Surgery after Induction Targeted Therapy and Immunotherapy for Lung Cancer

Abstract

Multimodality therapy for locally advanced non-small cell lung cancer (NSCLC) is a complex and controversial issue, especially regarding optimal treatment regimens for patients with ipsilateral positive mediastinal nodes (N2 disease). Many trials investigating neoadjuvant immunotherapy and targeted therapy in this subpopulation have shown promising results, although concerns have risen regarding surgical feasibility. A thorough literature review was performed, analyzing all recent studies regarding surgical morbidity and mortality. Despite the fact that two major trials investigating this subject were terminated early, the overall consensus is that surgical management seems feasible. However, dissection of hilar vessels may be challenging due to hilar fibrosis. Further research is necessary to identify the role of surgery in these multimodality treatment regimens, and to define matters such as the optimal treatment regimen, the dosage of the different agents used, the interval between induction therapy and surgery, and the role of adjuvant therapy.

The Role of Surgery in Lung Cancer Treatment: Present Indications and Future Perspectives—State of the Art

“…These pCR results are far superior to previous neo-adjuvant protocols [135] with controlled adverse events allowing better survivals, with 77% of 2-year DFS, and 90% of 2-year OS for stage IIA NSCLC. As reported by Allaeys et al [157] many trials reported acceptable safety and efficacy of neo-adjuvant immunotherapy with controlled adverse events and post-operative morbidity and a surgery performed on time without the need to postpone it. Bott et al [161] reported a higher rate of conversion to thoracotomy due to significant hilar inflammation and fibrosis which are the main surgical technical difficulty reported both in minimally invasive approach or for open procedures.…”

“…Recently Allaeys et al [157] have published a review reporting the latest data from trials and ongoing trials, concerning the short-and long-term postoperative follow-up of patients undergoing surgical resection after induction immunotherapy and/or targeted therapy with or without chemotherapy. In this review [157], surgery for a resectable locally advanced stage NSCLC after induction therapy including immunotherapy or targeted therapy with or without chemotherapy seems to be feasible and safe. Nevertheless, the lung resection could be more difficult with serious concerns due to hilar, vascular and bronchial fibrosis, but acceptable morbidity and mortality rates were reported in experienced centers.…”

“…Concerning neo-adjuvant targeted therapies, it seems to be a safe and effective treatment allowing major pathological response and pCR with controlled adverse events, and post-operative morbidity and mortality rates based on the reviews from Allaeys et al [157] and Li Sun et al [163]. Nevertheless, phase III trials are necessary to confirm these findings.…”

The role of endosonography-guided fine needle aspiration in preoperative restaging in the era of novel neoadjuvant therapies—a literature review

“…Currently, chemoradiotherapy is the treatment of choice for stage III (IIIA-N2/IIIB-N3) non-small cell lung cancer (NSCLC). However, selected patients with N2/N3 disease, particularly those with a disease responding considerably to induction chemotherapy, radiotherapy, chemoradiotherapy, targeted therapy, and/or immunotherapy may be candidates for surgical resection and mediastinal lymph node dissection (1,2). Persistence of mediastinal metastases after induction therapy generally denotes poor surgical outcomes (3)(4)(5).…”

Chimeric Antigen Receptor T-Cell Therapy in Lung Cancer: Potential and Challenges

“…The primary molecular-targeted therapies include epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), anti-EGFR monoclonal antibodies, fusion gene ALK and ROS1 inhibitors, and anti-vascular endothelial growth factor receptor monoclonal antibodies (9)(10)(11)(12). Combined therapy with multiple immune checkpoint inhibitors, such as a combination of nivolumab and ipilimumab, has been shown to achieve better response rates than monotherapy (13,14).…”