Department of Nuclear Medicine, School of Medicine, Technical University of Munich, Munich, Germany;
Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
J Nucl Med. 2023 Aug;64(8):1252-1258. doi: 10.2967/jnumed.122.265346. Epub 2023 Jun 8.
Prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) has shown encouraging results for treatment of metastatic castration-resistant prostate cancer (mCRPC) in the prospective, multicenter, randomized phase II TheraP study. The inclusion criteria for that study comprised a pretherapeutic Ga-PSMA-11 PET scan showing sufficient tumor uptake using a predefined threshold and the absence of F-FDG-positive, PSMA ligand-negative tumor lesions. However, the prognostic value of these PET-based inclusion criteria remains unclear. Therefore, we evaluated the outcome of mCRPC patients treated with PSMA RLT using TheraP as well as other TheraP-based PET inclusion criteria. First, patients were dichotomized into 2 groups whose PSMA PET scans did (TheraP contrast-enhanced PSMA [cePSMA] PET-positive) or did not (TheraP cePSMA PET-negative) fulfill the inclusion criteria of TheraP. Notably, unlike in TheraP, F-FDG PET was not performed on our patients. Prostate-specific antigen (PSA) response (PSA decline ≥ 50% from baseline), PSA progression-free survival, and overall survival (OS) were compared. Additionally, patients were further dichotomized according to predefined SUV thresholds different from those used in TheraP to analyze their potential impact on outcome as well. In total, 107 mCRPC patients were included in this analysis (TheraP cePSMA PET-positive, = 77; TheraP cePSMA PET-negative, = 30). PSA response rates were higher in TheraP cePSMA PET-positive patients than in TheraP cePSMA PET-negative patients (54.5% vs. 20%, respectively; = 0.0012). The median PSA progression-free survival ( = 0.007) and OS ( = 0.0007) of patients were significantly longer in the TheraP cePSMA PET-positive group than in the TheraP cePSMA PET-negative group. Moreover, being in the TheraP cePSMA PET-positive group was identified as a significant prognosticator of longer OS ( = 0.003). The application of different SUV thresholds for a single hottest lesion demonstrated no influence on outcome in patients eligible for PSMA RLT. Patient selection for PSMA RLT according to the inclusion criteria of TheraP led to a better treatment response and outcome in our preselected patient cohort. However, a relevant number of patients not fulfilling these criteria also showed substantial rates of response.
前列腺特异性膜抗原（PSMA）放射性配体治疗（RLT）在前瞻性、多中心、随机 II 期 TheraP 研究中显示出治疗转移性去势抵抗性前列腺癌（mCRPC）的可喜结果。该研究的纳入标准包括治疗前 Ga-PSMA-11 PET 扫描显示使用预设阈值的足够肿瘤摄取，以及不存在 F-FDG 阳性、PSMA 配体阴性的肿瘤病变。然而，这些基于 PET 的纳入标准的预后价值仍不清楚。因此，我们评估了使用 TheraP 以及其他基于 TheraP 的 PET 纳入标准治疗的 mCRPC 患者的结果。首先，将患者分为两组，一组 PSMA PET 扫描符合（TheraP 对比增强 PSMA [cePSMA] PET 阳性），另一组不符合（TheraP cePSMA PET 阴性）TheraP 的纳入标准。值得注意的是，与 TheraP 不同，我们的患者未进行 F-FDG PET 检查。比较前列腺特异性抗原（PSA）反应（PSA 从基线下降≥50%）、PSA 无进展生存期和总生存期（OS）。此外，根据与 TheraP 不同的预设 SUV 阈值进一步将患者分为两组，以分析其对结果的潜在影响。共有 107 例 mCRPC 患者纳入本分析（TheraP cePSMA PET 阳性，n=77；TheraP cePSMA PET 阴性，n=30）。TheraP cePSMA PET 阳性患者的 PSA 反应率高于 TheraP cePSMA PET 阴性患者（分别为 54.5%和 20%，P=0.0012）。TheraP cePSMA PET 阳性组患者的中位 PSA 无进展生存期（P=0.007）和 OS（P=0.0007）明显长于 TheraP cePSMA PET 阴性组。此外，TheraP cePSMA PET 阳性组是 OS 延长的显著预后因素（P=0.003）。对于符合 PSMA RLT 条件的患者，单一最热点病变的不同 SUV 阈值的应用对结果没有影响。根据 TheraP 的纳入标准选择 PSMA RLT 患者，导致我们预选患者队列的治疗反应和结果更好。然而，不符合这些标准的患者中有相当一部分也表现出了相当高的反应率。
