Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan.
Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan.
JAMA Netw Open. 2021 Sep 1;4(9):e2125317. doi: 10.1001/jamanetworkopen.2021.25317.
Distinguishing between mucosal and submucosal cancers is important for selecting the optimal treatment for patients with esophageal squamous cell carcinoma (ESCC); however, standard procedures for diagnosing cancer invasion depth have not yet been determined.
To evaluate the diagnostic performance of endoscopic ultrasonography (EUS) after conventional endoscopy for the evaluation of ESCC invasion depth.
DESIGN, SETTING, AND PARTICIPANTS: This prospective single-arm confirmatory diagnostic study comprising 372 patients with T1 esophageal cancer was conducted at 41 secondary or tertiary hospitals in Japan. Enrollment began on July 20, 2017; patients were enrolled in 2 steps, with the first registration occurring from August 4, 2017, to December 11, 2019, and the second from August 9, 2017, to December 11, 2019. After the completion of all first and second registration examinations, patients received treatment and were followed up for 30 days, with follow-up ending on February 14, 2020. Patients were eligible for inclusion if they had pathologically or endoscopically diagnosed esophageal cancer with T1 clinical depth of invasion.
In the first registration, nonmagnifying endoscopy (non-ME) and magnifying endoscopy (ME) were used to diagnose cancer invasion depth. In the second registration, patients from the first registration who had cancers invading the muscularis mucosa or submucosa were enrolled and received EUS. After completion of the protocol examinations, patients received treatment with endoscopic resection or esophagectomy. The pathological results of the resected specimens were used as the reference standard for evaluating cancer invasion depth.
The primary end point was the proportion of overdiagnosis of submucosal cancer (defined as invasion depth >200 μm) after receipt of non-ME and ME, with or without the addition of EUS. The secondary end points were underdiagnosis, sensitivity, and specificity.
Among 372 patients enrolled in the first registration, 371 received non-ME and ME. Of those, 300 patients were enrolled in the second registration, and 293 patients received EUS. A total of 269 patients (217 men [80.7%]; median age, 69 years; interquartile range, 62-75 years) were included in the final analysis. The addition of EUS was associated with a 6.6% increase in the proportion of overdiagnosis (from 16 of 74 patients [21.6%; 95% CI, 12.9%-32.7%] after non-ME and ME to 29 of 103 patients [28.2%; 95% CI, 19.7%-37.9%] after the addition of EUS; 1-sided P = .93). All subgroup analyses found similar increases in overdiagnosis of submucosal cancer. The addition of EUS was associated with a 4.5% reduction in the proportion of underdiagnosis (from 57 of 195 patients [29.2%; 95% CI, 23.0%-36.2%] after non-ME and ME to 41 of 166 patients [24.7%; 95% CI, 18.3%-32.0%] after the addition of EUS). After non-ME and ME, diagnostic sensitivity was 50.4% (95% CI, 41.0%-59.9%), specificity was 89.6% (95% CI, 83.7%-93.9%), and accuracy was 72.9% (95% CI, 67.1%-78.1%). After the addition of EUS, diagnostic sensitivity was 64.3% (95% CI, 54.9%-73.1%), specificity was 81.2% (95% CI, 74.1%-87.0%), and accuracy was 74.0% (95% CI, 68.3%-79.1%).
This study found that the addition of EUS was not associated with improvements in the diagnostic accuracy of cancer invasion depth. These findings do not support the routine use of EUS after conventional endoscopy for evaluating the invasion depth among patients with T1 ESCC.
区分黏膜内癌和黏膜下癌对于选择食管鳞状细胞癌(ESCC)患者的最佳治疗方法很重要;然而,对于癌症浸润深度的诊断标准程序尚未确定。
评估内镜超声检查(EUS)在常规内镜检查后对 ESCC 浸润深度评估的诊断性能。
设计、设置和参与者:这项前瞻性单臂确证性诊断研究纳入了日本 41 家二级或三级医院的 372 例 T1 食管癌患者。招募于 2017 年 7 月 20 日开始,第一阶段登记于 2017 年 8 月 4 日至 2019 年 12 月 11 日进行,第二阶段登记于 2017 年 8 月 9 日至 2019 年 12 月 11 日进行。所有第一阶段和第二阶段登记检查完成后,患者接受治疗并随访 30 天,随访于 2020 年 2 月 14 日结束。如果患者有经病理或内镜诊断为 T1 临床浸润深度的食管癌,则符合纳入标准。
在第一阶段登记中,使用非放大内镜(非-ME)和放大内镜(ME)诊断癌症浸润深度。在第二阶段登记中,从第一阶段登记中招募了那些癌症侵犯黏膜肌层或黏膜下层的患者,并接受了 EUS。在完成协议检查后,患者接受内镜下切除或食管切除术治疗。切除标本的病理结果被用作评估癌症浸润深度的参考标准。
主要终点是在接受非-ME 和 ME 后,以及在添加 EUS 后,黏膜下癌(定义为浸润深度>200 μm)的过度诊断比例。次要终点是低估、敏感性和特异性。
在 372 名纳入第一阶段登记的患者中,371 名患者接受了非-ME 和 ME。其中,300 名患者纳入第二阶段登记,293 名患者接受了 EUS。共有 269 名患者(217 名男性[80.7%];中位年龄 69 岁;四分位距 62-75 岁)纳入最终分析。与添加 EUS 相比,黏膜下癌过度诊断的比例增加了 6.6%(从非-ME 和 ME 后 74 例患者中的 16 例[21.6%;95%CI,12.9%-32.7%]增加到添加 EUS 后 103 例患者中的 29 例[28.2%;95%CI,19.7%-37.9%];单侧 P=0.93)。所有亚组分析均发现黏膜下癌过度诊断的比例相似增加。与添加 EUS 相比,黏膜下癌的低估比例降低了 4.5%(从非-ME 和 ME 后 195 例患者中的 57 例[29.2%;95%CI,23.0%-36.2%]降低到添加 EUS 后 166 例患者中的 41 例[24.7%;95%CI,18.3%-32.0%])。在非-ME 和 ME 后,诊断敏感性为 50.4%(95%CI,41.0%-59.9%),特异性为 89.6%(95%CI,83.7%-93.9%),准确性为 72.9%(95%CI,67.1%-78.1%)。在添加 EUS 后,诊断敏感性为 64.3%(95%CI,54.9%-73.1%),特异性为 81.2%(95%CI,74.1%-87.0%),准确性为 74.0%(95%CI,68.3%-79.1%)。
本研究发现,添加 EUS 并未改善癌症浸润深度的诊断准确性。这些发现不支持在常规内镜检查后常规使用 EUS 来评估 T1 ESCC 患者的浸润深度。