Schwinger Marcel, Kalogirou Charis, Scheper Vincent, Däuwel Maximiliane, Weber Simon, Seitz Anna Katharina, Kübler Hubert, Buck Andreas K, Werner Rudolf A, Hartrampf Philipp E
Department of Urology and Paediatric Urology, University Hospital Wuerzburg, Wuerzburg, Germany.
Department of Urology and Paediatric Urology, Julius-Maximilians University Medical Centre, Oberdürrbacher Str. 6, 97080, Würzburg, Germany.
Eur J Nucl Med Mol Imaging. 2025 Aug 25. doi: 10.1007/s00259-025-07519-1.
PURPOSE: We aimed to evaluate the safety and efficacy to explore predictors of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with [¹⁷⁷Lu]Lu-PSMA I&T in metastatic castration-resistant prostate cancer (mCRPC) patients aged ≥ 75 and explored baseline predictors of overall survival (OS). MATERIALS AND METHODS: 56 men (median age 78, range 75-95) were treated with RLT. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Baseline Gleason score, blood parameters (PSA, LDH), and sites of metastases (bone, lymph nodes, liver, lung) were recorded. Quantitative PET parameters such as SUVmean (mean standardized uptake value), SUVpeak (peak standardized uptake value), SUVmax (maximum standardized uptake value), PSMA-TV (PSMApositive tumor volume), TL-PSMA (total lesion PSMA) were measured. PET response was assessed by RECIP 1.0 (response evaluation criteria in PSMA imaging); biochemical response by PCWG3 (prostate cancer working group 3). Associations with OS were analyzed via uni- and multivariable Cox regression and Kaplan-Meier curves. RESULTS: No CTCAE grade III-V toxicities occurred. Grade I/II hematologic events included anemia (23.2%), leukocytopenia (18.6%) and thrombocytopenia (9.3%); eGFR declined by 2.5% (grade I/II in 18.6%). Median OS was 11 months; 60.7% of patients died. 74.4% of patients (32/43) showed PSA declines (median - 58%; 14/43 ≥ 50%). Higher baseline PSA (HR 1.001 per ng/mL; P < 0.10) and LDH (HR 1.008 per U/L; P < 0.01) were associated with shorter OS. Patients with progressive disease by both RECIP and PCWG3 had shorter OS than others (11 vs. 22 months; HR 3.3; P < 0.01). Any PSA response predicted longer OS (21 vs. 7 months; HR 0.3; P < 0.01). Presence of liver metastases portended poorer survival (8 vs. 21 months; HR 6.7; P < 0.001). CONCLUSION: [¹⁷⁷Lu]Lu-PSMA I&T RLT is well tolerated in patients ≥ 75 years. Lower baseline PSA and LDH but not PSMA-TV predict longer OS. Early PSA response strongly correlates with improved survival. Combined use of RECIP and PCWG3 criteria optimizes response assessment.
目的：我们旨在评估使用[¹⁷⁷Lu]Lu - PSMA I&T进行前列腺特异性膜抗原（PSMA）靶向放射性配体治疗（RLT）对年龄≥75岁的转移性去势抵抗性前列腺癌（mCRPC）患者的安全性和疗效，并探索总生存期（OS）的基线预测因素。 材料与方法：56名男性（中位年龄78岁，范围75 - 95岁）接受了RLT治疗。不良事件根据不良事件通用术语标准（CTCAE）v5.0进行分级。记录基线Gleason评分、血液参数（PSA、LDH）以及转移部位（骨、淋巴结、肝、肺）。测量定量PET参数，如SUVmean（平均标准化摄取值）、SUVpeak（峰值标准化摄取值）、SUVmax（最大标准化摄取值）、PSMA-TV（PSMA阳性肿瘤体积）、TL-PSMA（总病灶PSMA）。通过RECIP 1.0（PSMA成像中的反应评估标准）评估PET反应；通过PCWG3（前列腺癌工作组3）评估生化反应。通过单变量和多变量Cox回归以及Kaplan-Meier曲线分析与OS的关联。 结果：未发生CTCAE III - V级毒性反应。I/II级血液学事件包括贫血（23.2%）、白细胞减少（18.6%）和血小板减少（9.3%）；估算肾小球滤过率（eGFR）下降2.5%（I/II级为18.6%）。中位OS为11个月；60.7%的患者死亡。74.4%的患者（32/43）PSA下降（中位下降 - 58%；14/43≥50%）。较高的基线PSA（每ng/mL的HR为1.001；P < 0.10）和LDH（每U/L的HR为1.008；P < 0.01）与较短的OS相关。根据RECIP和PCWG3标准均出现疾病进展的患者OS比其他患者短（11个月对22个月；HR 3.3；P < 0.01）。任何PSA反应均预示着较长的OS（21个月对7个月；HR 0.3；P < 0.01）。存在肝转移预示着较差的生存期（8个月对21个月；HR 6.7；P < 0.001）。 结论：[¹⁷⁷Lu]Lu - PSMA I&T RLT在≥75岁的患者中耐受性良好。较低的基线PSA和LDH而非PSMA-TV可预测较长的OS。早期PSA反应与生存期改善密切相关。联合使用RECIP和PCWG3标准可优化反应评估。
Eur J Nucl Med Mol Imaging. 2025-8-25
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