F-rhPSMA-7.3正电子发射断层扫描在疑似前列腺癌复发男性中的诊断性能和安全性：一项3期前瞻性多中心研究（SPOTLIGHT）的结果

Diagnostic Performance and Safety of F-rhPSMA-7.3 Positron Emission Tomography in Men With Suspected Prostate Cancer Recurrence: Results From a Phase 3, Prospective, Multicenter Study (SPOTLIGHT).

作者信息

Jani Ashesh B, Ravizzini Gregory C, Gartrell Benjamin A, Siegel Barry A, Twardowski Przemyslaw, Saltzstein Daniel, Fleming Mark T, Chau Albert, Davis Phillip, Chapin Brian F, Schuster David M

机构信息

Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia.

Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

出版信息

J Urol. 2023 Aug;210(2):299-311. doi: 10.1097/JU.0000000000003493. Epub 2023 Apr 26.

DOI:10.1097/JU.0000000000003493

PMID:37126069

Abstract

PURPOSE

SPOTLIGHT (NCT04186845) evaluated diagnostic performance and safety of radiohybrid F-rhPSMA-7.3, a novel high-affinity positron emission tomography radiopharmaceutical.

MATERIALS AND METHODS

Men with prostate cancer recurrence underwent positron emission tomography/CT 50-70 minutes after intravenous administration of 296±20% MBq F-rhPSMA-7.3. To assess the coprimary end points (verified detection rate and combined region-level positive predictive value), 3 blinded, independent central readers evaluated the scans. Verified detection rate is equivalent to the overall detection rate × positive predictive value. Standard of truth was established for each patient using histopathology or confirmatory imaging. Statistical thresholds (lower bounds of the confidence intervals) of 36.5% and 62.5% were prespecified for verified detection rate and combined region-level positive predictive value, respectively Additional end points included detection rate, verified detection rate, and combined region-level positive predictive value in patients with histopathology standard of truth, and safety.

RESULTS

The overall F-rhPSMA-7.3 detection rate among all 389 patients with an evaluable scan was 83% (majority read). Among the 366 patients (median prostate-specific antigen 1.27 ng/mL) for whom a standard of truth (histopathology [n=69]/confirmatory imaging only [n=297]) was available, verified detection rate ranged from 51% (95% CI 46.1-56.6) to 54% (95% CI 48.8-59.3), exceeding the prespecified statistical threshold. Combined region-level positive predictive value ranged from 46% (95% CI 42.0-50.3) to 60% (95% CI 55.1-65.5) across the readers, not meeting the threshold. In the subset of patients with histopathology standard of truth, the verified detection rate and combined region-level positive predictive value were both above the prespecified thresholds (majority read, 81% [95% CI 69.9-89.6] and 72% [95% CI 62.5-80.7], respectively). No significant safety concerns were identified.

CONCLUSIONS

F-rhPSMA-7.3 offers a clinically meaningful verified detection rate for localization of recurrent prostate cancer. Despite missing the coprimary end point of combined region-level positive predictive value, the totality of the data support the potential clinical utility of F-rhPSMA-7.3.

摘要

目的

SPOTLIGHT（NCT04186845）评估了新型高亲和力正电子发射断层扫描放射性药物放射性杂交体F-rhPSMA-7.3的诊断性能和安全性。

材料与方法

前列腺癌复发的男性患者在静脉注射296±20% MBq F-rhPSMA-7.3后50 - 70分钟接受正电子发射断层扫描/计算机断层扫描。为评估共同主要终点（验证检测率和联合区域水平阳性预测值），3名盲法、独立的中心阅片者对扫描结果进行评估。验证检测率相当于总体检测率×阳性预测值。使用组织病理学或确证性影像学为每位患者确立真值标准。验证检测率和联合区域水平阳性预测值的统计阈值（置信区间下限）分别预先设定为36.5%和62.5%。其他终点包括具有组织病理学真值标准的患者的检测率、验证检测率和联合区域水平阳性预测值，以及安全性。

结果

在所有389例可评估扫描的患者中，F-rhPSMA-7.3的总体检测率为83%（多数阅片结果）。在366例患者（前列腺特异性抗原中位数为1.27 ng/mL）中，有真值标准（组织病理学[n = 69]/仅确证性影像学[n = 297]），验证检测率在51%（95% CI 46.1 - 56.6）至54%（95% CI 48.8 - 59.3）之间，超过预先设定的统计阈值。阅片者间联合区域水平阳性预测值在46%（95% CI 42.0 - 50.3）至60%（95% CI 55.1 - 65.5）之间，未达到阈值。在具有组织病理学真值标准的患者亚组中，验证检测率和联合区域水平阳性预测值均高于预先设定的阈值（多数阅片结果，分别为81%[95% CI 69.9 - 89.6]和72%[95% CI 62.5 - 80.7]）。未发现明显的安全问题。