{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:09:59Z","timestamp":1788775799183,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: In recent years, neoadjuvant chemoimmunotherapy followed by surgery has improved outcomes in patients with stage II\/III non-small cell lung cancer (NSCLC). However, the prognostic impact of residual mediastinal nodal disease after chemoimmunotherapy remains insufficiently defined, particularly with the introduction of the Union for International Cancer Control\/American Joint Committee on Cancer (UICC\/AJCC) 9th edition nodal subclassification. Methods: In this retrospective study, 90 consecutive patients with clinically node-positive (cN1-2) resectable locally advanced NSCLC who underwent neoadjuvant chemoimmunotherapy followed by curative-intent resection were included. Disease-free survival (DFS) was analyzed according to postoperative pathologic nodal status. Nodal status was assessed using the UICC\/AJCC 8th edition (ypN0, ypN1, ypN2) and reclassified according to the 9th edition (ypN0, ypN1, ypN2a, ypN2b). Residual postoperative nodal disease was defined as residual pathologic nodal involvement (ypN+) in patients with clinically node-positive (cN+) disease at baseline. Results: The cohort comprised 90 patients (60% male, median age 63 years [interquartile range (IQR) 58\u201369]). Following neoadjuvant therapy, surgery revealed pathologic nodal clearance in 53 (58.9%) and residual nodal disease in 37 (41.1%) patients (ypN1, n = 16 [17.8%]; ypN2a, n = 15 [16.7%]; and ypN2b, n = 6 [6.7%]). DFS differed significantly by postoperative nodal status (global log-rank p &lt; 0.001), with progressively poorer outcomes with increasing residual nodal burden. Conclusions: Residual nodal disease after neoadjuvant chemoimmunotherapy and surgery is associated with progressively inferior DFS according to its anatomic extent. The UICC\/AJCC 9th-edition staging system provides clinically relevant prognostic granularity, supporting further investigation of mediastinal restaging and postoperative treatment strategies.<\/jats:p>","DOI":"10.3390\/cancers18172871","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:23:37Z","timestamp":1788773017000},"page":"2871","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Residual Mediastinal Nodal Disease After Neoadjuvant Chemoimmunotherapy for Non-Small Cell Lung Cancer"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9805-9733","authenticated-orcid":false,"given":"Berta","family":"Mosleh","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Comprehensive Center for Chest Diseases, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5479-4649","authenticated-orcid":false,"given":"Anastasia","family":"Papaporfyriou","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Comprehensive Center for Chest Diseases, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Division of Pulmonology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5356-6452","authenticated-orcid":false,"given":"Thorsten","family":"Fuereder","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Comprehensive Center for Chest Diseases, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Division of Oncology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6119-6364","authenticated-orcid":false,"given":"Helmut","family":"Prosch","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Comprehensive Center for Chest Diseases, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9972-6690","authenticated-orcid":false,"given":"Joachim","family":"Widder","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Comprehensive Center for Chest Diseases, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Radiation Oncology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Felicitas","family":"Oberndorfer","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Comprehensive Center for Chest Diseases, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7787-991X","authenticated-orcid":false,"given":"Clemens","family":"Aigner","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Comprehensive Center for Chest Diseases, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Marco","family":"Idzko","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Comprehensive Center for Chest Diseases, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Division of Pulmonology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Daniela","family":"Gompelmann","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Comprehensive Center for Chest Diseases, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Division of Pulmonology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7088-8768","authenticated-orcid":false,"given":"Mir Alireza","family":"Hoda","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Comprehensive Center for Chest Diseases, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/j.annonc.2021.08.1994","article-title":"Early and locally advanced non-small-cell lung cancer: An update of the ESMO Clinical Practice Guidelines focusing on diagnosis, staging, systemic and local therapy","volume":"32","author":"Remon","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1016\/j.chest.2023.11.042","article-title":"Recurrence-Free Survival in Patients With Surgically Resected Non-Small Cell Lung Cancer: A Systematic Literature Review and Meta-Analysis","volume":"165","author":"Rajaram","year":"2024","journal-title":"Chest"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1016\/S0140-6736(07)60714-4","article-title":"Preoperative chemotherapy in patients with resectable non-small cell lung cancer: Results of the MRC LU22\/NVALT 2\/EORTC 08012 multicentre randomised trial and update of systematic review","volume":"369","author":"Gilligan","year":"2007","journal-title":"Lancet"},{"key":"ref_4","first-page":"611","article-title":"A systematic review and meta-analysis of the literature: Chemotherapy and surgery versus surgery alone in non-small cell lung cancer","volume":"1","author":"Burdett","year":"2006","journal-title":"J. Thorac. Oncol."},{"key":"ref_5","first-page":"CD006157","article-title":"Chemotherapy and surgery versus surgery alone in non-small cell lung cancer","volume":"2010","author":"Burdett","year":"2007","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_6","first-page":"305","article-title":"Adjuvant chemotherapy in patients with completely resected non-small cell lung cancer","volume":"3","author":"Pirker","year":"2014","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_7","first-page":"51","article-title":"Neoadjuvant and Adjuvant Immunotherapy in Early-Stage Non-Small Cell Lung Cancer","volume":"12","author":"Shukla","year":"2021","journal-title":"Lung Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhang, W., Liang, Z., Zhao, Y., Li, Y., Chen, T., Li, W., Chen, Y., Wu, P., Zhang, H., and Fang, C. (2024). Efficacy and safety of neoadjuvant immunotherapy plus chemotherapy followed by adjuvant immunotherapy in resectable non-small cell lung cancer: A meta-analysis of phase 3 clinical trials. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1359302"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1056\/NEJMoa2202170","article-title":"Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer","volume":"386","author":"Forde","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1056\/NEJMoa2302983","article-title":"Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer","volume":"389","author":"Wakelee","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1056\/NEJMoa2304875","article-title":"Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer","volume":"389","author":"Heymach","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1056\/NEJMoa2311926","article-title":"Perioperative Nivolumab in Resectable Lung Cancer","volume":"390","author":"Cascone","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1200\/JCO.21.02660","article-title":"Overall Survival and Biomarker Analysis of Neoadjuvant Nivolumab Plus Chemotherapy in Operable Stage IIIA Non-Small-Cell Lung Cancer (NADIM phase II trial)","volume":"40","author":"Provencio","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1056\/NEJMoa2502931","article-title":"Overall Survival with Neoadjuvant Nivolumab plus Chemotherapy in Lung Cancer","volume":"393","author":"Forde","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4292","DOI":"10.7150\/jca.119881","article-title":"The Prognostic Value of Lymph Node Downstaging Following Neoadjuvant Chemoimmunotherapy for Non-Small Cell Lung Cancer","volume":"16","author":"Guo","year":"2025","journal-title":"J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"43","DOI":"10.21037\/ccts-20-87","article-title":"Persistent N2 disease after neoadjuvant treatment...and now?\u2014The oncologist view","volume":"3","author":"Gautschi","year":"2020","journal-title":"Curr. Chall. Thorac. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"185","DOI":"10.18053\/jctres.07.202102.013","article-title":"Advances in multimodal treatment for stage IIIA-N2 non-small cell lung cancer","volume":"7","author":"Vila","year":"2021","journal-title":"J. Clin. Transl. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1055\/s-0042-1743433","article-title":"Survival Analysis of Surgically Resected ypN2 Lung Cancer after Neoadjuvant Therapy","volume":"71","author":"Isgorucu","year":"2023","journal-title":"Thorac. Cardiovasc. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12957-018-1313-x","article-title":"Comparing the benefits of chemoradiotherapy and chemotherapy for resectable stage III A\/N2 non-small cell lung cancer: A meta-analysis","volume":"16","author":"Chen","year":"2018","journal-title":"World J. Surg. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.21037\/jtd.2018.04.24","article-title":"Induction chemoradiotherapy versus induction chemotherapy for potentially resectable stage IIIA (N2) non-small cell lung cancer: A systematic review and meta-analysis","volume":"10","author":"Tong","year":"2018","journal-title":"J. Thorac. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e879","DOI":"10.1097\/MD.0000000000000879","article-title":"Is There a Survival Benefit in Patients With Stage IIIA (N2) Non-small Cell Lung Cancer Receiving Neoadjuvant Chemotherapy and\/or Radiotherapy Prior to Surgical Resection: A Systematic Review and Meta-analysis","volume":"94","author":"Xu","year":"2015","journal-title":"Medicine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2453825","DOI":"10.1080\/07853890.2025.2453825","article-title":"Prognostic significance of pathological response and lymph node status in neoadjuvant immunotherapy for potentially resectable non-small cell lung cancer","volume":"57","author":"Xu","year":"2025","journal-title":"Ann. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.cllc.2025.04.004","article-title":"Prognostic Implications of Lymph Node Status in Non-Small-Cell Lung Cancer Patients Before and After Neoadjuvant Chemoimmunotherapy: A Multicenter Retrospective Study","volume":"26","author":"Ma","year":"2025","journal-title":"Clin. Lung Cancer."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.jtho.2024.02.011","article-title":"The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groups in the Forthcoming (Ninth) Edition of the TNM Classification for Lung Cancer","volume":"19","author":"Nishimura","year":"2024","journal-title":"J. Thorac. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/j.jtho.2024.06.010","article-title":"Neoadjuvant and Adjuvant Treatments for Early Stage Resectable NSCLC: Consensus Recommendations From the International Association for the Study of Lung Cancer","volume":"19","author":"Spicer","year":"2024","journal-title":"J. Thorac. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"115426","DOI":"10.1016\/j.ejca.2025.115426","article-title":"Current perspective on resectability in stage III locally advanced NSCLC\u2014The thoracic surgeons\u2019 view","volume":"221","author":"Aigner","year":"2025","journal-title":"Eur. J. Cancer."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"108061","DOI":"10.1016\/j.lungcan.2024.108061","article-title":"An international and multidisciplinary EORTC survey on resectability of stage III non-small cell lung cancer","volume":"199","author":"Houda","year":"2025","journal-title":"Lung Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.jtho.2020.01.005","article-title":"IASLC Multidisciplinary Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy","volume":"15","author":"Travis","year":"2020","journal-title":"J. Thorac. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6427","DOI":"10.21037\/jtd-24-1011","article-title":"Pathological responses of primary tumor and lymph nodes in non-small cell lung cancer after neoadjuvant chemoimmunotherapy: A retrospective real-world study","volume":"16","author":"Shao","year":"2024","journal-title":"J. Thorac. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e70073","DOI":"10.1111\/1759-7714.70073","article-title":"Prognostic Significance, Radiological, and Metabolic Characteristics of Metastatic Lymph Nodes in Resectable Non-Small Cell Lung Cancer Following Neoadjuvant Chemoimmunotherapy","volume":"16","author":"Han","year":"2025","journal-title":"Thorac. Cancer."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Stefani, D., Pl\u00f6nes, T., Viehof, J., Darwiche, K., Stuschke, M., Schuler, M., and Aigner, C. (2021). Lung Cancer Surgery after Neoadjuvant Immunotherapy. Cancers, 13.","DOI":"10.3390\/cancers13164033"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15","DOI":"10.21037\/asj-21-77","article-title":"Thoracic surgical challenges after neoadjuvant immunotherapy for non-small cell lung cancer: A narrative review","volume":"3","author":"Minervini","year":"2023","journal-title":"AME Surg. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.jtcvs.2022.01.019","article-title":"Surgical outcomes after neoadjuvant nivolumab or nivolumab with ipilimumab in patients with non-small cell lung cancer","volume":"164","author":"Sepesi","year":"2022","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.ejcts.2006.08.008","article-title":"ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer","volume":"30","author":"Lardinois","year":"2006","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.lungcan.2005.01.001","article-title":"Complete resection in lung cancer surgery: Proposed definition","volume":"49","author":"Wittekind","year":"2005","journal-title":"Lung Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1097\/JTO.0b013e3181a0d82e","article-title":"The IASLC lung cancer staging project: A proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer","volume":"4","author":"Rusch","year":"2009","journal-title":"J. Thorac. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.annonc.2025.08.003","article-title":"Early and locally advanced non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"36","author":"Zer","year":"2025","journal-title":"Ann. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/17\/2871\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:36:15Z","timestamp":1788773775000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/17\/2871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,5]]},"references-count":37,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cancers18172871"],"URL":"https:\/\/doi.org\/10.3390\/cancers18172871","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,5]]}}}