欧洲泌尿学协会的指南将177Lu PSMA-617前列腺特异性膜抗原（PSMA）配体作为转移性去势抵抗性前列腺癌（mCRPC）的治疗选择。临床实践中的一个重大挑战是基于可靠的预测性生物标志物追求个体化治疗方法。为评估177Lu PSMA在实际临床实践中的表现，并明确评估治疗反应的临床生物标志物，我们进行了一项回顾性观察性研究，纳入了8个欧洲高容量中心的233例mCRPC患者接受177Lu PSMA治疗。记录了基线特征和177Lu PSMA治疗期间和治疗后的临床参数。使用χ2检验和log-rank检验分析与治疗反应的相关性，并使用Mann-Whitney U检验计算具有和没有疾病进展的组之间的差异。使用Cox比例风险模型测量单变量和多变量调整风险比（HRs）。 在首次、第二次和第三次治疗周期后，观察到≥30%的前列腺特异性抗原（PSA）下降分别在41.7%，63.5%和77.8%的患者中。通过PSMA正电子发射计算机断层扫描定位技术重新分期，发现33.7%的患者存在基于影像的治疗反应，包括两例完全缓解，而13.4%的患者具有稳定疾病。进展的中位时间为5个月，连续抗肿瘤治疗开始的中位时间为8.5个月。而在第一、第二个177Lu PSMA治疗周期后，PSA下降≥30%（1个周期：p = 0.0003；2个周期：p = 0.004），第三个周期后的绝对PSA值（1个周期：p = 0.011；2个周期：p = 0.0005；3个周期：p = 0.002），以及PSA倍增时间 > 6个月（p = 0.009）与治疗反应显著相关。此外，177Lu PSMA治疗开始时的γ-谷氨酰转移酶≤31 U/L与没有脏器转移的患者的进展风险高出1.5倍（p = 0.046），但与有脏器转移的患者不相关。177Lu PSMA是mCRPC真实世界设定中的有效治疗选择。在前两个疗程后出现的PSA下降≥30%是一种早期治疗反应标志，可在临床实践中轻松应用。 177Lu PSMA是一种用于治疗晚期前列腺癌的放射性药物。我们回顾了八个欧洲中心的患者在临床试验之外使用177Lu PSMA的情况。我们发现，177Lu PSMA在实际临床实践中是一种有效的治疗选择。前两个疗程后的PSA（前列腺特异性抗原）下降≥30%是对治疗反应的早期指标，并可以用于个体化患者的治疗。 版权所有 © 2023 作者发表。由Elsevier B.V.出版。保留所有权利。

The European Association of Urology guidelines include the lutetium-177 (177Lu) PSMA-617 prostate-specific membrane antigen (PSMA) ligand as a therapy option for metastatic castration-resistant prostate cancer (mCRPC). A major challenge in clinical practice is to pursue a personalized treatment approach based on robust predictive biomarkers.To assess the performance of 177Lu PSMA in real-world practice and to elaborate clinical biomarkers for evaluating treatment responses.We conducted a retrospective observational study including 233 patients with mCRPC treated with 177Lu PSMA in eight high-volume European centers.Baseline characteristics and clinical parameters during and after 177Lu PSMA treatment were documented. Correlations to treatment response were analyzed using χ2 and log-rank tests, with differences between groups with and without disease progression calculated using a Mann-Whitney U test. Univariate and multivariate-adjusted hazard ratios (HRs) were measured using Cox proportional hazards models.A prostate-specific antigen (PSA) decrease of ≥30% was observed in 41.7%, 63.5%, and 77.8% of patients after the first, second, and third treatment cycle, respectively. Restaging performed via PSMA positron emission tomography-computed tomography revealed that 33.7% of patients had an imaging-based response, including two patients with a complete response, while 13.4% had stable disease. The median time to progression was 5 mo and the median time until the start of a consecutive antineoplastic therapy was 8.5 mo. Of importance, a PSA decrease ≥30% after the first two cycles of 177Lu PSMA (1 cycle: p = 0.0003; 2 cycles: p = 0.004), absolute PSA after the first three cycles (1 cycle: p = 0.011; 2 cycles: p = 0.0005; 3 cycles: p = 0.002), and a PSA doubling time >6 mo (p = 0.009) were significantly correlated to treatment response. Furthermore, gamma-glutamyl transferase ≤31 U/L at the start of 177Lu PSMA therapy was correlated with 1.5 times higher risk of progression for patients without but not with visceral metastases (p = 0.046).177Lu PSMA is an effective treatment option in mCRPC in the real-world setting. A PSA decrease ≥30% after the first two cycles is an early marker of response that can be easily implemented in clinical practice.177Lu PSMA is a radioactive agent approved for treatment of advanced prostate cancer. We reviewed its use outside of clinical trials for patients treated at eight European centers. We found that 177Lu PSMA is an effective treatment option in real-world practice. A PSA (prostate-specific antigen) decrease of ≥30% after the first two therapy cycles is an early indicator of response to treatment and can be used in personalizing treatments for patients.Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.