名（72.7%）PSMA 阳性患者的 PSMA 均有升高。在接受 Lu-PSMA-617 治疗的患者中，PSMA 显著降低。在 PSMA 降低的 8 个治疗期中有 7 个（88%）患者的血清 PSA 下降。
结论
CTC 中 PSMA 的表达是一个动态标志物。PSMA 转录物的下降似乎与同时发生的血清 PSA 下降有关。连续 CTC 采样可为 mCRPC 的系统治疗提供一种非侵入性的反应评估。
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