Department of Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, 0001, South Africa.
Nuclear Medicine Research Infrastructure (NuMeRI), Pretoria, South Africa.
Eur J Nucl Med Mol Imaging. 2023 Jun;50(7):2210-2218. doi: 10.1007/s00259-023-06165-9. Epub 2023 Mar 3.
Ac-PSMA-617 has demonstrated good anti-tumor effect as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients. No study has previously assessed treatment outcome and survival following Ac-PSMA-617 treatment of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC) patients. Based on the potential side effects that are known and explained to the patients by the oncologist, some of the patients refused the standard treatment and are seeking alternative therapies. Thus, we report our preliminary findings in a retrospective series of 21 mHSPC patients that refused standard treatment options and were treated with Ac-PSMA-617.
We retrospectively reviewed patients with histologically confirmed de novo treatment-naïve bone ± visceral mHSPC that were treated with Ac-PSMA-617 radioligand therapy (RLT). Inclusion criteria included an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, treatment-naive bone ± visceral mHSPC, and patients refusal for ADT ± docetaxel, abiraterone acetate, or enzalutamide. We evaluated the response to treatment using prostate-specific antigen (PSA) response and the progression-free survival (PFS) and overall survival (OS) as well as the toxicities.
Twenty-one mHSPC patients were included in this preliminary work. Following treatment, twenty patients (95%) had any decline in PSA and eighteen patients (86%) presented with a PSA decline of ≥ 50% including 4 patients in whom PSA became undetectable. A lower percentage decrease in PSA following treatment was associated with increased mortality and shorter progression-free survival. Overall, administration of Ac-PSMA-617 was well tolerated. The commonest toxicity seen was grade I/II dry mouth observed in 94% of patients.
Given these favorable results, randomized prospective multicenter trials assessing the clinical value of Ac-PSMA-617 as a therapeutic agent for mHSPC administered either as monotherapy or administered concomitant with ADT are of interest.
Ac-PSMA-617 作为转移性去势抵抗性前列腺癌（mCRPC）患者的治疗选择，已显示出良好的抗肿瘤效果。以前没有研究评估过 Ac-PSMA-617 治疗初发转移性激素敏感性前列腺癌（mHSPC）患者的治疗结果和生存情况。基于已知的潜在副作用，并由肿瘤学家向患者解释，一些患者拒绝了标准治疗，正在寻求替代疗法。因此，我们报告了 21 例初治 mHSPC 患者的回顾性系列研究结果，这些患者拒绝了标准治疗方案，并接受了 Ac-PSMA-617 治疗。
我们回顾性分析了经组织学证实的初治、无骨转移±内脏转移 mHSPC 患者，他们接受了 Ac-PSMA-617 放射性配体治疗（RLT）。纳入标准包括 Eastern Cooperative Oncology Group（ECOG）体能状态为 0 至 2 分、初治骨±内脏 mHSPC 患者，以及拒绝 ADT±多西他赛、阿比特龙、或恩杂鲁胺治疗的患者。我们使用前列腺特异性抗原（PSA）应答和无进展生存期（PFS）和总生存期（OS）评估治疗反应，并评估了毒性。
本初步研究纳入了 21 例 mHSPC 患者。治疗后，20 例（95%）患者的 PSA 有任何下降，18 例（86%）患者的 PSA 下降≥50%，包括 4 例 PSA 降至不可检测水平。治疗后 PSA 下降百分比较低与死亡率增加和无进展生存期缩短相关。总的来说，Ac-PSMA-617 给药的耐受性良好。最常见的毒性是 94%的患者出现 1/2 级口干。
鉴于这些有利的结果，评估 Ac-PSMA-617 作为 mHSPC 治疗药物的临床价值的随机前瞻性多中心试验很有意义，这些试验可以评估 Ac-PSMA-617 作为单药或与 ADT 联合应用的疗效。
