An Updated Review of Management of Resectable Stage III NSCLC in the Era of Neoadjuvant Immunotherapy

Author:

Verma Saurav12ORCID,Breadner Daniel12ORCID,Mittal Abhenil3ORCID,Palma David A.24,Nayak Rahul25ORCID,Raphael Jacques12ORCID,Vincent Mark12

Affiliation:

1. Division of Medical Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 3K7, Canada

2. London Regional Cancer Program, London Health Sciences Centre, London, ON N6A 5W9, Canada

3. Division of Medical Oncology, Northeast Cancer Centre, Ramsey Lake Health Centre, Sudbury, ON P3E 5J1, Canada

4. Division of Radiation Oncology, Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 3K7, Canada

5. Division of Thoracic Surgery, Department of Oncology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 3K7, Canada

Abstract

Immune-checkpoint inhibitors (ICIs) have an established role in the treatment of locally advanced and metastatic non-small cell lung cancer (NSCLC). ICIs have now entered the paradigm of early-stage NSCLC. The recent evidence shows that the addition of ICI to neoadjuvant chemotherapy improves the pathological complete response (pCR) rate and survival rate in early-stage resectable NSCLC and is now a standard of care option in this setting. In this regard, stage III NSCLC merits special consideration, as it is heterogenous and requires a multidisciplinary approach to management. As the neoadjuvant approach is being adopted widely, new challenges have emerged and the boundaries for resectability are being re-examined. Consequently, it is ever more important to carefully individualize the treatment strategy for each patient with resectable stage III NSCLC. In this review, we discuss the recent literature in this field with particular focus on evolving definitions of resectability, T4 disease, N2 disease (single and multi-station), and nodal downstaging. We also highlight the controversy around adjuvant treatment in this setting and discuss the selection of patients for adjuvant treatment, options of salvage, and next line treatment in cases of progression on/after neoadjuvant treatment or after R2 resection. We will conclude with a brief discussion of predictive biomarkers, predictive models, ongoing studies, and directions for future research in this space.

Publisher

MDPI AG

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