Detection of High Grade Prostate Cancer with Subharmonic Ultrasound Imaging

 描述（由申请人提供）：前列腺癌（PCa）是美国男性中最常诊断的癌症，占新发癌症诊断的27%，但仅直接导致9.5%的癌症相关死亡。最近发表的两项临床试验表明，过度诊断和过度治疗可能无关紧要的癌症是前列腺癌筛查的一个主要缺点，并指出需要一种更具体的筛查工具，可以识别临床上显著的前列腺癌。美国的前列腺癌、肺癌、结直肠癌和卵巢癌（PLCO）筛查试验未能显示前列腺癌筛查和治疗的死亡率获益。欧洲前列腺癌筛查随机研究（ERSPC）表明，按照目前的护理标准，必须对1410名男性进行筛查，并额外治疗48例前列腺癌病例，以防止一例前列腺癌死亡。基于这些试验，美国预防服务工作组（USPSTF）已经发布了一个“D”级建议，反对基于PSA的PCa筛查。超声造影：最近的研究表明，对比度增强谐波成像（HI）可以识别与血管血流相关的增强，在较高级别的前列腺癌，HI可以选择性地检测患者的“临床意义”的前列腺癌，最有可能从治疗中受益。次谐波成像（SHI）是一种用于对比增强超声成像的较新技术，可将小血管结构可视化的信号与背景比提高10倍，但以前尚未在经直肠超声探头上实现。前列腺的SHI有望推进前列腺新生血管的成像，并改善临床显著PCa的选择性活检。目的：使SHI适应于适用于前列腺成像和活检的经直肠探头（在本研究的前6个月内）。随后的18个月初步临床研究将招募50名具有临床适应症的参与者 用于前列腺活检，以量化SHI，用于检测临床显著的PCa（定义为：Gleason评分≥ 7，单个核心受累> 50%，或> 25%的活检核心PCa阳性）。方法：每例受试者将接受经直肠超声评价，采用常规灰度和彩色多普勒成像，以及彩色多普勒、HI和SHI方法的对比度增强成像。将记录每种技术的成像结果，但只有SHI结果将用于指导前列腺的靶向活检。根据SHI确定的可疑区域，将从每例受试者中获得最多6个靶向活检芯。靶向活检后，每名受试者还将接受12部分系统活检，包括6个侧向活检芯和6个 内侧定向活检芯。初步研究旨在评估临床上 将通过基于SHI沿着的靶向活检以及内侧定向系统性六分仪活检芯（总计≤ 12个芯）获得的显著癌症。

 DESCRIPTION (provided by applicant): Prostate cancer (PCa) is the most frequently diagnosed cancer among American males, accounting for 27 % of new cancer diagnoses, but it is directly responsible for only 9.5 % of cancer related deaths. Two recently published clinical trials suggest that overdiagnosis and overtreatment of potentially insignificant cancer is a major drawback of prostate cancer screening, and point to the need for a more specific screening tool that can identify clinically significant prostate cancer. The US-based Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial failed to show a mortality benefit from screening and treatment of prostate cancer. The European Randomized Study of Screening for Prostate Cancer (ERSPC) suggests that with the current standard of care, 1410 men must be screened and 48 additional cases of prostate cancer treated to prevent one death from prostate cancer. Based upon these trials, the U.S. Preventive Services Task Force (USPSTF) has issued a grade "D" recommendation against PSA-based screening for PCa. Contrast-Enhanced Ultrasound: Recent studies have demonstrated that contrast-enhanced harmonic imaging (HI) can identify enhancement related to vascular flow in higher grade PCa, and that HI can selectively detect patients with "clinically significant" PCa that are most likely to benefit from therapy. Subharmonic imaging (SHI) is a newer technology for contrast-enhanced ultrasound imaging that provides a 10-fold improvement in the signal to background ratio for visualization of small vascular structures, but has not been previously implemented on a transrectal ultrasound probe. SHI of the prostate is expected to advance the imaging of prostatic neovascularity and to improve selective biopsy of clinically significant PCa. Objective: To adapt SHI to a transrectal probe appropriate for prostate imaging and biopsy (over the first 6 months of this study). The subsequent 18 month pilot clinical study will enroll 50 participants who have a clinical indication for prostate biopsy to quantify SHI for the detection of clinically significant PCa (defined as: Gleason score ≥ 7, a single core with > 50 % involvement, or > 25 % of biopsy cores positive for PCa). Approach: Each participant will undergo a transrectal ultrasound evaluation of the prostate with conventional grayscale and color Doppler imaging, as well as contrast-enhanced imaging with color Doppler, HI and SHI approaches. Imaging results from each of these techniques will be recorded, but only the SHI findings will be used to guide a targeted biopsy of the prostate. A maximum of 6 targeted biopsy cores will be obtained from each participant, based upon suspicious areas identified with SHI. Following the targeted biopsy, each participant will also receive a 12-part systematic biopsy consisting of 6 laterally directed biopsy cores and 6 medially directed biopsy cores. The pilot study is designed to estimate the detection of clinically significant cancer that will be obtained with targeted biopsy based upon SHI along with the medially directed systematic sextant biopsy cores (≤ 12 cores total).