Prostate Cancer Diagnosis by Multiparametric Ultrasound

前列腺癌（PCa）是美国男性中最常见的癌症，占美国男性的20%。 PCa是新的癌症诊断，但PCa仅直接导致9%的癌症相关死亡。PSA筛查 有助于PCa的检测，但通过PSA筛查检测到的许多癌症是低至中等的 等级，导致非侵袭性PCa的过度治疗。最近的研究表明，迫切需要有选择地 识别“临床上显著的”PCa，这将导致PCa的成本效益治疗。在过去的几年里， 多参数MRI（mp-MRI）已经成为诊断侵袭性PCa的标准护理。虽然MP- MRI引导活检可以选择性地检测到更高级别的PCa病变，最近的几项研究承认， mp-MRI遗漏了相当多的临床重要病变。此外，由于成本高， MRI，MRI系统可用性的地理差异，用于注册和融合的不精确方法 MRI与超声活检，钆的危险性，在肾功能不全的患者，有一个 需要一种更具成本效益的替代品来检测高等级PCa。最近的研究表明， 对比增强超声（CEUS）可以选择性地检测具有“临床显著”PCa的患者。新 已经提出了增强PCa的常规超声检测的方法，包括分谐波检测， 成像（SHI）、对比增强超声弥散成像（CUDI）和粘弹性成像。客观 该项目的目的是开发一种能够多参数组合超声技术的系统（MP- US）用于检测“临床显著的”PCa。我们将比较3D mp-US和mp-MRI， PCa（定义为：Gleason评分≥ 7，单个核心受累> 50%，或> 25%的活检核心阳性， PCa或Gleason分级组≥ 2，PSA > 10或临床分期cT 2b或更差）。研究的第一年将 致力于在市售3D经直肠探头上实施我们的mp-US技术，以及 涉及使基于MRI的融合/配准系统适应于mp-US。在第二年，我们将优化mp-US 使用机器学习方法，基于与50名根治性直肠癌切除术患者的病理相关性。 研究的最后3年将用于临床试验，其中有300名疑似患有PCa的参与者。 每位参与者将接受一次实验性干预，对最多3个可疑区域进行活检 通过mp-US对前列腺进行经直肠超声评估来识别。为了比较，最多3个 还将基于mp-MRI（临床干预）从每名参与者获得靶向活检芯。 靶向活检后，每例受试者还将接受系统活检（标准治疗），包括 6个侧向活检芯和6个中间活检芯。这项研究证明了 基于mp-US的靶向活检不劣于基于mp-MRI的靶向活检。

Prostate cancer (PCa) is the most frequently diagnosed cancer among American males, accounting for 20% of new cancer diagnoses, but PCa is directly responsible for only 9% of cancer related deaths. PSA screening facilitates the detection of PCa, but many of the cancers detected by PSA screening are low to intermediate grade, resulting in overtreatment of non-aggressive PCa. Recent studies suggest an urgent need to selectively identify “clinically significant” PCa that will result in cost-effective treatment of PCa. In the past few years, multiparametric MRI (mp-MRI) has become the standard of care for diagnosis of aggressive PCa. Although mp- MRI guided biopsy can selectively detect higher grade PCa lesions, several recent studies acknowledge that a considerable number of clinically important lesions are missed by mp-MRI. Furthermore, given the high cost of MRI, the geographic variability in the availability of MRI systems, the inexact methods used to register and fuse MRI with ultrasound for biopsy, and the dangers of Gadolinium in patients with renal insufficiency, there is a need for a more cost-effective, alternative to detect high-grade PCa. Recent studies have demonstrated that contrast-enhanced ultrasound (CEUS) can selectively detect patients with “clinically significant” PCa. New methods have been proposed to enhance conventional ultrasound detection of PCa, including subharmonic imaging (SHI), contrast-enhanced ultrasound dispersion imaging (CUDI) and viscoelastography. The objective of this project is to develop a system capable of a multiparametric combination of ultrasound techniques (mp- US) for detection of “clinically significant” PCa. We will compare 3D mp-US and mp-MRI to identify significant PCa (defined as: Gleason score ≥ 7, a single core with > 50% involvement, or > 25% of biopsy cores positive for PCa or as Gleason grade group ≥ 2, PSA > 10 or clinical stage of cT2b or worse). The first year of the study will be dedicated to implementation of our mp-US technique on a commercially available 3D transrectal probe, and to adapting a MRI-based fusion/registration system to mp-US. During the second year, we will optimize mp-US with a machine learning approach, based upon pathologic correlation with 50 radical prostatectomy patients. The final 3 years of the study will be dedicated to a clinical trial with 300 participants suspected of having PCa. Each participant will receive an experimental intervention in the form of biopsy of up to 3 suspicious areas identified by transrectal ultrasound evaluation of the prostate with mp-US. For comparison, a maximum of 3 targeted biopsy cores will also be obtained from each participant, based on mp-MRI (the clinical intervention). Following the targeted biopsy, each participant will also receive a systematic biopsy (standard of care) consisting of 6 laterally directed biopsy cores and 6 medially directed biopsy cores. The study is powered to demonstrate that targeted biopsy based upon mp-US is not inferior to targeted biopsy based upon mp-MRI.