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Review
. 2024 Mar 27;16(7):1302.
doi: 10.3390/cancers16071302.

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

Saurav Verma  1   2 , Daniel Breadner  1   2 , Abhenil Mittal  3 , David A Palma  2   4 , Rahul Nayak  2   5 , Jacques Raphael  1   2 , Mark Vincent  1   2
Affiliations
Review

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

Saurav Verma et al. Cancers (Basel). .

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.

Keywords: ICI; NSCLC; immune checkpoint inhibitors; immunotherapy; locally advanced; lung cancer; neoadjuvant; perioperative; resectable; stage III.

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Conflict of interest statement

M.V. reports serving on advisory boards or receiving consulting or lecture fees from Merck, Bristol Myers Squibb, AstraZeneca, Eli Lilly, Amgen, Apobiologix, Boehringer, Roche, Sanofi, and Pfizer. D.B. reports receiving honoraria from AstraZeneca, Bristol Myers Squibb, Takeda, Merck, Bayer, and Amgen for serving on advisory boards and speakers’ bureaus. J.R. reports receiving honoraria from Astra Zeneca, Merck, Novartis and Lilly Oncology for serving on advisory boards. The rest of the authors have no conflicts of interest.

Figures

Figure 1
Figure 1
Schema of phase II/III trials with neoadjuvant immune checkpoint inhibitors (ICIs) in patients with resectable NSCLC.
Figure 2
Figure 2
Potential options for salvage treatment.
Figure 3
Figure 3
Potential role of ctDNA as a biomarker in resectable NSCLC in the era of immunotherapy.
See this image and copyright information in PMC

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