Thoracic Surgery Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA.
J Clin Oncol. 2011 Nov 10;29(32):4313-9. doi: 10.1200/JCO.2011.35.2500. Epub 2011 Oct 11.
The survival of patients with non-small-cell lung cancer (NSCLC), even when resectable, remains poor. Several small studies suggest that occult metastases (OMs) in pleura, bone marrow (BM), or lymph nodes (LNs) are present in early-stage NSCLC and are associated with a poor outcome. We investigated the prevalence of OMs in resectable NSCLC and their relationship with survival.
Eligible patients had previously untreated, potentially resectable NSCLC. Saline lavage of the pleural space, performed before and after pulmonary resection, was examined cytologically. Rib BM and all histologically negative LNs (N0) were examined for OM, diagnosed by cytokeratin immunohistochemistry (IHC). Survival probabilities were estimated using the Kaplan-Meier method. The log-rank test and Cox proportional hazards regression model were used to compare survival of groups of patients. P < .05 was considered significant.
From July 1999 to March 2004, 1,047 eligible patients (538 men and 509 women; median age, 67.2 years) were entered onto the study, of whom 50% had adenocarcinoma and 66% had stage I NSCLC. Pleural lavage was cytologically positive in only 29 patients. OMs were identified in 66 (8.0%) of 821 BM specimens and 130 (22.4%) of 580 LN specimens. In univariate and multivariable analyses OMs in LN but not BM were associated with significantly worse disease-free survival (hazard ratio [HR], 1.50; P = .031) and overall survival (HR, 1.58; P = .009).
In early-stage NSCLC, LN OMs detected by IHC identify patients with a worse prognosis. Future clinical trials should test the role of IHC in identifying patients for adjuvant therapy.
即使可切除，非小细胞肺癌（NSCLC）患者的生存率仍然很差。几项小型研究表明，早期 NSCLC 存在胸膜、骨髓（BM）或淋巴结（LN）中的隐匿性转移（OMs），并且与不良预后相关。我们研究了可切除 NSCLC 中 OM 的发生率及其与生存率的关系。
符合条件的患者患有未经治疗的、有潜在可切除的 NSCLC。在肺切除术前和术后对胸膜腔进行盐水灌洗，细胞学检查。对所有组织学阴性的 LN（N0）和 Rib BM 进行 OM 检查，通过细胞角蛋白免疫组化（IHC）诊断 OM。使用 Kaplan-Meier 方法估计生存概率。使用对数秩检验和 Cox 比例风险回归模型比较患者组的生存情况。P <.05 被认为具有统计学意义。
1999 年 7 月至 2004 年 3 月，共有 1047 名符合条件的患者（538 名男性和 509 名女性；中位年龄 67.2 岁）入组研究，其中 50%为腺癌，66%为 I 期 NSCLC。仅 29 名患者的胸膜灌洗液细胞学阳性。在 821 份 BM 标本和 580 份 LN 标本中，发现 66 例（8.0%）和 130 例（22.4%）存在 OM。在单变量和多变量分析中，LN 中的 OM 但不是 BM 与疾病无进展生存（HR，1.50；P =.031）和总生存（HR，1.58；P =.009）显著相关更差。
在早期 NSCLC 中，通过 IHC 检测到的 LN OM 可识别预后较差的患者。未来的临床试验应检验 IHC 在识别接受辅助治疗的患者中的作用。
