Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, 200 Medical Plaza, Suite B114-61, Los Angeles, CA, 90095, USA.
Department of Nuclear Medicine, Technical University Munich, Klinikum Rechts Der Isar, Munich, Germany.
Eur J Nucl Med Mol Imaging. 2022 Oct;49(12):4271-4281. doi: 10.1007/s00259-022-05882-x. Epub 2022 Jun 29.
To compare the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the adapted Prostate Cancer Working Group Criteria 3 (aPCWG3), the adapted Positron Emission Tomography Response Criteria in Solid Tumors (aPERCIST), the PSMA PET Progression (PPP), and the Response Evaluation Criteria In PSMA-Imaging (RECIP) 1.0 for response evaluation using prostate-specific membrane antigen (PSMA)-PET/CT in men with metastatic castration-resistant prostate cancer (mCRPC) treated with Lu-PSMA radioligand therapy.
A total of 124 patients were included in this multicenter retrospective study. All patients received Lu-PSMA and underwent PSMA-PET/CT scans at baseline (bPET) and at 12 weeks (iPET). Imaging responses according to RECIST 1.1, aPCWG3, aPERCIST, PPP, and RECIP 1.0 were interpreted by consensus among three blinded readers. Changes in total tumor burden were obtained using the semi-automatic qPSMA software. The response according to each criterion was classified to progressive disease (PD) vs no-PD. Primary outcome measure was the prognostic value (by Cox regression analysis) for overall survival (OS). Secondary outcome measure was the inter-reader reliability (by Cohen's κ coefficient).
A total of 43 (35%) of patients had non-measurable disease according to RECIST 1.1. Sixteen (13%), 66 (52%), 72 (58%), 69 (56%), and 39 (32%) of 124 patients had PD according to RECIST 1.1, aPCWG3, aPERCIST, PPP, and RECIP, respectively. PD vs no-PD had significantly higher risk of death according to aPCWG3 (HR = 2.37; 95%CI, 1.62-3.48; p < 0.001), aPERCIST (HR = 2.48; 95%CI, 1.68-3.66; p < 0.001), PPP (HR = 2.72; 95%CI, 1.85-4.01; p < 0.001), RECIP 1.0 (HR = 4.33; 95%CI, 2.80-6.70; p < 0.001), but not according to RECIST 1.1 (HR = 1.29; 95%CI, 0.73-2.27; p = 0.38). The κ index of RECIST 1.1, aPCWG3, aPERCIST 1.0, PPP, and RECIP 1.0 for identifying PD vs no-PD were 0.50 (95%CI, 0.32-0.76), 0.72 (95%CI, 0.63-0.82), 0.68 (95%CI, 0.63-0.73), 0.73 (95%CI, 0.63-0.83), and 0.83 (95%CI, 0.77-0.88), respectively.
PSMA-PET-specific criteria for early response evaluation in men with mCRPC treated with Lu-PSMA achieved higher prognostic values and inter-reader reliabilities in comparison to conventional CT assessment or to criteria adapted to PSMA-PET from other imaging modalities. RECIP 1.0 identified the fewest patients with PD and achieved the highest risk of death for PD vs. no-PD, suggesting that other classification methods tend to overcall progression. Prospective validation of our findings on an independent patient cohort is warranted.
比较 1.1 版实体瘤反应评估标准（RECIST）、前列腺癌工作组适应性标准 3（aPCWG3）、正电子发射断层扫描实体瘤适应性反应标准（aPERCIST）、前列腺特异性膜抗原（PSMA）PET 进展（PPP）和 PSMA 成像适应性反应评估标准 1.0（RECIP 1.0），以评估接受 Lu-PSMA 放射性配体治疗的转移性去势抵抗性前列腺癌（mCRPC）男性患者中 PSMA-PET/CT 的反应。
本多中心回顾性研究共纳入 124 例患者。所有患者均接受 Lu-PSMA 治疗，并在基线（bPET）和 12 周（iPET）时进行 PSMA-PET/CT 扫描。三位盲法读者通过共识对 RECIST 1.1、aPCWG3、aPERCIST、PPP 和 RECIP 1.0 进行了影像学反应的解读。使用半自动 qPSMA 软件获得总肿瘤负荷的变化。根据每个标准的反应分为进展性疾病（PD）与非 PD。主要观察指标是总生存（OS）的预后价值（通过 Cox 回归分析）。次要观察指标是读者间的可靠性（通过 Cohen's κ 系数）。
根据 RECIST 1.1，共有 43 例（35%）患者为不可测量疾病。根据 RECIST 1.1、aPCWG3、aPERCIST、PPP 和 RECIP，分别有 16 例（13%）、66 例（52%）、72 例（58%）、69 例（56%）和 39 例（32%）的患者为 PD。根据 aPCWG3（HR=2.37；95%CI，1.62-3.48；p<0.001）、aPERCIST（HR=2.48；95%CI，1.68-3.66；p<0.001）、PPP（HR=2.72；95%CI，1.85-4.01；p<0.001）、RECIP 1.0（HR=4.33；95%CI，2.80-6.70；p<0.001），PD 与非 PD 的死亡风险显著增加，但根据 RECIST 1.1 无显著差异（HR=1.29；95%CI，0.73-2.27；p=0.38）。根据 RECIST 1.1、aPCWG3、aPERCIST 1.0、PPP 和 RECIP 1.0 对 PD 与非 PD 的识别，κ 指数分别为 0.50（95%CI，0.32-0.76）、0.72（95%CI，0.63-0.82）、0.68（95%CI，0.63-0.73）、0.73（95%CI，0.63-0.83）和 0.83（95%CI，0.77-0.88）。
与常规 CT 评估或其他 PSMA-PET 成像方式的适应性标准相比，用于 Lu-PSMA 治疗的 mCRPC 男性早期反应评估的 PSMA-PET 特异性标准在预后价值和读者间可靠性方面均有较高的表现。RECIP 1.0 确定的 PD 患者最少，且 PD 与非 PD 相比，死亡风险最高，提示其他分类方法往往会高估进展。需要在独立的患者队列中对我们的研究结果进行前瞻性验证。
