2. Surgical Strategies

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Patients with several comorbidities and limited functional reserve that contraindicate lobectomy, so as to allow them to be eligible for surgical treatment in early-stage NSCLC while accepting the compromise of a lower long-term survival. This class of patients is also influenced by the surgical technique chosen, with better post-operative recovery with minimally invasive techniques such as video-assisted (VATS) or robot-assisted (RATS) thoracotomy.

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In the case of early diagnosis, following the criteria indicated below, even for patients without comorbidities.

As also indicated by the 2023 NCCN guidelines for NSCLC ^[7], sublobar resections should be performed in the following case: a single tumor located in the outer third of the parenchyma, NSCLC suspected, clinical stage IA ^[8], size less than 2 cm in its largest diameter, C/T ratio < 0.5 evaluated using the lung window at CT scan, no lymphnode metastasis.

2.1. Nodule Localization

A crucial point in assessing the feasibility of sublobar resections, both wedge and anatomical, is the size and location of the lesion, which must be a single peripheral nodule, smaller than 2 cm in its largest diameter (considering both the solid component and the associated GGO component). A peripheral lesion is a nodule whose center is in the outer third of the lung parenchyma. This is so that the resection can be technically executable with adequate oncological margins. This type of resection is therefore not applicable for the centroparenchymal nodules.

2.2. Consolidation/Tumor Ratio

With the increasing use of imaging techniques in diagnostic examinations and the availability of low-dose CT devices, the diagnosis of early-stage lung lesions has increased. Based on radiological findings, evaluated using the lung window at CT scan, lung lesions can be classified as follows: pure ground glass nodules (GGN), part-solid nodules, and pure solid nodules. GGO is a descriptive term for a nonspecific radiologic finding that refers to an area of increased attenuation in the lung without blockage of the underlying pulmonary vessels or bronchial structures, whereas in pure solid nodules these underlying structures are no longer visible. In non-mucinous adenocarcinomas of the lung, these lesions (GGO vs. solid opacities) are associated with a lepidic or invasive pattern. This correlation is not absolute and several studies have been performed to discover predictive elements based on radiological finding [9,10,11,12,13]^{[9][10][11][12][13]}. The pathological patterns of growth of sub-solid nodules, including pure and partially solid GGN types and pure solid lesions, are obviously different, leading to different prognoses. As expected, sub-solid nodules with the GGO component have a good prognosis; conversely, pure solid lesions are thought to have high invasiveness with a worse prognosis [10,11]^[10][11]. The results of the JCOG0201 prospective study ^[13], which showed a consolidation/tumor ratio (CTR) < 0.5 (5-year relapse-free survival 95.9%) ^[14] as an evaluation criterion for non-invasive lung adenocarcinoma <2.0 cm with a specificity of 98.7% (95% CI: 93.2–100.0%), appear important in this context and this criterion could be used to radiologically define early adenocarcinoma of the lung. CTR was defined as the ratio of the maximum consolidation diameter (C) divided by the maximum tumor diameter (T), which was determined digitally based on the CT scan findings (using the lung window).

2.3. Oncological Margins

The main criticism of sublobar resection (especially in complex segmentectomies) is the smaller extension and amplitude of the parenchymal margins than in a standard lobectomy ^[15]. For this reason, nodule size and location are the main criteria to be analyzed. Sublobar resections such as anatomical segmentectomies and wedge resection should achieve parenchymal resection margins ≥ 2 cm or bigger than the size of the nodule ^[7]. The correct distance between the tumor margin and the resection margin should be closely examined in the pre-operative period by evaluating all CT scans (i.e., axial, sagittal, coronal views) including, if possible, 3D reconstruction ^[16] and intra-operatively confirmed with a frozen section. When required, surgical margins have to be widened to grant the best oncological outcome.

2.4. Complex and Simple Segmentectomy

A proper evaluation of the segmental anatomy of the lung is essential for planning the procedure. Although each segment has a different shape, they can generally be considered pyramidal, with the apex pointing toward the hilum. In the CT study, the segments can be identified by following the bronchial and vascular branches, flowing up and down the axial sections. Compared with the bronchial tree branches, evaluation of arterial and venous branches may be more complex because of their anatomic variability and the fact that more arteries may spray the same segment, whereas more veins may provide drainage. From a surgical perspective, anatomic segmentectomies are currently divided into simple and complex procedures ^[17]. Simple segmentectomies include resection of the apical segment of the lower lobe (both right and left), lingual segmentectomy, or left superior segmentectomy. Complex segmentectomies are anatomic sublobar resections that include segments other than those previously mentioned (Table 2). From a technical perspective, even when defined as “simple,” these anatomical structures are not always easy to identify and isolate. Compared to standard lobectomies, they require a longer learning curve. WResearchers could define a complex segmentectomy as the one that requires resection of more than one intersegmental plan (i.e., S2 or the S1–S2 bisegments in the right upper lobe) and, as referenced by many authors, are considered as a challenging resection even for a certified thoracic surgeon, also because the broncovascular structures are located deeper ^[18]. The complexity of this procedure is demonstrated by higher Prolonged Air Leak (PAL) rates and narrower surgical resection margins. Considering the previous paragraph, the correct location of the nodule is crucial in order to ensure adequate resection margins, especially for complex segmentectomies ^[19]. [Table 1].

Table 2. Simple and complex segmentectomy.

	Simple Segment	Complex Segment
Left Upper Lobe	Lingulectomy
	Upper Division
		1 + 2
		2
		3
Left Lower Lobe	6
	Basal Pyramid
		8
		9
		8 + 9
		9 + 10
		6 + 10
Right Upper Lobe		1 + 3
		1
		2
		3
Right Lower Lobe	6
	Basal Pyramid
		7
		8
		10
		8 + 9
		6 + 10
		9 + 10

2.5. Lymphadenectomy

As described previously, sublobar resections can be indicated for selected patients with clinical stage IA NSCLC, so pre-operative examination with CT and PET-CT should exclude nodal involvement. In the event that CT examination shows enlargement of mediastinal lymph nodes or PET-CT examination shows hyperactivity of lymph nodes, endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) or mediastinoscopic biopsy must be performed. Segmental lymph node dissection for intra-operative frozen section examination should be performed according to ESTS guidelines, and, as it was recently shown by the JCOG0802 and CALGB trials, absence of metastases in hilar and mediastinal lymph nodes has to be demonstrated as far as possible ^[20]. The importance of lymphadenectomy and its extension (considering N1 hilar lymph node stations, or N2 mediastinal nodes) are a subject of discussion since lesions that can be applied to this type of resection must be early-stage, node negative. For lobectomies, adequate lymph node dissection, including both hilar and mediastinal nodes, has been shown to be essential to ensure local disease control and to ensure proper staging ^[21]. In recent years some studies have tried to define this point for sublobar resections ^[22]. Handa et al. ^[23], in their multicenter, propensity-score-matched analysis, compared segmentectomies associated with hilar lymphadenectomy with those associated with mediastinal lymphadenectomy and concluded that a well-performed segmentectomy also requires a mediastinal lymphadenectomy, as this procedure allows the harvest of more lymph nodes and provides a more appropriate pathological staging compared to segmentectomies followed only by hilar lymphadenectomy.

2.6. Vats and Rats Resections

Sublobar resections and minimally invasive surgery are evolving together as they share a common goal, that is, to perform a proper and oncologically correct resection with an influence on patients’ post-operative quality of life that is as small as possible. Uniportal VATS resections are now performed all around the world with a standardized technique, although the learning curve is a little longer than that of standard VATS resections. In addition, robot-assisted resections are performed worldwide. RATS segmentectomies have similar post-operative outcomes compared to VATS resections in terms of post-operative complications, quality of life, and pain management, without any difference in oncological outcomes or number of lymph node stations resected. Furthermore, in RATS, the better visualization of the hilar structures of the lung segment often allows a more anatomically correct resection to be performed ^[24].