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Page 2 of 10 Dolan et al. Mini-invasive Surg 2020;4:40 I http://dx.doi.org/10.20517/2574-1225.2020.17

≤ 1 cm to > 7 cm with nodal involvement ranging from none to metastases in the contralateral mediastinal
[3]
or hilar area, ipsilateral or contralateral scalene area, or supraclavicular lymph nodes . The new Stage
III subgroups were observed to have the following 5-year survival for clinical and pathologic staging,
[2]
respectively: IIIA 36% and 41%, IIIB 26% and 24%, and IIIC 13% and 12% .
This has led to an update in the clinical practice guidelines available to clinicians. The workup is the same
for all Stage III tumors including pulmonary function tests (PFTs), bronchoscopy, evaluation of mediastinal
[4]
lymph node evaluation, FDG PET/CT, and MRI or CT of the head . The difference lies in how to proceed
afterward. The European Society of Medical Oncology (ESMO) describes a three-pathway approach,
whereas the National Comprehensive Cancer Network (NCCN) guidelines describe many more options
[1,4]
for management based on the type of Stage III NSCLC cancer . ESMO focuses on nodal status based on
preoperative imaging and, while the NCCN guidelines start similarly, the nuance lies with T status, location
of primary tumor, presence of multiple tumors, N status, and determination of resectability. Both guidelines
are in general agreement that N3 patients and patients deemed unresectable proceed with non-surgical
multimodality treatment as their primary management. Incidental or occult N2 disease not previously
diagnosed remains a debated topic with NCCN stating that surgery can proceed and then use adjuvant
therapy or surgical resection can be halted and neoadjuvant treatment administered before definitive
[4]
[1]
resection . ESMO suggests proceeding with surgery and then adjuvant treatment . Both guidelines agree
that patients with N0-N1 disease can proceed to surgery first, with caveats in NCCN guidelines regarding
location in the thoracic cavity and presence of invasion.

Mediastinal staging is critical as the presence of N2 disease even with tumors of T stage T1a to T1c fall
[2]
into Stage IIIA . Staging techniques fall into the three broad categories: imaging, endoscopic, and surgical.
[5]
De Leyn et al. in their “Revised ESTS guidelines for preoperative mediastinal lymph node staging
for NSCLC” provided an overview of available techniques including Chest CT scan, PET-CT scan,
transbronchial needle aspiration, endoscopic ultrasound with aspiration, endobronchial-TBNA,
cervical mediastinoscopy, video-assisted thoracoscopic (VATS) biopsy, video-assisted mediastinal
lymphadenectomy, or transcervical extended mediastinal lymphadenectomy . The NCCN recommends
[5]
[4]
any patient suspected of having nodal disease to be biopsied by endoscopic or surgical means .
However, occult N2 disease can still be found even after these techniques. Risk factors that have been
identified with occult N2 metastases include larger tumor size and central location as well as high tumor
standardized uptake value seen on fluorodeoxyglucose (18F) PET/CT and tumor histology such as
[6-9]
adenocarcinoma with micropapillary features .

Our review aims to provide a summary of the latest body of knowledge on identification, medical treatment.
and surgical approaches to locally advanced NSCLC disease, with a focus on emerging minimally invasive
approaches to treatment including video-assisted thoracoscopic surgery and robotic-assisted lung resection.

An extensive literature search was performed by two independent co-authors. PubMed and Cochrane
Library were searched from their inception until December 2019. Published manuscripts regarding the
management of locally advanced NSCLC were reviewed with regards to the following: tumor characteristics
(size, location of tumor, metabolic activity, nodal involvement, clinical and pathologic staging, and final
histology), surgical vs. nonsurgical treatment, neoadjuvant or adjuvant therapy around surgery, extent of
resection (sublobar, lobectomy, and pneumonectomy), and method of resection (open, VATS, and robotic).
We also examined references of articles that we discovered using the previous criteria for additional studies
that may not have been found in our initial search. Additionally, articles deemed relevant and not identified
in the above-mentioned searches were included after review and consensus by the authors. We excluded all
studies that were case-reports, small case-series, or had questionable data analysis.