Microscopical predictors and Tumor Immune Microenvironment (TIME) have been studied less in early-stage NSCLC due to the curative intent of resection and the satisfactory survival rate achievable. Despite this, the emerging literature enforces the role of the immune system and microscopical predictors as prognostic variables in NSCLC and in adenocarcinomas (ADCs) as well. Here, we investigated whether cancer-related microscopical variables and TIME influence survival and recurrence in I-IIA ADCs. We retrospectively collected I-IIA ADCs treated (lobectomy or segmentectomy) at the University Hospital (Padova) between 2016 and 2022. We assigned to pathological variables a cumulative pathological score (PS) resulting as the sum of them. TIME was investigated as tumor-infiltrating lymphocytes (TILs < 11% or ≥11%) and PD-L1 considering its expression (<1% or ≥1%). Then, we compared survival and recurrence according to PS, histology, TILs and PD-L1. A total of 358 I-IIA ADCs met the inclusion criteria. The median PS grew from IA1 to IIA, indicating an increasing microscopical cancer activity. Except for the T-SUVmax, any pathological predictor seemed to be different between PD-L1 < 1% and ≥1%. Histology, PS, TILs and PD-L1 were unable to indicate a survival difference according to the Log-rank test (p= 0.37,p= 0.25,p= 0.41 andp= 0.23). Even the recurrence was non-significant (p= 0.90,p= 0.62,p= 0.97,p= 0.74). According to our findings, resection remains the best upfront treatment in I-IIA ADCs. Microscopical cancer activity grows from IA1 to IIA tumors, but it does not affect outcomes. These outcomes are also unmodified by TIME. Probably, microscopical cancer development and immune reaction against cancer are overwhelmed by an adequate R0-N0 resection.
由于早期非小细胞肺癌（NSCLC）可通过手术切除达到治愈目的且生存率较为理想，其微观预测因子及肿瘤免疫微环境（TIME）的相关研究相对较少。尽管如此，新近文献不断强调免疫系统及微观预测因子在NSCLC（包括肺腺癌）预后评估中的重要作用。本研究旨在探讨癌症相关微观变量与TIME是否影响I-IIA期肺腺癌患者的生存及复发情况。我们回顾性收集了2016年至2022年间在帕多瓦大学医院接受肺叶或肺段切除术的I-IIA期肺腺癌病例，通过整合病理变量构建累积病理评分（PS），并基于肿瘤浸润淋巴细胞（TILs＜11%或≥11%）及PD-L1表达水平（＜1%或≥1%）评估TIME特征。随后根据PS、组织学类型、TILs及PD-L1表达进行生存与复发比较分析。 研究共纳入358例符合标准的I-IIA期肺腺癌。结果显示，从IA1期到IIA期，中位PS呈递增趋势，提示微观肿瘤活性随分期进展而增强。除T-SUVmax外，其他病理预测因子在PD-L1不同表达组间未见显著差异。对数秩检验显示组织学类型、PS、TILs及PD-L1均未提示生存差异（p值分别为0.37、0.25、0.41、0.23），复发风险亦无统计学意义（p值分别为0.90、0.62、0.97、0.74）。本研究结果表明，手术切除仍是I-IIA期肺腺癌的最佳首选治疗方案。虽然微观肿瘤活性随分期进展而增强，但并未影响临床结局，TIME特征亦未改变预后表现。这可能是因为充分的R0切除及淋巴结阴性状态（N0）已完全控制了微观肿瘤进展及机体抗肿瘤免疫反应的影响。
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