Surgical considerations in lung cancer treatment

CLINICAL PEARLS

Resectability is determined by patient fitness to undergo surgery and tumor characteristics.
Appropriate tumor staging, especially mediastinal nodal involvement, is fundamental to surgical planning.
Pulmonary function testing must be performed to determine whether a patient can tolerate loss of lung parenchyma safely.
Stage I/II disease is treated definitively with lobectomy, with adjuvant chemotherapy for select patient groups, and sublobar resection is reserved sublobar resection is reserved for small tumors, low risk histologies and patients with high morbidities.
Stage III disease has a heterogeneous presentation, and careful evaluation must be performed to determine which patients will receive oncological benefit from surgical intervention.

Introduction

Survival for patients with lung cancer remains poor, with all-comers experiencing less than 20% 5-year overall survival. Surgery remains fundamental to curative treatment of non−small cell lung cancer (NSCLC) and select patients with small cell lung cancer (SCLC). Decisions regarding resection may be complicated as a substantial proportion of lung cancer patients often have impaired pulmonary function as a result of smoking and chronic obstructive pulmonary disease (COPD). Selection of the appropriate surgical technique must balance minimization of surgical risk and optimization of oncological outcomes. In this chapter, we review the physiological and oncological principles associated with surgical planning for lung cancer resection.

Preoperative considerations

A patient-centered approach that incorporates patient values is important to the initial diagnosis and staging of lung cancer, as well as subsequent therapeutic decision making. In patients presenting with suspected lung cancer, the objectives of initial patient assessment are to determine the histological subtype, characterize the extent of disease, and evaluate for presence of comorbid medical conditions that may impact choice of treatment.

Staging

The tumor, node, metastasis (TNM) staging system provides a framework to describe patients with lung cancer by extent of disease, providing a specific stage, which is then used for prognostication and treatment selection. Unfortunately, only 25% of patients will present with resectable disease. The AJCC 8th edition of the TNM classification went into effect in January 2018 ( Table 4.1 ).

TABLE 4.1 ■

Summary of AJCC 8th Edition of Tumor Node Metastasis Staging for Lung Cancer ^a

T: Primary Tumor

T0 No evidence of primary tumor

Tis Carcinoma in situ

T1 ≤3 cm without main bronchus involvement

T2 >3 cm but ≤5 cm or

Involvement of main bronchus or visceral pleura or

Atelectasis or obstructive pneumonitis

T3 >5 cm but ≤7 cm in greatest dimension or

Separate primary tumor in same lobe or

Invasion of chest wall (including superior sulcus), phrenic nerve or parietal pericardium

T4 >7 cm or

Tumor nodule in separate ipsilateral lobe or

Invasion of diaphragm, mediastinum, heart, great vessels, trachea, esophagus,

recurrent laryngeal nerve, vertebral body or carina

N: Regional Nodal Involvement

N0 No regional nodal metastasis

N1 Ipsilateral peribronchial and/or hilar and intrapulmonary nodal metastasis

N2 Ipsilateral mediastinal and/or subcarinal nodal metastasis

N3 Contralateral nodal metastasis or

Ipsilateral or contralateral supraclavicular or scalene nodal metastasis

M: Distant Metastasis

M0 No Metastasis

M1 Distant Metastasis

Staging Summary

I Peripheral tumors ≤4 cm, N0

II Peripheral tumors ≤5 cm, N0

T3 N0

III T3 N1

T4 N any

T any N2-N3

IV any M

a Adapted from Detterbeck FC, Boffa DJ, Kim AW, Tanoue LT. Lung cancer stage classification. Chest . 2017;151(1):193-203.

Changes from the 7th edition predominantly included modifications to the T classification, including categorization of T1 into a to c on the basis of 1-cm increments. T2 now includes tumors measuring 3 to 5 cm, T3 includes diaphragm invasion and tumor size of 5 to 7 cm, and T4 is >7 cm. Mainstem bronchus involvement was downgraded from T3 to T2. N descriptors were carried from the 7th edition but include exploratory subclassifications based on the number of nodes involved. Finally, M staging has been updated to include an M1b classification that distinguishes oligometastatic disease from widespread systemic involvement.

Mediastinal nodal involvement

Assessment of mediastinal nodal involvement is an important component of staging that has a critical role in determining whether a patient is a candidate for surgical resection, as well as timing of surgery relative to other modalities of care (e.g., IIIA N2 disease, which may be treated with induction chemotherapy followed by surgical resection in select patients). Mediastinal staging includes both noninvasive and invasive approaches. All patients should undergo initial imaging with computed tomography (CT) and positron emission tomography (PET) scanning to evaluate the nodes of the chest. It is important that CT imaging also include the upper abdomen to assess the liver and adrenal glands, which may have positive findings in up to 10% of patients. Short-axis nodal diameter >1 cm is the most widely accepted criterion used to define suspicious abnormal mediastinal nodes seen on CT scan. Review of this cutoff, however, in 7368 patients demonstrated a median sensitivity and specificity of only 55% and 81%, respectively, thereby highlighting high false-positive rates, and that significant false-negative rates still occur (5%−15%). PET−CT imaging has a higher sensitivity and specificity for the evaluation of mediastinal adenopathy than CT alone (62% and 90%, respectively) and can provide important information regarding potential sites of extrathoracic metastasis. As such, it has an important role in staging. However, there is still a non-negligible false-positive rate highlighting the importance of pathological confirmation of metastatic disease.

All potentially resectable patients with clinical evidence of mediastinal nodal involvement on CT or PET are recommended to undergo pathological evaluation. Currently available methodologies for invasive pathological assessment of mediastinal nodal positivity include mediastinoscopy, mediastinotomy, endobronchial ultrasound (EBUS), or endoscopic ultrasound. The least invasive biopsy with the highest yield is generally the preferred modality. EBUS with fine-needle aspiration (FNA) may be used to assess the supraclavicular nodes (station 1) and superior mediastinal nodes (2−4 R/L) in addition to the subcarinal (station 7) and hilar/lobar nodes (N1 disease; stations 10−12). In addition to station 7, endoscopic ultrasound enables access to the subaortic (station 5), paraesophageal (station 8), and pulmonary ligament (station 9) nodes ( Fig. 4.1 ). CT-guided biopsy via transthoracic needle aspiration (TTNA) or anterior mediastinotomy (Chamberlain procedure) may provide additional access to the anterior nodal stations, including 5 and 6 (paraaortic). In addition to TTNA, a newer modality that may provide additional access to peripheral lesions is navigational bronchoscopy.

Fig. 4.1, Map of mediastinal lymph nodes.

In patients without pathological evidence of nodal disease resection should proceed as planned, recognizing that individuals with N1 disease will need chemotherapy postoperatively if not given as induction. If the biopsy is positive for N2 disease, patients may be treated with concurrent chemoradiation; however, select patients with N2 disease may be offered surgery as part of a multimodal treatment regimen (see N2 Disease later). In patients with negative CT/PET imaging, current guidelines from the National Comprehensive Cancer Network (NCCN) recommend that all patients with central tumors or clinical T1b-T4 lesions should undergo pathological evaluation of mediastinal nodes. Pathological mediastinal nodal evaluation before lung resection is considered optional in peripheral T1a disease. It should be noted, however, that up to 9% of patients with early-stage disease may harbor occult N2 disease, highlighting the importance of patient education and shared decision making.

Patient selection

Once patients are considered to be eligible for lung resection, the surgeon must perform a thorough evaluation of medical comorbidities and preoperative pulmonary function to assess the ability to tolerate surgery and loss of functional parenchyma following resection. Despite improvements in operative safety and outcomes, complication rates after lobectomy are significant with recent reported rates of 9.4% major morbidity and 1.3% mortality. Lung cancer shares many risk factors with COPD, and up to one third of patients with anatomically resectable disease may have prohibitive surgical risk as a result of severe pulmonary dysfunction.

Morbidity after surgery is related to pulmonary function and other factors such as American Society of Anesthesiologists and body mass index. It is important to ascertain the presence of any comorbid medical conditions in addition to functional capacity. Given that patients with COPD often have comorbid cardiac conditions, a full cardiovascular risk assessment should be performed. Importantly, current smoking habit independently predicts a 60% higher rate of morbidity and mortality after surgery. Smoking cessation counseling should be provided for all patients.

Pulmonary function testing

Forced expiratory volume (FEV) ₁ has traditionally been considered the key component of preoperative testing in patients scheduled to undergo lung cancer resection. FEV ₁ is a measure of pulmonary reserve that also correlates with the significance of respiratory impairment associated with COPD. Previous studies have demonstrated that FEV ₁ is an independent predictor of pulmonary morbidity and cardiovascular complications after pulmonary complications and that FEV ₁ <60% represents the best cutoff for predicting increased incidence of lung complications. ^, Guidelines from the British Thoracic Society have suggested that patients with preoperative FEV ₁ >2 L (>80% predicted) may tolerate pneumonectomy safely while those with FEV ₁ >1.5 L can tolerate lobectomy. The diffusing capacity of carbon monoxide (DLCO) has also been demonstrated to be an important predictor of survival after resection ( Fig. 4.2 ).

The American College of Chest Physicians (ACCP) currently recommends that both the preoperative FEV ₁ and the DLCO be measured with subsequent calculation of the predicted postoperative (PPO) values. In patients with PPO FEV ₁ and DLCO >60% predicted, no further testing is needed. If either value is <60% but both are above 30% predicted, a low technology exercise testing should be performed. This includes either stair climbing or a shuttle walk test. If either PPO FEV ₁ or DLCO is <30% (or the patient can walk <25 shuttles or climb <22 m), a formal cardiopulmonary exercise test should be performed with measurement of VO ₂ (maximal oxygen consumption), which correlates with the level of work achieved and is associated with postoperative complications. If VO ₂ max <10 mL/kg/min or <35% predicted on CPET, the patient should be counseled regarding a limited resection or nonoperative therapy. Such patients should also be considered for preoperative and/or postoperative pulmonary rehabilitation. See Fig. 4.3 for a summary of the ACCP recommendations for preoperative assessment of patients undergoing lung resection.

Fig. 4.3, Summary of the American College of Chest Physicians guidelines for the preoperative assessment of patients before undergoing a major lung resection. DLCO , Diffusing capacity of carbon monoxide; FEV , forced expiratory volume; PPO , predicted postoperative.

Operative procedures

Resection remains fundamental to curative treatment of lung cancer. The basic approach to every surgical resection includes confirmation of the diagnosis and stage, complete resection of the tumor, and clearance of locoregional lymphatic drainage through removal of lymph nodes. In patients without preoperative tissue biopsy, a wedge resection may be performed with frozen section pathological evaluation before formal resection.

Once resectability is determined, the tumor burden and patient characteristics determine the extent of surgery to be performed. This may be anatomical or nonanatomical. Anatomical resection involves resecting lung parenchyma in accordance with the branching of the pulmonary vessels and bronchi. This includes segmentectomy (single or multiple segments), lobectomy, bilobectomy, and pneumonectomy ( Fig. 4.4 ). In nonanatomical resection (wedge resection), the target lesion determines the extent of resection. A comprehensive nodal assessment must be performed in all pulmonary resections regardless of extent. This can include either systematic sampling or complete dissection. Further discussion of surgical management of lung cancer appears in Chapter 5 .

Fig. 4.4, The amount of lung removed at the time of surgery is tailored to both the patient and the tumor. Nomenclature used to define the type of resection performed is shown. (A) Wedge resection. A nonanatomical resection often reserved for removing small, peripheral nodules in patients with poor lung function. (B) Segmentectomy. An anatomical resection of one of the 19 pulmonary segments, increasingly used for lung-sparing resections of lung cancer. (C) Lobectomy. An anatomic resection of one of the five pulmonary lobes. It remains the standard for curative lung cancer surgery. (D) Sleeve resection. A reconstruction of the bronchus to spare a lobe not involved in tumor, thereby avoiding a pneumonectomy. (E) Pneumonectomy. Resection of an entire lung.

Lobectomy and pneumonectomy

Lobectomy, in which a single lobe is removed, has been the standard approach for patients with NSCLC. In patients with proximal disease involving mainstem bronchus, a sleeve lobectomy may be required. Traditionally, pneumonectomy, or removal of the entire lung on one side, was indicated for central disease; however, sleeve lobectomy has been demonstrated to have better morbidity and mortality with similar oncological safety. Bronchoplasty may be performed with a low risk of bronchial anastomotic complications. Currently, pneumonectomy is reserved for those patients who cannot be completely resected with bronchoplastic surgical approaches. In patients with right-sided tumors crossing the fissure or in cases where pneumonectomy would be poorly tolerated, a bilobectomy of the right middle lobe en bloc with either the upper or lower lobe may be performed.

Segmentectomy/wedge resection

Sublobar resection includes either segmentectomy, removal of one or more anatomic segments, or nonanatomic wedge resection ( Fig. 4.5 ). This treatment was initially reserved for patients who could not tolerate lobectomy as a result of poor pulmonary reserve or other extensive comorbidities as these limited resections demonstrated higher local recurrence. However, more recent data have suggested that there may be a role for sublobar resection in select patient populations (Sublobar resection discussed in greater detail on page 112).

Fig. 4.5, (A and B) Topographic anatomy of the bronchopulmonary segments of the left lung.

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