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 Mar;64(3):402-409. doi: 10.2967/jnumed.122.264402. Epub 2022 Sep 22.
The aim of this retrospective analysis was to determine prostate-specific antigen (PSA) response, PSA progression-free survival (PFS), and overall survival (OS) in a large cohort of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with Lu-PSMA-I&T and to identify clinical and scintigraphic prognostic factors for outcome. In total, 301 consecutive mCRPC patients were included in this analysis. Prognostic factors included clinical parameters, routine laboratory parameters, and findings on posttreatment scintigraphy. Scintigraphic tumor uptake of Lu-PSMA-I&T was compared with salivary gland uptake and classified as high or low. The longest extent of skeletal metastatic disease was measured, and its changes during therapy were used to define scintigraphic progression, response, and stable disease. A PSA response of at least 50%, PSA PFS, and OS were calculated. In total, 1,138 cycles (median, 3 cycles per patient) of Lu-PSMA-I&T using a standard activity of 7.4 GBq were applied intravenously every 4-10 wk (median, 6 wk). Overall, 34% (95% CI, 28%-38%) of patients showed a PSA response of at least 50%, and the median PSA PFS and OS of the total patient cohort were 16.0 wk (95% CI, 12.1-19.9) and 13.8 mo (95% CI, 12.4-15.5), respectively. Patients with high scintigraphic tumor uptake showed a higher PSA response rate of at least 50% (45.7% vs. 10.4%; < 0.0001) and a significantly reduced risk of PSA progression (median event time, 24.9 vs. 9.0 wk; hazard ratio, 0.3; 95% CI, 0.2-0.5; < 0.0001). In our data, risk of death was not significantly different between patients with high scintigraphic uptake and those with low scintigraphic uptake (median, 14.4 vs. 12.4 mo; hazard ratio, 0.9; 95% CI, 0.6-1.3; = 0.6). In a multivariable analysis, the following pretherapeutic prognostic factors for OS were identified: alkaline phosphatase, lactate dehydrogenase, and PSA levels; prior chemotherapy; and the presence of visceral metastases. Scintigraphic response was a strong prognostic factor for PSA response, PSA PFS, and OS after 1 treatment cycle. This retrospective analysis of a large group of consecutive patients corroborates previous clinical experience for Lu-PSMA-I&T in mCRPC and establishes previously proposed prognostic factors. The skeletal tumor extent and its changes were identified as new potential biomarkers to predict the outcome of therapy after the first treatment cycle.
这项回顾性分析的目的是确定接受 Lu-PSMA-I&T 治疗的转移性去势抵抗性前列腺癌（mCRPC）患者中前列腺特异性抗原（PSA）的反应、PSA 无进展生存期（PFS）和总生存期（OS），并确定与结果相关的临床和闪烁扫描预后因素。 总共纳入了 301 例连续的 mCRPC 患者进行了这项分析。预后因素包括临床参数、常规实验室参数以及治疗后闪烁扫描的结果。Lu-PSMA-I&T 的闪烁扫描肿瘤摄取与唾液腺摄取进行了比较，并分为高或低。测量最长的骨骼转移性疾病程度，并使用其在治疗过程中的变化来定义闪烁扫描进展、反应和稳定疾病。计算至少 50%的 PSA 反应、PSA PFS 和 OS。 总共静脉内应用了 301 例（中位数，3 个周期/例）标准活度为 7.4GBq 的 Lu-PSMA-I&T，每 4-10 周（中位数，6 周）一次。总体而言，34%（95%CI，28%-38%）的患者出现了至少 50%的 PSA 反应，总患者队列的中位 PSA PFS 和 OS 分别为 16.0 周（95%CI，12.1-19.9）和 13.8 个月（95%CI，12.4-15.5）。摄取高闪烁扫描肿瘤的患者具有更高的至少 50%的 PSA 反应率（45.7%比 10.4%；<0.0001）和 PSA 进展的风险显著降低（中位事件时间，24.9 比 9.0 周；风险比，0.3；95%CI，0.2-0.5；<0.0001）。在我们的数据中，摄取高闪烁扫描肿瘤和摄取低闪烁扫描肿瘤的患者的死亡风险没有显著差异（中位数，14.4 比 12.4 个月；风险比，0.9；95%CI，0.6-1.3；=0.6）。在多变量分析中，确定了以下与 OS 相关的预测因素：碱性磷酸酶、乳酸脱氢酶和 PSA 水平；先前的化疗；以及是否存在内脏转移。闪烁扫描反应是 PSA 反应、PSA PFS 和第 1 个治疗周期后 OS 的强烈预后因素。 这项对大量连续患者的回顾性分析证实了 Lu-PSMA-I&T 在 mCRPC 中的先前临床经验，并建立了先前提出的预后因素。骨骼肿瘤程度及其变化被确定为预测首次治疗后治疗结果的新的潜在生物标志物。
