诊断时的循环肿瘤 DNA (ctDNA) 阳性与包括 I-III 期非小细胞肺癌 (NSCLC) 在内的多种实体瘤的较差结果相关，可能有助于指导（新）辅助治疗。 在这项回顾性研究中260 名临床 I 期 NSCLC 患者（180 名腺癌，80 名鳞状细胞癌）根据术后≤5 年的复发与无病状态被分配（2:1）高风险组和低风险组。我们通过仅血浆靶向甲基化的多癌早期检测 (MCED) 测试评估了术前 ctDNA 检测与总体人群术后 ≤5 年 NSCLC 复发的关联，随后进行了组织学特异性亚组分析。对于 I 期患者，术前 ctDNA 检测与术后 5 年内复发无关。仅限于肺腺癌的子分析表明 ctDNA 检测与结果之间存在组织学特异性关联。在该组中，ctDNA 阳性往往与 2 年内复发相关，这表明 MCED 测试阳性的预后影响可能与 I 期 NSCLC 的组织学和时间相关。术前 ctDNA 检测与临床 I 期升级为病理 II-III 期 NSCLC 相关。我们的研究结果表明，使用 MCED（一种专为无症状人群开发的泛癌筛查测试）对可切除的临床 I 期 NSCLC 患者进行术前 ctDNA 检测，对于术后≤5年的复发没有可检测的预后价值。 MCED 检测可能与早期腺癌复发和 I 期 NSCLC 病理分期率增加有关。然而，鉴于这些发现的探索性，需要进行独立验证。版权所有 © 2024。由 Elsevier B.V. 出版。

Circulating tumor DNA (ctDNA) positivity at diagnosis, which is associated with worse outcomes in multiple solid tumors including stage I-III non-small cell lung cancer (NSCLC), may have utility to guide (neo)adjuvant therapy.In this retrospective study, 260 patients with clinical stage I NSCLC (180 adenocarcinoma, 80 squamous cell carcinoma) were allocated (2:1) to high- and low-risk groups based on relapse versus disease-free status ≤5 years post-surgery. We evaluated the association of preoperative ctDNA detection by a plasma-only targeted methylation-based multi-cancer early detection (MCED) test with NSCLC relapse ≤5 years post-surgery in the overall population, followed by histology-specific subgroup analyses.Across clinical stage I patients, preoperative ctDNA detection did not associate with relapse within 5 years post-surgery. Sub-analyses confined to lung adenocarcinoma suggested a histology-specific association between ctDNA detection and outcome. In this group, ctDNA positivity tended to associate with relapse within 2 years, suggesting prognostic implications of MCED test positivity may be histology- and time-dependent in stage I NSCLC. Preoperative ctDNA detection was associated with upstaging of clinical stage I to pathological stage II-III NSCLC.Our findings suggest preoperative ctDNA detection in patients with resectable clinical stage I NSCLC using MCED, a pan-cancer screening test developed for use in an asymptomatic population, has no detectable prognostic value for relapse ≤5 years post-surgery. MCED detection may be associated with early adenocarcinoma relapse and increased pathological upstaging rates in stage I NSCLC. However, given the exploratory nature of these findings, independent validation is required.Copyright © 2024. Published by Elsevier B.V.