Short-term results of salvage surgery after immune and target therapies in non-small cell lung cancer

Background: In the last years, the knowledge about the non-small cell lung cancer (NSCLC) biology led to development of target therapies and immunotherapy. However, most indication were to advanced stages, with large nodal involvement or presence of distant metastases. However, the clinical response may be unpredictable, and in some cases, it is possible to see a large clinical response with resolution of the parameter that contraindicated surgical treatment. In these cases, surgery could be re-considered, performing a salvage surgery approach, but evidences regarding the feasibility of this approach in these clinical scenarios are still missing. The objective of this study is to describe the clinical, surgical and pathological characteristics of patients who underwent salvage surgery after target therapy or immunotherapy, for initially non-resectable NSCLC. Methods: Data of patients undergone salvage surgery after target therapy or immunotherapy from three different centres from January 1, 2015 to December 31, 2022 were retrospectively collected and analyzed. Results: The final analysis was led on 30 patients meeting inclusion criteria. Preoperatively, 22 patients presented stage III disease, 8 presented stage IV. For 22 patients without distant metastases, initial contraindication to surgery was due to bulky/multi-stations N2 involvement, advanced tumor (T) stage with concomitant N1/N2 involvement, N3 involvement. Target therapy mutations were anaplastic lymphoma kinase (ALK) rearrangement (treated with alectinib) and epidermal growth factor receptor (EGFR; treated with gefitinib, osimertinib and afatinib) in 8 total cases. Other 22 patients underwent immunotherapy alone or in association with chemotherapy in 4 cases. Surgery consisted mostly of lobectomy/bilobectomy (27 patients), and was considered feasible in all cases but 2, with local involvement. No peri-operative mortality was reported. Complications occurred in 6 (20%) and the length of stay was averagely 5.9±2.8 days. Pathological examination showed downstaging in 26 patients, with 11 (36%) patients that presenting pathological complete response (pCR). pCR occurred in 37% adenocarcinoma and 33% squamous cell carcinomas. Complete pathological response was observed in 10 out of 22 patients treated with immunotherapy, 1 patient treated with alectinib. Median follow up was 12 months. Five patients had recurrence and 4 died due to cancer related causes. Conclusions: Salvage surgery after target therapy or immunotherapy resulted to be a possible approach in selected patients.