Does Induction Immunotherapy Confer Increased Operative Risk for Lung Resection?

Abstract

Promising and often durable initial results following immunotherapy for metastatic and advanced stage non-small cell lung cancer (NSCLC) have prompted researchers to evaluate the safety and efficacy of this approach for early and locally advanced resectable disease. The few published trials on this topic suggest that induction immune checkpoint inhibitor (ICI) monotherapy is safe. Results of multiple phase III studies show that doublet chemotherapy plus immune checkpoint inhibitor treatment is well-tolerated in patients with metastatic NSCLC. However, at present, no published trials have examined the safety and efficacy of induction immunotherapy with or without chemotherapy in this patient population. Although the published studies do not offer a definitive assessment of operative risk, multiple ongoing phase III trials of induction chemotherapy and immunotherapy are seeking to address this knowledge gap. Two key unanswered questions remain: What are the technical challenges incurred by the inflammatory response reported after induction immunotherapy? And does induction immunotherapy increase the perioperative risk associated with the use of immune checkpoint inhibitors as part of an induction strategy? Early findings, almost exclusively with ICI monotherapy, reveal a good pathologic response rate, with high rates of R0 resection. Anecdotal reports suggest surgical resections may be more technically challenging secondary to increased inflammation, fibrosis, and loss of normal tissue planes, particularly in the hilum and perivascular regions. Induction and adjuvant ICIs, either alone or, more likely, in combination with chemotherapy, are almost certainly going to be used for operable NSCLC in the future. Although the published data currently do not offer a definitive assessment of operative risk, we do not believe operative risk is substantively increased with monotherapy immunotherapy. Multiple ongoing phase III trials of induction chemotherapy and immunotherapy will definitively address this question by the mid-2020s.