Conversion to Thoracotomy After Neoadjuvant Immune Checkpoint Inhibitor Therapy for Resectable Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Predictors, Technical Complexity, and Perioperative Outcomes
Downloads
Neoadjuvant chemoimmunotherapy has become an established treatment option for selected patients with resectable non-small cell lung cancer (NSCLC), although treatment-associated hilar fibrosis may increase surgical complexity. Conversion from minimally invasive surgery to open thoracotomy is an important indicator of technical difficulty; however, it has generally been reported as a secondary outcome and has not been comprehensively synthesized as a primary endpoint. This systematic review and meta-analysis aimed to estimate the incidence of conversion to thoracotomy following neoadjuvant immune checkpoint inhibitor (ICI)-based therapy and identify factors contributing to variability across studies. PubMed, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from database inception through September 19, 2026. Two independent reviewers screened studies, extracted data, and assessed methodological quality, resolving disagreements through discussion. Full-text articles were reviewed to determine eligibility. Studies were included if they enrolled adults with resectable NSCLC who received neoadjuvant ICI-based therapy, underwent an attempted minimally invasive pulmonary resection, and reported sufficient data to determine conversion events and the corresponding denominator. Conversion proportions were pooled using the Freeman–Tukey double-arcsine transformation and a DerSimonian–Laird random-effects model. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Twenty studies comprising 1,221 attempted minimally invasive resections reported 164 conversions to thoracotomy. The pooled conversion rate was 12.2% (95% confidence interval [CI]: 9.0%–15.8%), with moderate between-study heterogeneity (I² = 51.7%) and a 95% prediction interval of 3.2%–24.9%. Surgical approach was associated with significant variation in conversion rates, which were 1.9% in robotic-assisted thoracic surgery (RATS) series, 12.4% in video-assisted thoracoscopic surgery (VATS) series, and 14.6% in series involving mixed surgical approaches (p = 0.006). Overall, approximately one in eight attempted minimally invasive pulmonary resections following neoadjuvant ICI-based therapy required conversion to open thoracotomy. Surgical approach was associated with differences in conversion rates across studies, whereas geographic location and cohort size were not identified as significant sources of variation.
Aburaki, R., Fujiwara, Y., Chida, K., Horita, N., & Nagasaka, M. (2024). Surgical and safety outcomes in patients with non-small cell lung cancer receiving neoadjuvant chemoimmunotherapy versus chemotherapy alone: A systematic review and meta-analysis. Cancer Treatment Reviews, 131, 102833. https://doi.org/10.1016/j.ctrv.2024.102833
Bendixen, M., OD, J., Kronborg, C., Andersen, C., & PB, L. (2016). Postoperative pain and quality of life after lobectomy via video-assisted thoracoscopic surgery or anterolateral thoracotomy for early stage lung cancer: a randomised controlled trial. Lancet Oncol, 17(6), 836–844. https://doi.org/10.1016/S1470-2045(16)00173-X
Bray, F., Laversanne, M., Sung, H., Ferlay, J., RL, S., & Soerjomataram I. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 74(3), 229–263. https://doi.org/10.3322/caac.21834
Cascone, T., MM, A., JD, S., He, J., Lu, S., & Sepesi B. (2024). Perioperative Nivolumab in Resectable Lung Cancer. N Engl J Med, 390(19), 1756–1769. https://doi.org/10.1056/NEJMoa2311926
Chu, N.-Q., Tan, K. S., Dycoco, J., Adusumilli, P. S., Bains, M. S., & Bott, M. J. (2025). Determinants of successful minimally invasive surgery for resectable non-small cell lung cancer after neoadjuvant therapy. The Journal of Thoracic and Cardiovascular Surgery, 169(3), 753-762.e6. https://doi.org/10.1016/j.jtcvs.2024.08.012
JV, H., Harpole, D., Mitsudomi, T., JM, T., Galffy, G., & Hochmair M. (2023). Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N Engl J Med, 389(18), 1672–1684. https://doi.org/10.1056/NEJMoa2304875
Li, H.-J., Ding, J.-Y., Nie, Q., Hong, H.-Z., Qiu, Z.-B., & Fu, R. (2025). Advantages of robotic-assisted thoracic surgery after neoadjuvant therapy in NSCLC: A propensity score-matched analysis. European Journal of Surgical Oncology, 51(8), 110022. https://doi.org/10.1016/j.ejso.2025.110022
Lim, E., RA, H., HE, M., TJ, B., Dunning, J., & Shackcloth M. (2022). Impact of video-assisted thoracoscopic lobectomy versus open lobectomy for lung cancer on recovery assessed using self-reported physical function: VIOLET RCT. Health Technol Assess, 26(48), 1–162. https://doi.org/10.3310/THBQ1793
Pan, H., Chen, H., Kong, W., Ge, Z., Zhang, J., & Tian, Y. (2025). Minimally invasive surgery could be attempted with preoperatively predictable difficulty for non-small cell lung cancer after neoadjuvant immunochemotherapy: A large multicenter study. Surgery, 184, 109458. https://doi.org/10.1016/j.surg.2025.109458
PM, F., JD, S., Provencio, M., Mitsudomi, T., MM, A., & Wang C. (2025). Overall Survival with Neoadjuvant Nivolumab plus Chemotherapy in Lung Cancer. N Engl J Med, 393(8), 741–752. https://doi.org/10.1056/NEJMoa2502931
PM, F., Spicer, J., Lu, S., Provencio, M., Mitsudomi, T., & Awad MM. (2022). Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med, 386(21), 1973–1985. https://doi.org/10.1056/NEJMoa2202170
Pohlman, A., Marten, A. D., Coughlin, J. M., Lubawski, J., Raad, W., & Abdelsattar, Z. M. (2026). Impact of Neoadjuvant Therapy, Tumor Size, and Surgical Approach on Conversion to Open Thoracotomy During Lobectomy. The Annals of Thoracic Surgery, 122(4), 948–956. https://doi.org/10.1016/j.athoracsur.2026.03.046
Provencio, M., Nadal, E., JL, G.-L., Martínez-Martí, A., Bernabé, R., & Bosch-Barrera J. (2023). Perioperative Nivolumab and Chemotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med, 389(6), 504–513. https://doi.org/10.1056/NEJMoa2215530
Shah, S. K., Khan, A. A., Basu, S., & Seder, C. W. (2025). Minimally Invasive Pneumonectomy vs Open Pneumonectomy: Outcomes and Predictors of Conversion. The Annals of Thoracic Surgery, 119(3), 634–642. https://doi.org/10.1016/j.athoracsur.2024.07.027
Spicer, J. D. (2024). Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab compared with neoadjuvant chemotherapy alone in patients with early-stage non-small-cell lung cancer (KEYNOTE-671): a randomised, double-blind, placebo-controlled, phase 3 tria. The Lancet, 404(10459), 1240–1252. https://doi.org/10.1016/S0140-6736(24)01756-2
Tajè, R., Gallina, F. T., & Spicer, J. D. (2026). Stage II Non-Small Cell Lung Cancer: Upfront Surgery or Neoadjuvant Chemoimmunotherapy. The Annals of Thoracic Surgery. https://doi.org/10.1016/j.athoracsur.2026.05.037
Wakelee, H., Liberman, M., Kato, T., Tsuboi, M., SH, L., & Gao S. (2023). Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J Med, 389(6), 491–503. https://doi.org/10.1056/NEJMoa2302983
Wang, M. (2025). Conversion surgery for initially unresectable stage III non-small cell lung cancer after induction treatment of immunochemotherapy: A multicenter study. Clinical Lung Cancer, 26, e131-e140.e1. https://doi.org/10.1016/j.cllc.2024.11.005
WD, T., Dacic, S., Wistuba, I., Sholl, L., Adusumilli, P., & Bubendorf L. (2020). IASLC Multidisciplinary Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy. J Thorac Oncol, 15(5), 709–740. https://doi.org/10.1016/j.jtho.2020.01.005
Yang, Z., Wang, S., Yang, H., Jiang, Y., & Zhu, L. (2024). Treatment patterns and clinical outcomes of patients with resectable non-small cell lung cancer receiving neoadjuvant immunochemotherapy: A large-scale, multicenter, real-world study (NeoR-World). The Journal of Thoracic and Cardiovascular Surgery, 168(4), 1245-1258.e17. https://doi.org/10.1016/j.jtcvs.2024.02.006
Copyright (c) 2026 Stevano Mengko, Pedro Sutrisno, Elia Afry Parlindungan Hutapea
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-ShareAlike 4.0 International (CC-BY-SA). that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
