Neoadjuvant treatment including immunotherapy followed by curative intent resection in patients with advanced NSCLC: initial institutional experience

Background:

In patients with stage III/IV non-small cell lung cancer (NSCLC), systemic treatment with or without radiotherapy is indicated and only selected patients may eventually benefit from surgery. Previous pilot studies showed that potentially resectable patients may benefit from neoadjuvant immunotherapy as it did not delay surgery and was associated with high rates of major pathological response. Moreover, immunotherapy leads to high response rates in patients initially deemed unresectable, which might increase the chance for successful surgery in these cases. Here we report our initial institutional experience for surgery after immunotherapy.

Material and method:

Patients with advanced NSCLC, who were initially deemed unresectable but showed major response to neoadjuvant immunotherapy (with or without chemo- and/or radiotherapy) and therefore underwent surgery were retrospectively analyzed. Primary endpoint was response to therapy and perioperative morbidity and mortality.

Result:

Five patients with stage III or stage IV lung adenocarcinoma received neoadjuvant immunotherapy followed by surgery. Three patients presented in stage IIIB and 2 patients in stage IV (1 oligometastatic with adrenal gland, 1 ipsilateral pleural carcinosis). Two patients received definitive chemo-radiotherapy combined with immunotherapy and 3 patients immunotherapy alone. All patients showed major clinical response and therefore were eligible candidates for surgery. In 2 patients, the definitive histology revealed a major and in 3 patients a complete pathological response with avital tumor cells and necrosis, ypT0N0. In this case study, the 30-day and 90-day mortality was 0% and no major postoperative complications were observed. All patients are tumor free after a median follow up of 8.5 months.

Conclusion:

Immunotherapy is currently investigated as a promising new option for neoadjuvant therapy and opens the door to radical surgery for patients with advanced NSCLC. In this case series, patients showed major response to induction immunotherapy, however the long-term results are still unclear. Notably, the real (pathological) response can only be determined after resection. This warrants well designed randomized controlled trials in this setting.