Increasing nerve-sparing radical prostatectomy rates using intraoperative nonlinear microscopy

使用术中非线性显微镜提高保留神经的根治性前列腺切除术率

• 批准号: 10343817
• 负责人: JAMES G FUJIMOTO
• 金额: $ 47.78万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-05 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10343817
• 关键词: Adoption; Agreement; Apical; Area; Blinded; Cancer Patient; Clinic; Clinical; Color; Consultations; Control Groups; Custom; Data; Decision Making; Development; Evaluation; Excision; Fluorescence; Formalin; Freezing; Frozen Sections; Hand; Histology; Hospitals; Human Resources; Image; Imaging Techniques; Impotence; Incontinence; Infrastructure; Institutes; Israel; Judgment; Lasers; Malignant Neoplasms; Malignant neoplasm of prostate; Massachusetts; Medical center; Methods; Microscopy; Microtome - medical device; Nerve; Nerve-Sparing Prostatectomy; Nuclear; Operative Surgical Procedures; Outcome; Paraffin Embedding; Pathologist; Pathology; Patients; Performance; Persons; Population; Postoperative Care; Postoperative Period; Preparation; Procedures; Prostate; Prostate Cancer therapy; Prostatectomy; Protocols documentation; Quality of life; Radical Prostatectomy; Randomized Controlled Trials; Reading; Recovery; Research Personnel; Residual Cancers; Robotics; Scanning; Screening for Prostate Cancer; Sex Functioning; Signal Transduction; Site; Specificity; Specimen; Stains; Surgeon; Surgical margins; Technology; Time; Tissues; arm; base; cost; cryostat; high resolution imaging; improved; instrument; male; medical schools; microscopic imaging; multidisciplinary; neurovascular; next generation; novel strategies; point of care; primary endpoint; programs; rapid technique; remote assessment; secondary endpoint; standard of care; tumor

Prostate cancer is the most common cancer in the US male population, with an estimated 160,000 new cases in 2018. Treatment with radical prostatectomy (RP), complete surgical excision of the prostate, results in favorable oncologic outcomes with long-term survival benefits. Nerve-sparing RP is favored if cancer does not involve the neurovascular bundles since patients have better recovery of sexual function and continence, major factors determining postoperative quality of life. However current preoperative methods do not accurately identify patients who could be treated by nerve-sparing RP. The NeuroSAFE study, Schlomm, et al., 2012 demonstrated that comprehensive intraoperative frozen section analysis (FSA) of margins near the neurovascular bundles increased the rate of nerve-sparing RPs. However comprehensive intraoperative FSA required extensive time and personnel, which is impractical for most hospitals. Nonlinear microscopy (NLM) can generate images of freshly excised tissue resembling H&E histology, without freezing or microtoming, reducing the time and labor required for pathology evaluation. We developed custom NLM technology and specimen handing/staining protocols for rapid, high-throughput evaluation of prostatectomy specimens. Our preliminary data demonstrates that NLM detects prostate cancer with 97% sensitivity and 100% specificity compared to formalin fixed paraffin embedded (FFPE) H&E in a study of 122 RP specimens from 40 patients with blinded reading by three pathologists. NLM promises to enable intraoperative evaluation of RP specimens with a simplified workflow that is practical for widespread clinical adoption. Our hypothesis is: NLM can be used to rapidly assess prostate surgical specimens and increase nerve-sparing RP rates without increasing positive margin rates. This is a collaborative, multidisciplinary program with investigators at the Massachusetts Institute of Technology and Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School. Aim 1 will develop next generation NLM technology and clinical workflow for rapid, comprehensive evaluation of prostate specimens in RP. These advances will enable a two person team (histotech/resident and pathologist) to perform comprehensive NLM of RP margins adjacent to the neurovascular bundles, faster and with much fewer personnel than NeuroSAFE. Aim 2 will perform a randomized controlled trial with patients undergoing robotic RP. The primary endpoints will be the rate of nerve-sparing RPs and rate of positive surgical margins in areas adjacent to the neurovascular bundles in a study group receiving intraoperative NLM margin assessment and standard-of-care postoperative FFPE histology versus a control group receiving standard-of-care FFPE postoperative histology. The secondary endpoints will be agreement between intraoperative NLM versus postoperative histology in the study arm and surgical times in the study arm versus control arm. Aim 3 will develop NLM technology and workflows that enable remote NLM evaluation which would increase access to pathologists with subspecialty expertise, streamline pathologist workflow, and facilitate adoption of intraoperative margin assessment in RP.

前列腺癌是美国男性人群中最常见的癌症，估计有 160,000 例新发病例 2018 年。采用根治性前列腺切除术 (RP) 进行治疗，即完全手术切除前列腺，结果 良好的肿瘤学结果和长期生存获益。如果癌症不治疗，则首选保留神经的 RP 涉及神经血管束，因为患者的性功能和节制能力恢复得更好，主要 决定术后生活质量的因素。然而目前的术前方法并不能准确识别 可以通过保留神经的 RP 治疗的患者。 Schlomm 等人 2012 年的 NeuroSAFE 研究证明 对神经血管束附近边缘进行综合术中冰冻切片分析 (FSA) 增加神经保留 RP 的比率。然而，全面的术中 FSA 需要大量时间 和人员，这对于大多数医院来说是不切实际的。非线性显微镜 (NLM) 可以生成以下图像 新鲜切除的组织类似于 H&E 组织学，无需冷冻或切片，减少了时间和劳动力 病理学评估所需。我们开发了定制 NLM 技术和样本处理/染色 前列腺切除标本的快速、高通量评估方案。我们的初步数据表明 与福尔马林固定石蜡相比，NLM 检测前列腺癌的灵敏度为 97%，特异性为 100% 将 (FFPE) H&E 嵌入到一项研究中，该研究涉及 40 名患者的 122 份 RP 标本，由 3 名患者进行盲读 病理学家。 NLM 承诺通过简化的工作流程实现 RP 标本的术中评估， 具有实用性，可广泛应用于临床。我们的假设是：NLM 可用于快速评估前列腺 手术标本并增加保留神经的 RP 率而不增加阳性切缘率。这是一个 与麻省理工学院和贝斯的研究人员合作的多学科项目 以色列女执事医疗中心 (BIDMC)、哈佛医学院。目标 1 将开发下一代 NLM 快速、全面评估 RP 中前列腺标本的技术和临床工作流程。这些 进展将使两人团队（组织技术人员/住院医生和病理学家）能够执行全面的 NLM RP 边缘邻近神经血管束，比 NeuroSAFE 更快且人员更少。 目标 2 将对接受机器人 RP 的患者进行随机对照试验。主要终点将 为保留神经的 RP 率和邻近神经血管区域的阳性手术切缘率 接受术中 NLM 切缘评估和术后标准护理的研究组中的束 FFPE 组织学与接受标准护理 FFPE 术后组织学的对照组相比。二级 研究组中术中 NLM 与术后组织学的终点将一致 研究组与对照组的手术时间。目标 3 将开发 NLM 技术和工作流程，使 远程 NLM 评估将增加获得具有亚专业知识的病理学家的机会，简化 病理学家工作流程，并促进在 RP 中采用术中切缘评估。