Metastatic prostate carcinoma overexpresses prostate-specific membrane antigen (PSMA), making this antigen a suitable target for radioligand therapy of the disease. Here we report on our experience with a series of 73 castration-resistant prostate carcinoma patients treated with 225Ac-PSMA-617, identifying variables predictive for overall survival (OS) and progression-free survival (PFS) after 225Ac-PSMA-617 treatment. Methods: 225Ac-PSMA-617 was administered to patients who had metastatic castration-resistant prostate carcinoma and who had exhausted available therapy options for their disease. Full blood count, glomerular filtration rate, and liver function test were obtained at baseline and on follow-up for evaluation of toxicity. 68Ga-PSMA PET/CT was obtained at baseline, before every treatment cycle, and on follow-up for selection of patients for treatment, to determine the activity of the treatment agent to be administered, and for response assessment. Serial prostate-specific antigen (PSA) was obtained for PSA response assessment. Results: Seventy-three men (mean age, 69 y; range, 45-85 y) with metastatic castration-resistant prostate carcinoma were treated with 210 cycles of 225Ac-PSMA-617. In 70% of patients, a PSA decline of greater than or equal to 50% was obtained; 82% of patients had any PSA decline. In 29% of patients, all lesions on 68Ga-PSMA PET resolved in response to treatment. During follow-up, 23 patients experienced disease progression, whereas 13 patients died from their disease. The estimated median PFS and OS were 15.2 mo (95% CI, 13.1-17.4) and 18 mo (95% CI, 16.2-19.9), respectively. In univariate analyses, factors such as baseline PSA, any PSA decline, PSA decline of greater than or equal to 50%, prior chemotherapy, prior radiation therapy, and baseline hemoglobin level were associated with longer PFS and OS (all Ps < 0.05). In multivariate analyses, there was a negative association between prior 177Lu-PSMA therapy and PFS, and a positive association between PSA decline of greater or equal to 50% and PFS. Only a PSA decline of greater than or equal to 50% remained significantly associated with OS on multivariate analyses. Xerostomia was seen in 85% of patients but was not severe enough to warrant discontinuing treatment. Anemia was seen in 27 patients; no patients had grade IV bone marrow toxicity. Renal failure of grade III or IV was seen in 5 patients with baseline renal impairment. Conclusion: In this study, a PSA decline of greater than or equal to 50% after treatment with 225Ac-PSMA-617 was proven by multivariate analyses to be significantly associated with OS and PFS. Furthermore, previous 177Lu-PSMA treatment was negatively associated with PFS in both univariate and multivariate analyses.

中文翻译：

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接受225Ac-PSMA-617放射配体治疗的转移去势抵抗前列腺癌患者的总体生存率和无病生存率的预测指标。

转移性前列腺癌过表达前列腺特异性膜抗原（PSMA），使该抗原成为该疾病放射性配体治疗的合适靶标。在这里，我们报告了我们对73例接受225Ac-PSMA-617治疗的去势抵抗性前列腺癌患者的经验，确定了预测225Ac-PSMA-617治疗后的总生存期（OS）和无进展生存期（PFS）的变量。方法：对患有转移性去势抵抗性前列腺癌且力竭其疾病的可用治疗方法的患者给予225Ac-PSMA-617。在基线和随访时获得全血细胞计数，肾小球滤过率和肝功能测试以评估毒性。在每个治疗周期之前，在基线时获得68Ga-PSMA PET / CT，并在随访中选择要治疗的患者，确定所用治疗剂的活性，并进行疗效评估。获得串行前列腺特异性抗原（PSA）用于PSA反应评估。结果：73例男性（平均年龄69岁；范围45-85岁）患有转移性去势抵抗性前列腺癌，接受了210个周期的225Ac-PSMA-617治疗。在70％的患者中，PSA下降幅度大于或等于50％；82％的患者PSA下降。在29％的患者中，68Ga-PSMA PET上的所有病变均对治疗有所缓解。在随访期间，有23名患者经历了疾病进展，而13名患者则死于疾病。估计的中位PFS和OS分别为15.2 mo（95％CI，13.1-17.4）和18 mo（95％CI，16.2-19.9）。在单变量分析中，诸如基线PSA，任何PSA下降，PSA下降大于或等于50％，先前的化学疗法，先前的放射治疗和基线血红蛋白水平等因素与更长的PFS和OS相关（所有Ps <0.05）。在多变量分析中，先前的177Lu-PSMA治疗与PFS之间存在负相关，而PSA下降大于或等于50％与PFS之间存在正相关。在多变量分析中，只有PSA下降幅度大于或等于50％才与OS显着相关。在85％的患者中可见口干症，但严重程度不足以终止治疗。27例患者出现贫血。没有患者有IV级骨髓毒性。在5名基线肾功能不全的患者中观察到III或IV级肾功能衰竭。结论：在这项研究中，多变量分析证明，用225Ac-PSMA-617治疗后PSA下降大于或等于50％与OS和PFS显着相关。此外，在单变量和多变量分析中，先前的177Lu-PSMA治疗与PFS均呈负相关。