Downstaging and RATS After Neo-Chemo-IO: Impact on Surgical Outcomes in NSCLC

Official title

The Impact of Downstaging on Robotic Surgical Outcomes After Neoadjuvant Chemo-Immunotherapy in Non-Small Cell Lung Cancer

Overview

The goal of this observational study is to learn whether tumor and nodal downstaging after neoadjuvant chemo-immunotherapy is associated with better surgical outcomes in patients with clinical stage IIB-III non-small cell lung cancer (NSCLC) undergoing robotic-assisted thoracic surgery. The main question it aims to answer is: Is downstaging after neoadjuvant chemo-immunotherapy associated with better surgical outcomes in patients with stage IIB-III NSCLC undergoing robotic-assisted surgery? Participants with resectable or potentially resectable stage IIB-III NSCLC who receive neoadjuvant chemo-immunotherapy as part of their routine clinical care and then undergo curative-intent robotic-assisted surgery will be prospectively enrolled from international centers. Clinical, operative, pathological, and postoperative outcome data will be collected, including R0 resection, the extent of resection, conversion to open surgery, postoperative complications, length of stay, readmission, and mortality.

Detailed description

Please check all details of this study in Clinicaltrials.gov

Interventions

• Procedure Robotic-assisted surgery (RATS)
  Robotic pulmonary surgery for patients with neoadjuvant chemo-immunotherapy for stage IIB-III non-small cell lung cancer

Primary outcome measures

• Complete resection (R0 resection) [Time frame: From enrollment to the end of surgical treatment at 4 weeks]

Secondary outcome measures (6)

• Length of stay (LOS) [Time frame: From enrollment to the end of the whole treatment in the index hospitalization]
• Major postoperative complications [Time frame: From enrollment to the end of the whole treatment at 3 months]
• Conversion to open [Time frame: From enrollment to the end of surgical treatment]
• Extended procedures [Time frame: From enrollment to the end of surgical treatment]
• 30- and 90-day readmission rates [Time frame: From enrollment to the end of treatment at 3 months]
• 30- and 90-day mortality [Time frame: From enrollment to the end of treatment at 3 months]

Eligibility criteria

Inclusion criteria

• Age ≥18 years
• Histologically confirmed NSCLC
• AJCC 9th clinical stage IIB-III, M0, deemed resectable or potentially resectable by the multidisciplinary tumour discussion (MDT)
• Planned neoadjuvant chemo-immunotherapy (PD-1/PD-L1 inhibitor + platinum doublet; additional neoadjuvant RT is allowed) with curative-intent surgery
• Received ≥1 cycle of chemo-IO (capture the intended 2-4 cycles)
• Baseline chest CT±PET-CT within 6 weeks before starting neoadjuvant therapy
• Restaging 2-6 weeks after last neoadjuvant dose with chest CT±PET-CT
• Curative-intent resection planned; surgery performed 2-10 weeks after last dose
• Performing systematic nodal dissection
• ECOG performance status 0-2.
• Complete 90-day postoperative follow-up
• Ability to provide informed consent

Exclusion criteria

• Metastatic disease (M1) at baseline or on restaging
• No immunotherapy component in the neoadjuvant regimen (unless enrolled in a prespecified comparator cohort; otherwise exclude from primary analysis)
• Prior systemic therapy or thoracic radiotherapy for the current lung cancer before starting neoadjuvant chemo-IO
• Planned neoadjuvant chemoradiation (exclude unless including immunotherapy)
• Definitive decision against surgery before starting neoadjuvant therapy
• Active autoimmune disease requiring systemic immunosuppression within 2 years, prior organ transplant, or history of grade ≥2 pneumonitis/ILD
• Uncontrolled infection, pregnancy/lactation, or any condition precluding curative-intent resection per MDT

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 7 centers

• Fujian Medical University Union Hospital — Fuzhou
• Guangdong Provincial People's Hospital — Guangzhou
• Shenzhen People's Hospital — Shenzhen
• Jiangsu Cancer Institute & Hospital — Nanjing
• The Affiliated Hospital of Qingdao University — Qingdao
• Tianjin Medical University Cancer Institute & Hospital — Tianjing
• Shanghai Chest Hospital, Shanghai Jiao Tong University Medicine of School — Shanghai

France · 2 centers

• Hôpital Saint Joseph Marseille — Marseille
• University Hospital, Rouen — Rouen

Italy · 1 center

• Azienda Ospedaliera di Cosenza — Cosenza

Publications

• Sepesi B, Zhou N, William WN Jr, Lin HY, Leung CH, Weissferdt A, Mitchell KG, Pataer A, Walsh GL, Rice DC, Roth JA, Mehran RJ, Hofstetter WL, Antonoff MB, Rajaram R, Negrao MV, Tsao AS, Gibbons DL, Lee JJ, Heymach JV, Vaporciyan AA, Swisher SG, Cascone T. Surgical outcomes after neoadjuvant nivolumab or nivolumab with ipilimumab in patients with non-small cell lung cancer. J Thorac Cardiovasc Surg PMID 35190177
• Li X, Li Q, Zhao E, Yang F, Gao E, Lin L, Li Y, Hu X, Zhu Y, Zhao D, Fan J, Song X, Duan L. Perioperative Outcomes of Robotic- vs Video-Assisted Thoracoscopic Surgery in Non-Small Cell Lung Cancer After Neoadjuvant Therapy. Ann Thorac Surg. 2026 May;121(5):1184-1193. doi: 10.1016/j.athoracsur.2025.12.003. Epub 2025 Dec 26. PMID 41456828
• Herrera LJ, Schumacher LY, Hartwig MG, Bakhos CT, Reddy RM, Vallieres E, Kent MS. Pulmonary Open, Robotic, and Thoracoscopic Lobectomy study: Outcomes and risk factors of conversion during minimally invasive lobectomy. J Thorac Cardiovasc Surg. 2023 Jul;166(1):251-262.e3. doi: 10.1016/j.jtcvs.2022.10.050. Epub 2022 Nov 15. PMID 36509569
• Bott MJ, Yang SC, Park BJ, Adusumilli PS, Rusch VW, Isbell JM, Downey RJ, Brahmer JR, Battafarano R, Bush E, Chaft J, Forde PM, Jones DR, Broderick SR. Initial results of pulmonary resection after neoadjuvant nivolumab in patients with resectable non-small cell lung cancer. J Thorac Cardiovasc Surg. 2019 Jul;158(1):269-276. doi: 10.1016/j.jtcvs.2018.11.124. Epub 2018 Dec 13. PMID 30718052
• Veronesi G, Park B, Cerfolio R, Dylewski M, Toker A, Fontaine JP, Hanna WC, Morenghi E, Novellis P, Velez-Cubian FO, Amaral MH, Dieci E, Alloisio M, Toloza EM. Robotic resection of Stage III lung cancer: an international retrospective study. Eur J Cardiothorac Surg. 2018 Nov 1;54(5):912-919. doi: 10.1093/ejcts/ezy166. PMID 29718155
• Kneuertz PJ, Villamizar N, Altorki NK, Phillips JD, Schnorr P, Jones D, Scott S, D'Souza DM, Baiu I, Abdel-Rasoul M, Schmidt J, Nguyen DM, Merritt RE. Minimally invasive resection of non-small cell lung cancer after chemoimmunotherapy: A multicenter study in academic hospitals. J Thorac Cardiovasc Surg. 2025 Dec;170(6):1803-1812.e2. doi: 10.1016/j.jtcvs.2025.07.030. Epub 2025 Jul 25. PMID 40716726
• Hawkins A, Martin LW. Operative Challenges After Induction Immunotherapy for Lung Cancer. Thorac Surg Clin. 2025 Aug;35(3):285-298. doi: 10.1016/j.thorsurg.2025.04.002. Epub 2025 Jun 6. PMID 40619176
• Trabalza Marinucci B, Mancini M, Siciliani A, Messa F, Piccioni G, D'Andrilli A, Maurizi G, Ciccone AM, Menna C, Vanni C, Tiracorrendo M, Rendina EA, Ibrahim M. Surgical Techniques for Non-Small-Cell Lung Cancer After Neoadjuvant Chemo-Immunotherapy: State of Art and Review of the Literature. Cancers (Basel). 2025 Feb 14;17(4):638. doi: 10.3390/cancers17040638. PMID 40002233

Identifiers

NCT: NCT07528066 · IS26036

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗