Surgery after neoadjuvant immunotherapy in patients with resectable non-small cell lung cancer

Abstract

Surgery is the standard of care for patients with operable non-small cell lung cancer (NSCLC). However, as a single modality, surgery for early stage or locally advanced NSCLC remains associated with high rates of local and distant recurrence. The addition of neoadjuvant or adjuvant chemotherapy has modestly improved outcomes. While systemic therapy paired with surgery for other malignancies such as breast cancer have resulted in far better outcomes for equivalent stage designations, outcome improvements for operable NSCLC have lagged in part as a result of trials where adjuvant chemotherapy seemed to incur harm for stage IA patients and only modest survival benefit for stage IB-IIIA patients (AJCC 7^th ed.). In recent years, immunotherapy for NSCLC has emerged as a systemic therapy with significant benefit over traditional chemotherapy regimens. These advances with immune checkpoint inhibitors (ICIs) have opened the door to administering peri-operative immunotherapy for operable NSCLC. As a result, a great multitude of studies investigating the use of immunotherapy in combination with surgery for NSCLC as well as several other malignancies have emerged. In this review, we outline the rationale for neoadjuvant immunotherapy in the treatment of operable NSCLC and summarize the available evidence that include preoperative ICI as a single modality or in combination with systemic agents and/or radiotherapy. Further, we summarize how such treatment trajectories open multiple unique windows of opportunity for scientific discovery and potential therapeutic gains for these vulnerable patients.

Keywords: Immunotherapy; carcinoma, non-small-cell lung; neoadjuvant therapy; thoracic surgery.

Figure 1

Heterogeneity of pathological responses in published neoadjuvant trials for NSCLC (77,85-91). Various pCR and MPR rates were published in recent neoadjuvant immunotherapy trials for operable NSCLC. The effect of the molecule itself and the technique used for response assessment are two important factors that could explain this phenomenon. NSCLC, non-small cell lung cancer; MPR, major pathological response; pCR, complete pathological response.

Figure 2

Process mapping of a patient with NSCLC. The patient’s trajectory from screening and diagnosis to post-operative course and survivorship is inevitably influenced by the treatment modalities, whether neoadjuvant or adjuvant, offered during the process itself. Neoadjuvant therapy leads to many informative and valuable opportunities for improvement, including risk factor modification, biomarker exploration, prehabilitation, nutrition optimization and scientific discovery. NSCLC, non-small cell lung cancer.