ES22.02 A Milestone in Locally Advanced NSCLC

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Stage III NSCLC encompasses locally advanced tumours with infiltration of locoregional nodes and central thoracic structures and accounts for about a third of newly diagnosed NSCLC[1]. It represents the most advanced stage of NSCLC in which treatment is delivered with curative intent, but eventually more than 60% of patients die from their disease. Stage III NSCLC patients must strictly be discussed in a multidisciplinary tumor board, whereat the definition of resectability suffers from a certain heterogeneity across centers. Resectability is usually defined by the degree of invasion of lymph nodes, most often excluding multilevel or bulky N2 and N3 disease as well as invasion of the oesophagus, aorta and myocardium. Controversy exists on the role of surgery in stage III NSCLC since two large randomized trials investigated either induction chemoradiation therapy followed by resection versus radiotherapy[2], or induction chemotherapy followed by resection versus radiotherapy[3]. Both studies failed to demonstrate a difference in survival[2-5], however these treatment strategies are evidence-based and can be pursued in restectable NSCLC[6]. In the surgical scenario, randomised trials and meta-analyses have consistently shown that either adjuvant or neoadjuvant chemotherapy added to surgery results, with a better survival than surgery alone[7,8]. Adding preoperative radiotherapy to chemotherapy in patients with stage IIIA/N2 NSCLC did not improve the clinical outcome in a phase 3 randomised trial[9]. The role of adjuvant radiotherapy in stage IIIA/N2 after neoadjuvant chemotherapy followed by surgery has been evaluated in a unique randomized trial with awaited results (Lung ART, NCT00410683). Early NSCLC stages offer a theoretical unique curative scenario for the development of immunotherapy strategies, with limited disease volumes, a relative immune system preservation as well as unique opportunities for the investigation and assessment of new biomarkers. Perspectives, rational, hopes and ongoing attempts to combine immunotherapy in the surgical setting or alternatively complementary to chemoradiation will be discussed, with a focus on locally advanced disease. 1. Detterbeck FC. The eighth edition TNM stage classification for lung cancer: What does it mean on main street? J Thorac Cardiovasc Surg 2018;155:356-9. 2. Albain KS, Swann RS, Rusch VW, et al. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet 2009;374:379-86. 3. van Meerbeeck JP, Kramer GW, Van Schil PE, et al. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer. J Natl Cancer Inst 2007;99:442-50. 4. O'Rourke N, Roque IFM, Farre Bernado N, Macbeth F. Concurrent chemoradiotherapy in non-small cell lung cancer. Cochrane Database Syst Rev 2010:CD002140. 5. Auperin A, Le Pechoux C, Rolland E, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol 2010;28:2181-90. 6. Postmus PE, Kerr KM, Oudkerk M, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017;28:iv1-iv21. 7. Group NM-aC. Preoperative chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual participant data. Lancet 2014;383:1561-71. 8. Group NM-aC, Arriagada R, Auperin A, et al. Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data. Lancet 2010;375:1267-77. 9. Pless M, Stupp R, Ris HB, et al. Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial. Lancet 2015;386:1049-56. Stage III NSCLC , chemoradiation, neo-adjuvant immunotherapy