Rescue Surgery after Immunotherapy/Tyrosine Kinase Inhibitors for Initially Unresectable Lung Cancer

SIMPLE SUMMARY: Locally advanced or metastatic non-small cell lung cancer (NSCLC) has been considered for a long time as an unresectable disease. Chemotherapy was considered the only therapeutic option for these conditions and the results were unsatisfactory. Recent advances in biology and immunology have led to the use of personalized treatments by using tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), which produce significant and durable treatment responses. Large trials explored the utility of TKIs and ICIs in neoadjuvant or adjuvant settings, showing good results in terms of radiological response and long-term outcomes. Retrospective case series in patients with the previously unresectable disease who received treatment with TKIs, or ICIs showed important clinical changes that consider the possibility of pulmonary resection of the residual disease. They showed an overall feasibility for pulmonary resection but also raised concerns about the technical challenges. In the present study, we analyzed and reported the surgical and long-term outcomes of patients with initial unresectable, locally advanced, or oligometastatic NSCLC who were treated with TKIs or ICIs achieving a clinical downstaging so as to re-enter resectability. ABSTRACT: Background: We report the outcomes for unresectable patients with locally advanced or oligometastatic non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitor (TKI) or immunotherapy who achieved a clinical downstaging so as to re-enter resectability. Methods: We retrospectively reviewed the clinical, surgical, and pathological data of 42 patients with histologically proven, inoperable NSCLC who received rescue surgery after a good response to TKI or immunotherapy between March 2014 and December 2021. Results: Of 42 patients, 39 underwent pulmonary resection with therapeutic intent (three explorative thoracotomies). There were 26 males, with a median age of 64 years (range, 41–78 years). Twenty-three patients received TKIs and 19 immunotherapies. Anatomic resection was performed in 97.4% of resected patients (38/39) including 30 lobectomies, one right upper sleeve lobectomy, five pneumonectomies, one tracheal sleeve pneumonectomy, and one bilobectomy; a patient underwent wedge resection. Of 10 procedures attempted via a robotic approach, two required conversion to thoracotomy. No intraoperative morbidity/mortality occurred. The median operative time was 190 (range, 80–426) minutes; estimated blood loss was 200 mL (range, 35–780 mL). Morbidity occurred in 13/39 (33.3%). The median length of hospital stay was 6.5 days (range, 4–23 days). Pathologic downstaging was 74.4% (29/39). With a median follow-up of 28.7 months, the 5-year disease-free interval was 46.5%, and the 5-year overall survival was 66.0%; 32/39 patients (82.1%) are alive, 10 with the disease. Conclusions: Lung resection for suspected residual disease after immunotherapy or TKIs is feasible, with encouraging pathological downstaging. Surgical operation may be technically challenging due to the presence of fibrosis, but significant morbidity appears to be rare. Outcomes are encouraging, with reasonable survival during the short-interval follow-up.