PSMA-PET to Guide Prostatectomy: Can PSMA-PET Appropriately Modify Surgery, Reduce Nerve Damage and Optimize Quality-of-Life?

项目摘要/摘要 68Ga-P16-093放射性药物是一种针对前列腺特异膜的研究药物 抗原(PSMA)，它在大多数前列腺癌中高度表达。PSMA-PET尚未被验证为 指导手术切除原发性前列腺癌的工具。 此二期临床试验的目标是严格测试68Ga-P16-093PET识别额外肿瘤的能力。 前列腺癌的前列腺延展，以指导手术切除，提高术后患者的生存质量 生活质量。对于需要前列腺切除术的前列腺癌患者，我们假设PSMA-PET 这些发现将准确地区分哪些患者可以安全地接受神经保留和/或肌肉保留 从那些更积极的广泛切除对癌症控制至关重要的人那里进行手术；因此，优化 生活质量结果。因此，该项目有两个相辅相成但独立的具体目标： 目的1.测量68Ga-P16-093PET-CT和常规护理标准的准确性 MpMRI，用于术前检测前列腺外延。 目的2.衡量治疗改进和患者生活质量结果，这些结果是由68Ga- P16-093-PET纳入手术计划。 本项目的创新之处在于将该成像技术应用于手术前的治疗。 新诊断疾病的计划；随机外科手术中对药剂性能的最终评估 对照试验；以及影像对手术计划和随后的影响的详细评估 患者的临床结果。作为对照组，一半登记的受试者将接受他们的护理标准 只有多参数磁共振成像和活检结果支持的手术计划的前列腺切除术。另一个 一半的受试者将随机接受68Ga-P16-093PET/CT的手术前盆腔成像 用于对疾病的位置和程度进行独立评估。放射学MRI和PET读取器将是 对另一种方式的结果视而不见。外科医生将收到所有成像的报告，但必须 在收到正电子发射计算机断层扫描结果之前，记录一份标准护理手术计划。然后外科医生将记录 PET信息是否以及如何修改他们先前的手术计划。为了验证成像发现， 整体病理学将成为描述疾病特征的“黄金标准”。病人结局 将在手术后18个月内对措施和癌症复发进行跟踪。我们的初步研究 提示68Ga-P16-093PET-CT对前列腺外病变的诊断准确率高于mpMRI 分机。而且，PET引导的手术改进通常会导致适当的保存 神经和肌肉的作用，从而改善许多患者治疗后的生活质量，同时也有助于 避免手术切缘呈阳性。

Project Summary/Abstract The 68Ga-P16-093 radiopharmaceutical is an investigational agent that targets prostate specific membrane antigen (PSMA), which is highly expressed in most prostate cancers. PSMA-PET has not been validated as a tool for guiding surgical resection of primary prostate cancer. The objective of this Phase II Clinical Trial is to critically test the ability of 68Ga-P16-093 PET to identify extra- prostatic extension of prostate cancer, to guide surgical resection, and to improve the patient’s post-surgical quality-of-life. For prostate cancer patients who require prostatectomy, we hypothesize that PSMA-PET findings will accurately differentiate patients who can safely undergo nerve-sparing and/or muscle-sparing surgery from those in whom more aggressive wide resection is essential for cancer control; thus, optimizing quality-of-life outcomes. Therefore, the project has two complementary yet independent Specific Aims: Aim 1. To measure the accuracy of both 68Ga-P16-093 PET-CT, and conventional standard-of-care mpMRI, for presurgical detection of extra-prostatic extension. Aim 2. To measure treatment modifications, and patient quality-of-life outcomes, that result from 68Ga- P16-093 -PET incorporation into surgical planning. The innovations of this project are the application of this imaging technology in pre-surgical treatment planning for newly diagnosed disease; the definitive assessment of agent performance in a surgical randomized controlled trial; and the detailed assessments of imaging impact on both surgical planning and subsequent patient clinical outcome. As a control group, one-half of the enrolled subjects will receive their standard-of-care prostatectomy with surgical planning supported only by multiparametric MRI and biopsy findings. The other half of the subjects will be randomized to also receive pre-surgical pelvic imaging with 68Ga-P16-093 PET/CT for independent assessment of the location and extent of disease. The radiology MRI and PET readers will be blinded to the findings of the other modality. The surgeon will receive reports on all imaging, but must document a standard-of-care surgical plan before receiving the PET findings. The surgeon will then document whether, and how, the PET information modifies their prior surgical plan. For validation of imaging findings, whole mount pathology will serve as the “gold standard” for characterization of disease. Patient outcome measures, and cancer recurrence, will be tracked for 18-months following surgery. Our preliminary studies indicate 68Ga-P16-093 PET-CT will show higher accuracy than mpMRI for detection of extra-prostatic extension. And, that the PET-directed surgical modifications will frequently result in appropriate preservation of nerves and muscle, thereby improving post-treatment quality-of-life for many patients, while also helping to avoid positive surgical margins.