新辅助免疫联合化疗（NICT）已成为可切除的非小细胞肺癌（NSCLC）的标准治疗模式，但约80%的患者术后仍存在残留病灶（非病理完全缓解，non-pCR）。这部分患者的长期生存显著低于达到病理完全缓解（pCR）的患者，5 年总生存（OS）率约55%，成为当前围手术期治疗的重大挑战。借鉴乳腺癌领域对non-pCR患者实施辅助强化治疗（如恩美曲妥珠单抗、卡培他滨）的经验，本文探讨NSCLC在NICT后non-pCR人群的辅助治疗策略优化路径。重点分析了多种具有潜力的辅助强化手段，包括抗血管生成药物、抗体药物偶联物（ADC）、双特异性抗体（BsAb）、个体化新抗原疫苗及放疗和口服化疗药物等，旨在为清除耐药残留克隆提供新策略。同时提出可根据残留存活肿瘤（RVT）比例对复发风险进行精细分层、基于分子残留病灶（MRD）进行动态监测，建立整合RVT与MRD状态的风险自适应模型，以实现“因人施策”的个体化辅助强化治疗，以期改善non-pCR NSCLC人群的生存预后，并为该领域提供理论依据与研究方向。

Neoadjuvant immunotherapy combined with chemotherapy (NICT) has become a standard treatment modality for patients with resectable non-small cell lung cancer (NSCLC). However, approximately 80% of patients still have residual disease (non- pathological complete response, non-pCR) after surgery. These patients exhibit significantly poorer long-term survival compared with those achieving pCR, with a 5-year overall survival rate of approximately 55%, representing a major challenge in current perioperative therapy. Drawing on the successful experience of implementing adjuvant intensification strategies (e.g., ado-trastuzumab emtansine and capecitabine) for non-pCR patients in breast cancer, this article explores the optimization of adjuvant treatment strategies for the non- pCR population following NICT in NSCLC. We focus on analyzing various promising adjuvant intensification approaches, including anti-angiogenic agents, antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), personalized neoantigen vaccines, radiotherapy, and oral chemotherapy agents, aiming to eradicate drug-resistant residual tumor clones. Furthermore, we propose that fine- grained risk stratification based on the residual viable tumor (RVT) proportion and dynamic monitoring of molecular residual disease (MRD) should be implemented. Establishing a risk-adaptive model integrating RVT and MRD status holds promise for achieving an individualized adjuvant intensification strategy, with the goal of improving survival outcomes for non-pCR NSCLC patients. This review provides a theoretical basis and future research directions for adjuvant intensification in patients with non-pCR NSCLC.

国家自然科学基金（82274607）；天津市卫健委中医药重点领域科研项目（2024013）；卫生健康科技发展促进项目—肺癌诊疗研究项目（PMY202410110097-041）