Surgical treatment outcomes in patients with non-small cell lung cancer treated with neoadjuvant systemic therapy. A pilot single-center retrospective study

Objective: to evaluate the effectiveness of surgical treatment in patients with stage II–III non-small cell lung cancer, who received neoadjuvant systemic chemotherapy or chemoimmunotherapy, as well as to assess radiological and pathological tumor responses to drug therapy. Material and Methods. The study included 22 patients with stage IIB, IIIA and IIIB non-small cell lung cancer, who received neoadjuvant systemic therapy in the period from May 2022 to June 2024. Of these patients, 12 received platinum-containing chemotherapy (neoChT group) and 10 received chemoimmunotherapy including pembrolizumab (neoChIT group). The median number of therapy courses was 4 in each group. Radical surgery was performed in 7 patients from the neoChIT group and in 12 patients from the neoChT group. Results. Radiological complete response was observed in 1 patient from the neoChIT group, and partial response in 6 patients from the neoChIT group and in 7 patients from the neoChT group. Pathological complete response was observed in 3 patients from the neoChIT group and in 2 patients from the neoChT group. Lobectomy was the most common type of lung resection in both groups: in 5 patients from the neoChIT group and in 10 from the neoChT group. The majority of patients (60 %, 9/15) underwent sleeve lobectomies. Postoperative complications were recorded in 2 patients from the neoChIT group and in 4 from the neoChT group. Postoperative mortality in the group of radical surgeries was 5.3 % (1 out of 19). The follow-up period was 25.2 months. All patients who underwent surgery, excluding postoperative mortality, are alive. The 2-year recurrence-free survival rate was 77.4 ± 15.2 %. Disease progression 5 and 16 months after surgery was observed in 2 patients from the neoChT, respectively. Conclusion. Neoadjuvant systemic therapy is a safe and promising approach in the treatment of patients with locally advanced non-small cell lung cancer. The surgical component is characterized by a high frequency of organ-preserving interventions, a non-increased frequency of complications and satisfactory long-term results. The preliminary data obtained are comparable with the available data in the world literature. Unambiguous conclusions require further accumulation of experience and more extensive research.

1. Riely G.J., Wood D.E., Ettinger D.S., Aisner D.L., Akerley W., Bauman J.R., Bharat A., Bruno D.S., Chang J.Y., Chirieac L.R., DeCamp M., Desai A.P., Dilling T.J., Dowell J., Durm G.A., Gettinger S., Grotz T.E., Gubens M.A., Juloori A., Lackner RP., Lanuti M., Lin J., Loo B.W., Lovly C.M., Maldonado F., Massarelli E., Morgensztern D., Mullikin T.C., Ng T., Owen D., Owen D.H., Patel S.P., Patil T., Polanco P.M., Riess J., Shapiro T.A., Singh A.P., Stevenson J., Tam A., Tanvetyanon T., Yanagawa J., Yang S.C., Yau E., Gregory K.M., Hang L. Non-Small Cell Lung Cancer, Version 4.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2024; 22(4): 249–74. doi: 10.6004/jnccn.2204.0023.

2. Bott M.J., Yang S.C., Park B.J., Adusumilli P.S., Rusch V.W., Isbell J.M., Downey R.J., Brahmer J.R., Battafarano R., Bush E., Chaft J., Forde P.M., Jones D.R., Broderick S.R. Initial results of pulmonary resection after neoadjuvant nivolumab in patients with resectable non-small cell lung cancer. J Thorac Cardiovasc Surg. 2019; 158(1): 269–76. doi: 10.1016/j.jtcvs.2018.11.124.

3. Forde P.M., Spicer J., Lu S., Provencio M., Mitsudomi T., Awad M.M., Felip E., Broderick S.R., Brahmer J.R., Swanson S.J., Kerr K., Wang C., Ciuleanu T.E., Saylors G.B., Tanaka F., Ito H., Chen K.N., Liberman M., Vokes E.E., Taube J. M., Dorange C., Cai J., Fiore J., Jarkowski A., Balli D., Sausen M., Pandya D., Calvet C.Y., Girard N.; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable. Lung Cancer. N Engl J Med. 2022; 386(21): 1973–85. doi: 10.1056/NEJMoa2202170.

4. NSCLC Meta-analysis Collaborative Group. Preoperative chemotherapy for non-small-cell lung cancer: a systematic review and metaanalysis of individual participant data. Lancet. 2014; 383(9928): 1561–71. doi: 10.1016/S0140-6736(13)62159-5.

5. Wang H., Liu T., Chen J., Dang J. Neoadjuvant immunotherapy and neoadjuvant chemotherapy in resectable non-small cell lung cancer: A systematic review and single-arm meta-analysis. Front Oncol. 2022; 12: 901494. doi: 10.3389/fonc.2022.901494.

6. Wakelee H., Liberman M., Kato T., Tsuboi M., Lee S.H., Gao S., Chen K.N., Dooms C., Majem M., Eigendorff E., Martinengo G.L., Bylicki O., Rodríguez-Abreu D., Chaft J.E., Novello S., Yang J., Keller S.M., Samkari A., Spicer J.D.; KEYNOTE-671 Investigators. Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J Med. 2023; 389(6): 491–503. doi: 10.1056/NEJMoa2302983.

7. Lee J.M., Tsuboi M., Brunelli A. Surgical Perspective on Neoadjuvant Immunotherapy in Non-Small Cell Lung Cancer. Ann Thorac Surg. 2022; 114(4): 1505–15. doi: 10.1016/j.athoracsur.2021.06.069.

8. Liang W., Cai K., Chen C., Chen H., Chen Q., Fu J., Hu J., Jiang T., Jiao W., Li S., Liu C., Liu D., Liu W., Liu Y., Ma H., Pan X., Qiao G., Tian H., Wei L., Zhang Y., Zhao S., Zhao X., Zhou C., Zhu Y., Zhong R., Li F., Rosell R., Provencio M., Massarelli E., Antonoff M.B., Hida T., de Perrot M., Lin S.H., Di Maio M., Rossi A., De Ruysscher D., Ramirez R.A., Dempke W.C.M., Camidge D.R., Guibert N., Califano R., Wang Q., Ren S., Zhou C., He J. Expert consensus on neoadjuvant immunotherapy for nonsmall cell lung cancer. Transl Lung Cancer Res. 2020; 9(6): 2696–2715. doi: 10.21037/tlcr-2020-63.

9. Gentzler R.D., Riley D.O., Martin L.W. Striving toward Improved Outcomes for Surgically Resectable Non-Small Cell Lung Cancer: the Promise and Challenges of Neoadjuvant Immunotherapy. Curr Oncol Rep. 2020; 22(11): 109. doi: 10.1007/s11912-020-00969-w.

10. Nelson D.B., Mehran R.J., Mitchell K.G., Correa A.M., Sepesi B., Antonoff M. B., Rice D.C. Enhanced recovery after thoracic surgery is associated with improved adjuvant chemotherapy completion for non-small cell lung cancer. J Thorac Cardiovasc Surg. 2019; 158(1): 279–86. doi: 10.1016/j.jtcvs.2019.03.009.

11. Corsini E.M., Weissferdt A., Pataer A., Zhou N., Antonoff M.B., Hofstetter W. L., Mehran R.J., Rajaram R., Rice D.C., Roth J.A., Vaporciyan A.A., Walsh G. L., Cascone T., Heymach J.V., Swisher S.G., Sepesi B. Pathological nodal disease defines survival outcomes in patients with lung cancer with tumour major pathological response following neoadjuvant chemotherapy. Eur J Cardiothorac Surg. 2021; 59(1):100–8. doi: 10.1093/ejcts/ezaa290.

12. Albain K.S., Swann R.S., Rusch V.W., Turrisi A.T., Shepherd F.A., Smith C., Chen Y., Livingston R.B., Feins R.H., Gandara D.R., Fry W.A., Darling G., Johnson D.H., Green M.R., Miller R.C., Ley J., Sause W.T., Cox J.D. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet. 2009; 374(9687): 379–86. doi: 10.1016/S0140-6736(09)60737-6.

13. Chen T., Ning J., Shen J., Pan H., Fu L., Xu E., Wu H., Huang J., Yang Y., Li Z., Luo Q. Sleeve Lobectomy After Neoadjuvant Chemoimmunotherapy Versus Chemotherapy for Squamous Cell Lung Cancer: A Multicenter, Retrospective Study. JTO Clin Res Rep. 2023; 4(4): 100472. doi: 10.1016/j.jtocrr.2023.100472.

14. Hong T., Sun T., Zhang M., Liu X., Yuan Y., Dolo P.R., Chen B., Zhang H. Surgical perspective in neoadjuvant chemoimmunotherapy for stage II-III non-small cell lung cancer. Thorac Cancer. 2021; 12(20): 2796–2802. doi: 10.1111/1759-7714.14127.

15. Provencio M., Nadal E., Insa A., García-Campelo M.R., CasalRubio J., Dómine M., Majem M., Rodríguez-Abreu D., Martínez-Martí A., De Castro Carpeño J., Cobo M., López Vivanco G., Del Barco E., Bernabé Caro R., Viñolas N., Barneto Aranda I., Viteri S., Pereira E., Royuela A., Casarrubios M., Salas Antón C., Parra E.R., Wistuba I., Calvo V., Laza-Briviesca R., Romero A., Massuti B., Cruz-Bermúdez A. Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (NADIM): an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020; 21(11): 1413–22. doi: 10.1016/S1470-2045-(20)30453-8.

16. Chiappetta M., Tabacco D., Iaffaldano A.G., Evangelista J., Congedo M.T., Sassorossi C., Meacci E., D’Argento E., Bria E., Vita E., Tortora G., Boldrini L., Charles-Davies D., Massaccesi M., Martino A., Mazzarella C., Valentini V., Margaritora S., Lococo F. Clinical Stage III NSCLC Patients Treated with Neoadjuvant Therapy and Surgery: The Prognostic Role of Nodal Characteristics. Life (Basel). 2022; 12(11): 1753. doi: 10.3390/life12111753.

17. Felip E., Rosell R., Maestre J.A., Rodríguez-Paniagua J.M., Morán T., Astudillo J., Alonso G., Borro J. M., González-Larriba J.L., Torres A., Camps C., Guijarro R., Isla D., Aguiló R., Alberola V., Padilla J., Sánchez-Palencia A., Sánchez J.J., Hermosilla E., Massuti B.; Spanish Lung Cancer Group. Preoperative chemotherapy plus surgery versus surgery plus adjuvant chemotherapy versus surgery alone in early-stage non-small-cell lung cancer. J Clin Oncol. 2010; 28(19): 3138–45. doi: 10.1200/JCO.2009.27.6204.

18. Forde P.M., Chaft J.E., Smith K.N., Anagnostou V., Cottrell T.R., Hellmann M. D., Zahurak M., Yang S. C., Jones D.R., Broderick S., Battafarano R.J., Velez M.J., Rekhtman N., Olah Z., Naidoo J., Marrone K.A., Verde F., Guo H., Zhang J., Caushi J. X., Chan H.Y., Sidhom J.W., Scharpf R.B., White J., Gabrielson E., Wang H., Rosner G.L., Rusch V., Wolchok J.D., Merghoub T., Taube J.M., Velculescu V.E., Topalian S.L., Brahmer J.R., Pardoll D.M. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018; 378(21): 1976–86. doi: 10.1056/NEJMoa1716078.

19. Liang H., Yang C., Gonzalez-Rivas D., Zhong Y., He P., Deng H., Liu J., Liang W., He J., Li S. Sleeve lobectomy after neoadjuvant chemoimmunotherapy/chemotherapy for local advanced non-small cell lung cancer. Transl Lung Cancer Res. 2021; 10(1): 143–55. doi: 10.21037/tlcr-20-778.

20. Chaft J.E., Hellmann M.D., Velez M.J., Travis W.D., Rusch V.W. Initial Experience With Lung Cancer Resection After Treatment With T-Cell Checkpoint Inhibitors. Ann Thorac Surg. 2017; 104(3): 217–218. doi: 10.1016/j.athoracsur.2017.03.038.

21. Yang C.J., McSherry F., Mayne N.R., Wang X., Berry M.F., Tong B., Harpole D.H. Jr., D’Amico T.A., Christensen J.D., Ready N.E., Klapper J.A. Surgical Outcomes After Neoadjuvant Chemotherapy and Ipilimumab for Non-Small Cell Lung Cancer. Ann Thorac Surg. 2018; 105(3): 924–29. doi: 10.1016/j.athoracsur.2017.09.030.

22. Hu Y., Ren S.Y., Wang R.Y., Zeng C., Li J. N., Xiao P., Wu F., Yu F.L., Liu W.L. Surgical Outcomes After Neoadjuvant Chemoimmunotherapy for Resectable Non-Small Cell Lung Cancer. Front Oncol. 2021; 11: 684070. doi: 10.3389/fonc.2021.684070.

23. Thorsteinsson H., Alexandersson A., Oskarsdottir G.N., Skuladottir R., Isaksson H.J., Jonsson S., Gudbjartsson T. Resection rate and outcome of pulmonary resections for non-small-cell lung cancer: a nationwide study from Iceland. J Thorac Oncol. 2012; 7(7): 1164–69. doi: 10.1097/JTO.0b013e318252d022.

24. Hui B., Wang X., Wang X., Qiao B., Duan J., Shang R., Yang W., Wang J., Chen K., Yang F., Jiang T., Lei J. Organ preservation strategies after neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer: a multicenter retrospective cohort study. Int J Surg. 2023; 109(8): 2286–92. doi: 10.1097/JS9.0000000000000455.