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World J Clin Oncol. May 24, 2022; 13(5): 314-322
Published online May 24, 2022. doi: 10.5306/wjco.v13.i5.314
Neoadjuvant treatment in non-small cell lung cancer: New perspectives with the incorporation of immunotherapy
Carlos Aguado, Luis Chara, Mónica Antoñanzas, Jose Maria Matilla Gonzalez, Unai Jiménez, Raul Hernanz, Xabier Mielgo-Rubio, Juan Carlos Trujillo-Reyes, Felipe Couñago
Carlos Aguado, Mónica Antoñanzas, Department of Medical Oncology, Hospital Clínico Universitario San Carlos, Madrid 28040, Spain
Luis Chara, Department of Medical Oncology, Hospital Universitario de Guadalajara, Guadalajara 19002, Spain
Jose Maria Matilla Gonzalez, Department of Thoracic Surgery, Hospital Clínico Universitario de Valladolid, Valladolid 47005, Spain
Unai Jiménez, Department of Thoracic Surgery, Hospital Universitario Cruces, Barakaldo, Bizkaia 48903, Basque Country, Spain
Raul Hernanz, Department of Radiation Oncology, Hospital Universitario Ramón y Cajal, Madrid 28034, Spain
Xabier Mielgo-Rubio, Department of Medical Oncology, Hospital Universitario Fundación Alcorcón, Alcorcón 28922, Madrid, Spain
Juan Carlos Trujillo-Reyes, Department of Thoracic Surgery, Hospital de la Santa Creu I Sant Pau, Barcelona 08029, Catalonia, Spain
Juan Carlos Trujillo-Reyes, Department of Surgery, Universitat Autonoma de Barcelona, Barcelona 08029, Catalonia, Spain
Felipe Couñago, Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid, Pozuelo de Alarcón 28223, Madrid, Spain
Felipe Couñago, Department of Radiation Oncology, Hospital La Luz, Madrid 28003, Spain
Felipe Couñago, Medicine Department, School of Biomedical Sciences, Universidad Europea de Madrid, Villaviciosa de Odón 28670, Madrid, Spain
Author contributions: Aguado C, Chara LE, Antoñanzas M, Matilla JM, Jiménez U and Hernanz R drafted the manuscript; Couñago F, Trujillo JC and Mielgo-Rubio X critically revised the content of the manuscript.
Conflict-of-interest statement: Authors declare no conflict of interests related to this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Carlos Aguado, MD, Consultant Physician-Scientist, Department of Medical Oncology, Hospital Clínico Universitario San Carlos, Calle del Prof Martín Lagos, s/n, Madrid 28040, Spain. carlos.aguado84@gmail.com
Received: April 28, 2021
Peer-review started: April 28, 2021
First decision: June 7, 2021
Revised: June 24, 2021
Accepted: May 7, 2022
Article in press: May 7, 2022
Published online: May 24, 2022
Processing time: 391 Days and 4.3 Hours
Abstract

The aim of neoadjuvant treatment in non-small cell lung cancer (NSCLC) is to eliminate micrometastatic disease to facilitate surgical resection. Neoadjuvant chemotherapy (ChT) in localised NSCLC has numerous advantages over other therapeutic modalities and is considered standard treatment in resectable disease. Treatment with immune checkpoint inhibitors (ICI) improves long-term survival in advanced disease and has a better toxicity profile than conventional therapies. These immunotherapy agents (anti-PD1/PD-L1), administered with or without ChT, are currently being evaluated in the preoperative setting, with initial results showing better pathological response rates and more long-term benefits. Importantly, these drugs do not appear to increase the rate of severe adverse effects and/or postoperative complications. However, several questions still need to be resolved, including the identification of predictive biomarkers; comparative studies of immunotherapy alone vs combined treatment with ChT and/or radiotherapy; the optimal duration of treatment; the timing of surgery; the need for adjuvant treatment; appropriate radiologic evaluation and mediastinal staging; and the correlation between pathological response and survival outcomes. Here we review the current evidence for immunotherapy from a multidisciplinary perspective and discuss current and future controversies.

Keywords: Non-small cell lung cancer; Neoadjuvant; Immune checkpoint inhibitors; Immunotherapy; Anti-PD1; Anti-PD-L1; Complete pathological response

Core Tip: Studies evaluating neoadjuvant immunotherapy in non-small cell lung cancer have reported extraordinary pathological response rates without any increase in postoperative complications. However, before immunotherapy is implemented in routine clinical practice, several issues still need to be resolved. This review analyses the current evidence for immunotherapy from a multidisciplinary perspective and discusses current and future controversies.