Department of Nuclear Medicine; University of Pretoria and Steve Biko Academic Hospital, Pretoria, South Africa;
Nuclear Medicine Research Infrastructure, Pretoria, South Africa.
J Nucl Med. 2022 Oct;63(10):1496-1502. doi: 10.2967/jnumed.121.263618. Epub 2022 Feb 17.
Ac-PSMA-617, targeting the prostate-specific membrane antigen (PSMA), which is overexpressed on prostate cancer cells, has shown a remarkable therapeutic efficacy in heavily pretreated patients with metastatic castration-resistant prostate carcinoma (mCRPC). Here, we report on treatment outcome and survival using this novel treatment modality in a series of 53 patients with mCRPC directly after their androgen deprivation treatment (ADT). Ac-PSMA-617 was administered to 53 such patients. Ga-PSMA PET/CT was obtained at baseline, before every treatment cycle, and on follow-up to select patients for treatment, determine the activity to be administered, and assess their response. Serial prostate-specific antigen (PSA) measurements were obtained for response assessment. The median age of the patients was 63.4 y (range, 45-83 y). In total, 167 cycles were administered (median, 3; range, 1-7). Forty-eight patients (91%) had a PSA decline of at least 50%, and 51 patients (96%) had any decline in PSA. Ga-PSMA PET findings became negative in 30 patients. In the multivariate analysis, a PSA decline of at least 50% proved predictive of both progression-free survival (PFS) and overall survival (OS), and platelet count also proved predictive for PFS. The median estimated OS was 9 mo for patients with a PSA decline of less than 50% but was not yet reached at the latest follow-up (55 mo) for patients with a PSA decline of 50% or more. The estimated median PFS was 22 mo for patients with a PSA decline of at least 50% and 4 mo for patients with a PSA decline of less than 50%. No severe hematotoxicity was noted, and only 3 patients had grade III-IV nephrotoxicity. The commonest toxicity seen was grade I-II xerostomia, observed in 81% of patients. In 91% of 53 patients with mCRPC, treatment with Ac-PSMA-617 immediately after ADT resulted in at least a 50% decrease in PSA level. Furthermore, a PSA decline of at least 50% proved the single most important factor predicting PFS and OS after Ac-PSMA-617 treatment. Of interest, median OS in patients with a PSA decline of at least 50% was not yet reached at the latest follow-up (55 mo). These favorable results suggest that it would be of major clinical relevance to perform a prospective randomized study comparing Ac-PSMA-617 with current standard-of-care treatment options such as enzalutamide, abiraterone acetate, and docetaxel after ADT.
Ac-PSMA-617 靶向前列腺特异性膜抗原 (PSMA)，该抗原在前列腺癌细胞中过表达，在经过大量预处理的转移性去势抵抗性前列腺癌 (mCRPC) 患者中显示出显著的治疗效果。在这里，我们报告了在一组 53 例直接接受去势治疗 (ADT) 后的 mCRPC 患者中使用这种新治疗方法的治疗结果和生存情况。53 例此类患者接受了 Ac-PSMA-617 治疗。在基线、每个治疗周期前和随访时进行 Ga-PSMA PET/CT 检查，以选择接受治疗的患者、确定要给予的治疗活性并评估其反应。连续测量前列腺特异性抗原 (PSA) 以评估反应。患者的中位年龄为 63.4 岁（范围，45-83 岁）。共给予 167 个周期（中位数为 3 个；范围，1-7 个）。48 例（91%）患者 PSA 下降至少 50%，51 例（96%）患者 PSA 下降。30 例患者 Ga-PSMA PET 检查结果转为阴性。在多变量分析中，PSA 下降至少 50% 可预测无进展生存期 (PFS) 和总生存期 (OS)，血小板计数也可预测 PFS。PSA 下降<50%的患者中位估计 OS 为 9 个月，但在 PSA 下降≥50%的患者中，最新随访（55 个月）尚未达到。PSA 下降≥50%的患者估计中位 PFS 为 22 个月，PSA 下降<50%的患者为 4 个月。未观察到严重的血液毒性，只有 3 例患者出现 III-IV 级肾毒性。最常见的毒性是 I-II 级口干，81%的患者出现。在 53 例 mCRPC 患者中，91%的患者在 ADT 后立即接受 Ac-PSMA-617 治疗，PSA 水平至少下降 50%。此外，PSA 下降至少 50% 是预测 Ac-PSMA-617 治疗后 PFS 和 OS 的最重要因素。有趣的是，PSA 下降≥50%的患者中位 OS 在最新随访（55 个月）时仍未达到。这些有利的结果表明，进行前瞻性随机研究比较 Ac-PSMA-617 与 ADT 后当前的标准治疗选择（如恩扎鲁胺、阿比特龙醋酸酯和多西他赛）将具有重要的临床意义。
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