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

项目概要/摘要 68 Ga-P16 -093放射性药物是一种靶向前列腺特异性膜的研究药物 前列腺特异性抗原（PSMA）在大多数前列腺癌中高度表达。PSMA-PET尚未被确认为 用于指导原发性前列腺癌手术切除的工具。 本II期临床试验的目的是严格测试68 Ga-P16 -093 PET识别额外 前列腺癌的前列腺延伸，以指导手术切除，并提高患者的术后 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 研究结果将准确区分可以安全接受神经保留和/或肌肉保留的患者 手术从那些更积极的广泛切除是必要的癌症控制;因此，优化 生活质量的结果。因此，该项目有两个互补但独立的具体目标： 目标1。测量68 Ga-P16 -093 PET-CT和传统标准治疗的准确度 mpMRI，用于前列腺外延伸的术前检测。 目标二。为了测量68 Ga导致的治疗调整和患者生活质量结局， P16-093 -将PET纳入手术计划。 本项目的创新之处在于将这种成像技术应用于术前治疗 计划新诊断的疾病;在手术随机化中对药物性能的明确评估 对照试验;以及详细评估成像对手术计划和随后的 患者临床结局。作为对照组，一半入组受试者将接受标准治疗 只有多参数MRI和活检结果支持的手术计划下的直肠癌切除术。另 一半受试者将随机接受术前盆腔68 Ga-P16 -093 PET/CT成像 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 对另一种方式的结果不知情。外科医生将收到所有成像报告，但必须 在接收PET结果之前，记录标准护理手术计划。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。为了验证成像结果， 整体病理学将作为疾病表征的“金标准”。患者结局 手术后18个月内，将对这些措施和癌症复发情况进行跟踪。我们的初步研究 表明68 Ga-P16 -093 PET-CT在检测前列腺外病变方面显示出比mpMRI更高准确性 扩展名.并且，PET指导的手术修改通常会导致适当的保存 神经和肌肉，从而改善许多患者的治疗后生活质量，同时也有助于 避免手术切缘阳性。

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.