Purpose

In patients with metastatic castration-resistant prostate cancer (mCRPC) treated with prostate-specific membrane antigen-targeted radioligand therapy (PSMA-RLT), the predictive value of PSMA PET/CT-derived response is still under investigation. Early molecular imaging response based on total viable tumor burden and its association with overall survival (OS) was explored in this study.

Methods

Sixty-six mCRPC patients who received [¹⁷⁷Lu]Lu-PSMA-617 RLT within a prospective patient registry (REALITY Study, NCT04833517) were analyzed. Patients received a [⁶⁸Ga]Ga-PSMA-11 PET/CT scan before the first and after the second cycle of PSMA-RLT. Total lesion PSMA (TLP) was determined by semiautomatic whole-body tumor segmentation. Molecular imaging response was assessed by change in TLP and modified PERCIST criteria. Biochemical response was assessed using standard serum PSA and PCWG3 criteria. Both response assessment methods and additional baseline parameters were analyzed regarding their association with OS by univariate and multivariable analysis.

Results

By molecular imaging, 40/66 (60.6%) patients showed partial remission (PR), 19/66 (28.7%) stable disease (SD), and 7/66 (10.6%) progressive disease (PD). Biochemical response assessment revealed PR in 34/66 (51.5%) patients, SD in 20/66 (30.3%), and PD in 12/66 (18.2%). Response assessments were concordant in 49/66 (74.3%) cases. On univariate analysis, both molecular and biochemical response (p = 0.001 and 0.008, respectively) as well as two baseline characteristics (ALP and ECOG) were each significantly associated with OS. The median OS of patients showing molecular PR was 24.6 versus 10.7 months in the remaining patients (with SD or PD). On multivariable analysis molecular imaging response remained an independent predictor of OS (p = 0.002), eliminating biochemical response as insignificant (p = 0.515).

Conclusion

The new whole-body molecular imaging–derived biomarker, early change of total lesion PSMA (TLP), independently predicts overall survival in [¹⁷⁷Lu]Lu-PSMA-617 RLT in mCRPC, outperforming conventional PSA-based response assessment. TLP might be considered a more distinguished and advanced biomarker for monitoring PSMA-RLT over commonly used serum PSA.

中文翻译：

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基于 [68Ga]Ga-PSMA-11 PET/CT 中总活肿瘤负荷测定的早期分子成像反应评估独立预测 [177Lu]Lu-PSMA-617 放射配体治疗的总生存期

目的

在接受前列腺特异性膜抗原靶向放射性配体治疗 (PSMA-RLT) 治疗的转移性去势抵抗性前列腺癌 (mCRPC) 患者中，PSMA PET/CT 衍生反应的预测价值仍在研究中。本研究探讨了基于总存活肿瘤负荷的早期分子成像反应及其与总生存期 (OS) 的关联。

方法

分析了在前瞻性患者登记（REALITY 研究，NCT04833517）中接受 [ ^{177 Lu]Lu-PSMA-617 RLT 的 66 名 mCRPC 患者。}患者在 PSMA-RLT 的第一个周期之前和第二个周期之后接受了 [ ^{68 Ga]Ga-PSMA-11 PET/CT 扫描。}通过半自动全身肿瘤分割确定总病变 PSMA (TLP)。通过 TLP 的变化和修改的 PERCIST 标准评估分子成像反应。使用标准血清 PSA 和 PCWG3 标准评估生化反应。通过单变量和多变量分析分析了反应评估方法和其他基线参数与 OS 的关联。

结果

通过分子成像，40/66 (60.6%) 患者显示部分缓解 (PR)，19/66 (28.7%) 疾病稳定 (SD) 和 7/66 (10.6%) 疾病进展 (PD)。生化反应评估显示 34/66 (51.5%) 患者为 PR，20/66 (30.3%) 患者为 SD，12/66 (18.2%) 患者为 PD。在 49/66 (74.3%) 的病例中，反应评估是一致的。在单变量分析中，分子和生化反应（分别为p  = 0.001 和 0.008）以及两个基线特征（ALP 和 ECOG）均与 OS 显着相关。显示分子 PR 的患者的中位 OS 为 24.6 个月，而其余患者（患有 SD 或 PD）的中位 OS 为 10.7 个月。在多变量分析中，分子成像反应仍然是 OS 的独立预测因子（p = 0.002），消除生化反应微不足道（p  = 0.515）。

结论

新的全身分子成像衍生的生物标志物，即总病变 PSMA (TLP) 的早期变化，独立预测 mCRPC 中 [ ¹⁷⁷ Lu]Lu-PSMA-617 RLT 的总体存活率，优于传统的基于 PSA 的反应评估。TLP 可能被认为是监测 PSMA-RLT 优于常用血清 PSA 的更显着和先进的生物标志物。