Ma Lina, Sullivan Travis B, Rieger-Christ Kimberly M, Yambayev Ilyas, Zhao Qing, Higgins Sara E, Yilmaz Osman H, Sultan Lila, Servais Elliot L, Suzuki Kei, Burks Eric J
Department of Pathology & Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston Medical Center, Boston, Mass.
Department of Translational Research, Ian C. Summerhayes Cell and Molecular Biology Laboratory, Lahey Hospital & Medical Center, Burlington, Mass.
JTCVS Open. 2023 Nov 13;16:938-947. doi: 10.1016/j.xjon.2023.11.003. eCollection 2023 Dec.
Recent randomized control trials (JCOG0802 and CALGB140503) have shown sublobar resection to be noninferior to lobectomy for non-small cell lung cancer (NSCLC) ≤2.0 cm. We have previously proposed histologic criteria stratifying lung adenocarcinoma into indolent low malignant potential (LMP) and aggressive angioinvasive adenocarcinomas, resulting in better prognostication than provided by World Health Organization grade. Here we determine whether pathologic classification is reproducible and whether subsets of adenocarcinomas predict worse outcomes when treated by wedge resection compared to lobectomy.
A retrospective cohort of 108 recipients of wedge resection and 187 recipients of lobectomy for stage I/0 lung adenocarcinomas ≤2.0 cm was assembled from 2 institutions. All tumors were classified by a single pathologist, and interobserver reproducibility was assessed in a subset (n = 92) by 5 pathologists.
Angioinvasive adenocarcinoma (21%-27% of cases) was associated with worse outcomes when treated with wedge resection compared to lobectomy (5-year recurrence-free survival, 57% vs 85% [ = .007]; 5-year disease-free survival [DSS], 70% vs 90% [ = .043]; 7-year overall survival, 37% vs 58% [ = .143]). Adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and LMP exhibited 100% 5-year DSS regardless of the surgical approach. Multivariable analysis showed that angioinvasion, tumor size, margin status, and extent of nodal sampling were significantly associated with recurrence but not with surgical procedure. There was substantial interobserver reproducibility among the pathologists for the diagnosis of angioinvasive adenocarcinoma (κ = 0.71) and the combined indolent AIS/MIA/LMP group (κ = 0.74).
The majority (∼75%) of lung adenocarcinomas ≤2 cm are adequately managed with wedge resection; however, angioinvasive adenocarcinomas (∼25%) treated by wedge resection with suboptimal nodal sampling exhibit poor outcomes, with a 40% to 45% rate of recurrence within 5 years and 60% to 65% overall mortality at 7 years.
近期的随机对照试验（JCOG0802和CALGB140503）表明，对于直径≤2.0 cm的非小细胞肺癌（NSCLC），亚肺叶切除术并不劣于肺叶切除术。我们之前提出了组织学标准，将肺腺癌分为惰性低恶性潜能（LMP）腺癌和侵袭性血管浸润性腺癌，与世界卫生组织分级相比，该标准能实现更好的预后评估。在此，我们确定病理分类是否具有可重复性，以及与肺叶切除术相比，楔形切除术治疗的腺癌亚组是否预示着更差的预后。
从2家机构收集了108例接受楔形切除术和187例接受肺叶切除术的I/0期肺腺癌患者队列，肿瘤直径均≤2.0 cm。所有肿瘤均由一名病理学家进行分类，并由5名病理学家对一个亚组（n = 92）进行观察者间可重复性评估。
与肺叶切除术相比，侵袭性血管浸润性腺癌（占病例的21%-27%）接受楔形切除术治疗时预后较差（5年无复发生存率，57%对85%[P = 0.007]；5年无病生存率[DSS]，70%对90%[P = 0.043]；7年总生存率，37%对58%[P = 0.143]）。原位腺癌（AIS）、微浸润腺癌（MIA）和LMP腺癌无论采用何种手术方式，5年DSS均为100%。多变量分析显示，血管浸润、肿瘤大小、切缘状态和淋巴结采样范围与复发显著相关，但与手术方式无关。病理学家对侵袭性血管浸润性腺癌的诊断（κ = 0.71）以及惰性AIS/MIA/LMP联合组的诊断（κ = 0.74）具有较高的观察者间可重复性。
大多数（约75%）直径≤2 cm的肺腺癌通过楔形切除术可得到充分治疗；然而，接受楔形切除术且淋巴结采样不理想的侵袭性血管浸润性腺癌（约25%）预后较差，5年内复发率为40%至45%，7年总死亡率为60%至65%。
