Expert Consensus on Perioperative Immunotherapy for Local Advanced Non-Small Cell Lung Cancer

Bin Qiu; Kaican Cai; Chun Chen; Jun Chen; Ke-Neng Chen; Qi-Xun Chen; Chao Cheng; Tian-Yang Dai; Junqiang Fan; Zhaohui Fan; Jian Hu; Wei-Dong Hu; Yun-Chao Huang; Ge-Ning Jiang; Jie Jiang; Tao Jiang; Wen-Jie Jiao; He-Cheng Li; Qiang Li; Yong-De Liao; Hong-Xu Liu; Jun-Feng Liu; Lunxu Liu; Yang Liu; Hao Long; Qing-Quan Luo; Hai-Tao Ma; Nai-Quan Mao; Xiao-Jie Pan; Fengwei Tan; Li-Jie Tan; Hui Tian; Dong Wang; Wen-Xiang Wang; Li Wei; Nan Wu; Qing-Chen Wu; Jiaqing Xiang; Shi-Dong Xu; Lin Yang; Hao Zhang; Lanjun Zhang; Peng Zhang; Yi Zhang; Zhenfa Zhang; Kunshou Zhu; Yuming Zhu; Sang-Won Um; In-Jae Oh; Yusuke Tomita; Satoshi Watanabe; Takeo Nakada; Nobuhiko Seki; Toyoaki Hida; Shinji Sasada; Junji Uchino; Haruhiko Sugimura; Said Dermime; Federico Cappuzzo; Stefania Rizzo; William Chi-Shing Cho; Pierfilippo Crucitti; Filippo Longo; Kye Young Lee; Dirk De Ruysscher; Ben G. L. Vanneste; Muhammad Furqan; Jessica C. Sieren; Sai Yendamuri; Kenneth W. Merrell; Julian R. Molina; Giulio Metro; Raffaele Califano; Stefano Bongiolatti; Mariano Provencio; Paul Hofman; Shugeng Gao; Jie He


Transl Lung Cancer Res. 2021;10(9):3713-3736. 

In This Article


The treatment of lung cancer is one of the major challenges in the field of oncology. According to statistics from the National Cancer Center of China in 2015, lung cancer has the highest incidence and mortality, with 733,300 new cases and 610,200 deaths across the country.[1] About 85% of lung cancers are non-small cell lung cancer (NSCLC), of which 30% to 40% are considered resectable tumors, including most stage I–II and a small portion of stage IIIA tumors.[2]

Very early-stage NSCLC (IA) can be cured by surgery. However, more than 50% of NSCLC patients who undergo surgical treatment will relapse or metastasize within 5 years. Even if there is no lymph node metastasis and the primary tumor is less than 1 cm, nearly 8% of patients still die of the disease within 5 years after anatomical resection.[3,4] To improve the prognosis of resectable NSCLC, adjuvant and neoadjuvant chemotherapy has been widely used as the perioperative treatment. Neoadjuvant chemotherapy can increase the chance of radical resection by reducing tumor volume, eliminating micrometastasis, and reducing tumor recurrence risk. However, the 5-year survival rate of patients receiving either neoadjuvant or adjuvant chemotherapy only improves by approximately 5%.[5,6] The use of the neoadjuvant approach is not common except in the setting of resectable stage IIIA NSCLC and does not yield particularly different survival outcomes. Compared to the adjuvant approach, neoadjuvant therapy can help eliminate micrometastases early on; however, concern for the progression of disease while neoadjuvant therapy is ongoing has inclined the surgical oncology community to operate on tumors early on and rely on systemic therapy in the adjuvant setting.

After the emergence of immune checkpoint inhibitors (ICIs) [programmed cell death protein 1/programmed cell death-ligand 1 (PD-1/L1) antibody and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody], the treatment model for advanced NSCLC has completely changed, and the progression-free survival (PFS) and the overall survival (OS) of patients have been significantly improved. Immunotherapy has moved from the second-line treatment of advanced NSCLC to the first line, and to the consolidation therapy of locally advanced NSCLC patients who receive chemoradiation. Its application has now expanded into the neoadjuvant and adjuvant setting for resectable NSCLC. Immunotherapy use in the neoadjuvant setting is critical because, if the outcome of neoadjuvant therapy improves, then resection of NSCLC can offer cure to a higher number of patients. ICIs have already been shown to provide patients with better survival benefits in the neoadjuvant treatment of melanoma and glioma.[7,8] In some phase II clinical trials of resectable NSCLC, the major pathological response (MPR) rate of patients receiving neoadjuvant immunotherapy was as high as 45%.[9]

In order to reduce clinical staging, increase surgical resection rate, reduce tumor burden, decrease postoperative recurrence, prolong survival, and ultimately achieve the goal of benefiting more patients, a series of clinical trials of perioperative immunotherapy was conducted in recent years. To better guide Chinese thoracic surgeons in the neoadjuvant immunotherapy of NSCLC, the "Expert consensus on neoadjuvant immunotherapy for non-small cell lung cancer" was published last year.[10] However, more recent investigations have employed different strategies of perioperative immunotherapy. To update the current evidence and standardize clinical practice, well-known thoracic surgeons in China participated in an in-depth discussion on controversial issues and topics du jour, forming the 2021 "Expert consensus on perioperative immunotherapy for NSCLC".