Increasing nerve-sparing radical prostatectomy rates using intraoperative nonlinear microscopy

前列腺癌是美国男性中最常见的癌症，估计有16万新病例 2018年。根治性前列腺切除术(RP)是一种完全切除前列腺的手术，其结果是 良好的肿瘤学结果，对长期生存有利。如果癌症不保留神经，保留神经的RP是受欢迎的 涉及神经血管束，因为患者的性功能和大小便失禁恢复较好 影响术后生活质量的因素。然而，目前的术前方法并不能准确地识别 可行保留神经根治术的患者。Schlomm等人2012年的NeuroSAFE研究证明 术中对神经血管束附近边缘的全面冰冻切片分析 增加了保留神经的RPS的比率。然而，全面的术中FSA需要大量的时间 和人员，这对大多数医院来说是不切实际的。非线性显微镜(NLM)可以产生 新鲜切除的组织与HE组织学相似，无需冷冻或显微切割，减少了时间和劳动力 病理评估所需的。我们开发了定制的NLM技术和标本处理/染色 用于快速、高通量评估前列腺切除标本的方案。我们的初步数据显示 与福尔马林固定石蜡相比，NLM检测前列腺癌的敏感性和特异性分别为97%和100% 包埋(FFPE)H&E在40例盲读患者122例RP标本中的研究 病理学家。NLM承诺通过简化的工作流程实现对RP标本的术中评估， 对于广泛的临床应用是可行的。我们的假设是：NLM可用于快速评估前列腺 并在不增加切缘阳性率的情况下增加保留神经的RP率。这是一个 与麻省理工学院和贝丝的研究人员合作的多学科项目 以色列女执事医学中心(BIDMC)，哈佛医学院。AIM 1将开发下一代NLM 用于快速、全面评估RP中前列腺标本的技术和临床工作流程。这些 先进技术将使一个两人团队(组织技术/住院医生和病理学家)能够进行全面的NLM 与NeuroSAFE相比，RP边缘与神经血管束相邻，速度更快，人员更少。 AIM 2将对接受机器人RP的患者进行随机对照试验。主端点将 神经保留RPS的比率和神经血管邻近区域手术切缘的阳性比率 接受术中NLM切缘评估和术后护理标准的研究组中的束 FFPE组织学与接受标准护理的FFPE术后组织学对照。第二个 终点将是术中NLM与研究臂和术后组织学之间的一致性 研究组和对照组的手术时间。AIM 3将开发NLM技术和工作流，以实现 远程NLM评估，这将增加接触具有专科专业知识的病理学家的机会，Streamline 病理学家的工作流程，并促进采用术中边缘评估的RP。

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.