治疗前估计肾小球滤过率可预测接受 PSMA 靶向放射性配体治疗的患者发生慢性肾脏病。

Pretherapeutic estimated glomerular filtration rate predicts development of chronic kidney disease in patients receiving PSMA-targeted radioligand therapy.

机构信息

Department of Nuclear Medicine Medical School Hannover, Hannover, Germany.

出版信息

Prostate. 2022 Jan;82(1):86-96. doi: 10.1002/pros.24250. Epub 2021 Oct 11.

DOI:10.1002/pros.24250

PMID:34633090

Abstract

BACKGROUND

Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) may be associated with renal toxicity. We aimed to identify predictive parameters for the development of chronic kidney disease (CKD) in patients with metastatic castration resistant prostate cancer (mCRPC) undergoing RLT.

METHODS

In 46 mCRPC patients scheduled for Lu-177-PSMA-RLT, pretherapeutic estimated glomerular filtration rate (eGFR [ml/min/1.73 m ]), Tc-99m-mercaptoacetyltriglycine (Tc-99m-MAG3) clearance and baseline Ga-68-PSMA-ligand positron emission tomography (PET)-derived renal cortical uptake and PSMA-tumor volume (TV) were determined. We tested the predictive capability of these parameters and clinical risk factors for the occurrence of CKD (defined as CTCAE vers. 5.0 grade 2 or higher) during follow-up.

RESULTS

After 4 ± 3 cycles of RLT average eGFR declined from 76 ± 17 to 72 ± 20 ml/min/1.73 m (p = 0.003). Increased estimated renal radiation dose (eRRD) was significantly associated with renal functional decline (p = 0.008). During follow-up, 16/46 (30.4%) developed CKD grade 2 (no grade 3 or higher). In receiver operating characteristic (ROC) analysis, pretherapeutic eGFR was highly accurate in identifying the occurrence of CKD vs no CKD with an area under the curve (AUC) of 0.945 (p < 0.001; best threshold, 77 ml/min/1.73 m ), followed by Tc-99m-MAG3-derived tubular extraction rate (TER; AUC, 0.831, p < 0.001; best threshold, 200 ml/min/1.73 m ). Renal PET signal (p = 0.751) and PSMA-TV (p = 0.942), however, were not predictive. Kaplan-Meier analyses revealed adverse renal outcome for patients with lower eGFR (p = 0.001) and lower scintigraphy-derived TER (p = 0.009), with pretherapeutic eGFR emerging as the sole predictive parameter in multivariate analysis (p = 0.007).

CONCLUSION

Serious adverse renal events are not a frequent phenomenon after PSMA-targeted RLT. However, in patients developing moderate CKD after RLT, pretherapeutic eGFR is an independent predictor for renal impairment during follow-up.

摘要

背景

前列腺特异性膜抗原（PSMA）靶向放射性配体治疗（RLT）可能与肾毒性有关。我们旨在确定接受 Lu-177-PSMA-RLT 的转移性去势抵抗性前列腺癌（mCRPC）患者发生慢性肾脏病（CKD）的预测参数。

方法

在 46 名计划接受 Lu-177-PSMA-RLT 的 mCRPC 患者中，测定治疗前估算肾小球滤过率（eGFR [ml/min/1.73 m]）、Tc-99m-巯基乙酰三甘氨酸（Tc-99m-MAG3）清除率以及 Ga-68-PSMA-配体正电子发射断层扫描（PET）衍生的肾皮质摄取和 PSMA-肿瘤体积（TV）。我们测试了这些参数和临床危险因素对随访期间 CKD（定义为 CTCAE 版本 5.0 等级 2 或更高）发生的预测能力。

结果

在接受 4±3 个周期的 RLT 后，平均 eGFR 从 76±17 降至 72±20 ml/min/1.73 m（p=0.003）。估计的肾辐射剂量（eRRD）增加与肾功能下降显著相关（p=0.008）。在随访期间，16/46（30.4%）发生 CKD 2 级（无 3 级或更高）。在受试者工作特征（ROC）分析中，治疗前 eGFR 高度准确地识别出 CKD 的发生与无 CKD，曲线下面积（AUC）为 0.945（p<0.001；最佳阈值为 77 ml/min/1.73 m），其次是 Tc-99m-MAG3 衍生的管状提取率（TER；AUC，0.831，p<0.001；最佳阈值，200 ml/min/1.73 m）。然而，肾 PET 信号（p=0.751）和 PSMA-TV（p=0.942）没有预测价值。Kaplan-Meier 分析显示，eGFR 较低（p=0.001）和闪烁显像衍生的 TER 较低（p=0.009）的患者肾脏不良结局，在多变量分析中，治疗前 eGFR 是唯一的预测参数（p=0.007）。