Chest CT provides only anatomic clues for tumor involvement of mediastinal lymph nodes

(enlargement greater than 10 mm), as demonstrated in a recent meta-analysis of over 3,400 evaluable

patients, with a pooled sensitivity of 57% and specificity of only 82%. This meta-analysis also

demonstrated that FDG (18F-2-fluoro-2-deoxy-D-glucose)–positron emission tomography (FDG–PET)

scanning appears to provide increased sensitivity of 84% and specificity of 89% in over 1,100 patients

studied for the detection of mediastinal malignancy.45 Several single-institution and multi-institutional

prospective studies have also indicated the superior diagnostic accuracy of FDG–PET imaging.46–48

Although the overall sensitivity and specificity of FDG–PET staging was 61% and 84%, respectively,

there was a significant improvement with FDG–PET over chest CT in the detection of both hilar (N1)

lymph node (42% vs. 13%, p = 0.0177) and mediastinal (N2 and N3) tumor involvement (58% vs. 32%,

p = 0.004). Whereas FDG–PET scanning can increase the suspicion of malignancy, its negative

predictive value for mediastinal lymph node involvement does not appear to be sufficient, with a falsenegative rate reported as high as 13%.49 PET evaluation of the solitary pulmonary nodule also appears

to be somewhat insensitive, with a negative predictive value for benign lesions of only 57%, indicating

a false-negative rate of 47%. Reliance on this modality could lead to delayed treatment for resectable

early-stage (IA) NSCLC.50 Integrated CT–PET imaging, in which concurrently performed chest CT

provides anatomic correlation for positive PET findings, appears to provide more precise staging,

particularly regarding tumor and nodal status,51 and also can be used to guide further invasive testing in

the accurate staging of lung cancer.

CLASSIFICATION

Table 79-3 TNM Classification for Staging System of Non–Small Cell Lung Cancer

(7th ed.)

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CLASSIFICATION

Table 79-4 The Mountain–Dresler Lymph Node Map

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Ultimately tissue confirmation of noninvasive findings should be obtained, particularly in the setting

of large, prospective trials being undertaken to determine the efficacy of neoadjuvant and adjuvant

therapy.52 Noninvasive techniques for clinical staging, particularly chest CT, have a reported falsenegative rate of approximately 10% to 15%. FDG–PET scan also has a reported false-positive rate of as

high as 50%.46 Clinical staging of NSCLC, particularly mediastinal lymph node involvement, can be

accomplished by needle aspiration techniques from several approaches: transbronchial (TBNA) with or

without endobronchial ultrasound (EBUS) guidance, transthoracic, or transesophageal. EBUS–TBNA is an

accurate method for evaluation of the mediastinum, comparable to, if not better than, the accuracy of

mediastinoscopy.53 Transesophageal endoscopic ultrasound with fine needle aspiration (EUS–FNA)

appears to be particularly useful for sampling of posterior mediastinal nodes such as the subcarinal,

periesophageal, or aortopulmonary window stations, particularly in patients with mediastinal

lymphadenopathy in these regions. Diagnostic yield is improved with practitioner experience, sampling

needle size and onsite cytology examination to determine adequacy of the obtained samples.

Cervical mediastinoscopy remains an important diagnostic modality, particularly for sampling of

smaller lymph nodes, or if larger sample sizes are needed either for assessment of tissue architecture, or

for supplemental molecular studies. This modality has a procedural sensitivity greater than 90%, and

specificity of 100%54 as demonstrated in a large retrospective review of a single-institutional

experience, including 1,745 patients, which demonstrated a reduction in “unnecessary” exploration, low

morbidity (0.6%) and minimal perioperative mortality (0.05%).55 For patients with clinically suspicious

aortopulmonary lymph node involvement (stations 5 and 6), an area which is generally not accessible

by standard mediastinoscopy, anterior mediastinotomy, extended cervical mediastinoscopy, or

thoracoscopy can be performed.

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RESULTS

Table 79-5 IASLC Lung Cancer Staging Project: Overall 5-Year Survival by Clinical

and Surgical 6th and 7th Edition TNM Stage

Patients presenting with suspected NSCLC and a pleural effusion should undergo thoracentesis,

followed by thoracoscopy, should initial cytology specimens be nondiagnostic. Those patients presenting

with metastatic (stage IV) disease involving a solitary distant site should obtain tissue confirmation at

the site of metastasis, if technically feasible. If noninvasive testing demonstrates multiple metastases

(e.g., multiple liver, brain, or bone lesions), then diagnosis of the primary lesion might provide the

most efficient means of diagnosis, followed by the initiation of palliative chemotherapy.56

Algorithm 79-1. Management of the incidental solitary pulmonary nodule. Partially based on MacMahon H, Austin JHM, Gamsu G,

et al. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society.

Radiology 2005;237:395–400.

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Algorithm 79-2. Evaluation of the patient who presents with a pulmonary mass.

Although newer modalities of noninvasive imaging, such as FDG–PET imaging, have improved the

accuracy of staging for lung cancer,8,49 these techniques still rely on factors such as tumor volume,

tumor density, and metabolic activity. Unfortunately, current staging procedures do not yet have the

sensitivity to detect all lymph node or distant hematogenous metastases.

Risk Assessment

Having established that resection is feasible, a significant number of patients with lung cancer cannot

undergo operation due to associated comorbidities that increase operative mortality and postoperative

morbidity. Age alone should not preclude patients with resectable disease from operation.57 In a

population with a high prevalence of prior or continuing tobacco use that has a greater predisposition to

atherosclerotic cardiovascular disease, preoperative cardiovascular risk assessment with further

noninvasive cardiac testing or coronary angiography, if indicated, should be considered.58

Preoperative spirometry, particularly the forced expiratory volume in 1 second (FEV1

), as an

assessment of patients’ suitability for pulmonary resection is essential. Measurement of the diffusing

capacity of the lung for carbon monoxide (DLCO) provides complementary data to standard spirometry,

particularly for patients with evidence of interstitial lung disease or exertional dyspnea. Generally, if a

patient demonstrates FEV1 >2 L (>60% predicted) or DLCO >50% predicted, further evaluation of

pulmonary capacity prior to resection is not necessary.59,60 Patients with limited pulmonary reserve,

including those with FEV1 <1.2 L (40% predicted) or DLCO 35% to 40% predicted, are at higher risk

for significant morbidity or mortality following anatomic resection, and should undergo further

evaluation.61

The predicted postoperative (ppo) lung function in patients with marginal pulmonary function can be

calculated as follows: ppoFEV1

(% predicted) = preoperative FEV1

(% predicted) × (1 – fraction of

total number of anatomic segments to be resected). Patients with ppoFEV1 <0.8 L, or 35% to 40%

predicted, are likely at substantially increased risk for perioperative death or complication.62,63 For

patients with heterogeneous lung disease including upper lobe predominant emphysema, quantitative

perfusion scanning provides a more accurate assessment. To obtain the ppoFEV1

(% predicted), the

preoperative FEV1

(% predicted) is multiplied by (100% – %perfusion of the area to be resected).

Preoperative room-air arterial blood gas testing can identify patients at greater risk for perioperative

complications or death. In particular, patients with arterial oxygen concentration less than 60 mm Hg,

PaCO2 greater than 45 mm Hg, or oxygen saturation less than 90% may be at greater risk for

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pulmonary resection.

If available, further testing with formal cardiopulmonary exercise testing (CPET) to calculate

maximal oxygen consumption (Vo2 max) may allow further risk stratification in such marginal patients.

In several series, patients with a Vo2 max <10 to 15 mL/min/kg were at high risk for postoperative

complication, whereas those with Vo2 max >20 mL/min/kg underwent operation without complication

or death.63 These findings were corroborated by a recent cooperative group study (CALGB 9238)

conducted to determine whether pulmonary resection could be accomplished safely in patients with

peak exercise oxygen capacity >15 mL/min/kg, regardless of FEV1

. In this prospective study of 346

patients who underwent thoracotomy for NSCLC, there were 86 subjects whose peak exercise oxygen

capacity was less than the threshold of <15 mL/min/kg, or 60% of predicted. This group experienced

significantly more cardiorespiratory complications, respiratory failure, or death than the remaining

subjects whose peak exercise oxygen capacity was >15 mL/min/kg. From these data, the authors

concluded that patients with peak exercise oxygen capacity >15 mL/min/kg, even if FEV1 and/or

DLCO were less than 70% predicted, could undergo pulmonary resection with curative intent.64

Algorithm 79-3. This algorithm illustrates the preoperative functional evaluation prior to lung cancer resection. FEV1

, forced

expiratory volume in 1 second; DLCO, carbon monoxide diffusing capacity; ppo, predicted postoperative values; Vo2 max,

maximum oxygen uptake.

Informal exercise testing, particularly stair-climbing, may also aid the clinician in determining a

patient’s suitability for resection. Patients who are able to climb at least two flights of stairs likely will

tolerate pneumonectomy, whereas those who cannot climb a single flight likely will not tolerate

lobectomy. Furthermore, oxygen desaturation, greater than 4%, during exercise testing may also be an

indicator for increased risk of perioperative complication. Careful preoperative physiologic assessment

will allow the clinician to identify patients at increased risk for perioperative complication or death, and

allow such patients to make an informed decision regarding operation.65 Measures to minimize

postoperative complications, including aggressive efforts to encourage smoking cessation, pre-and

postoperative chest physiotherapy, incentive spirometry, early extubation and mobilization, and the use

of postoperative thoracic epidural analgesia, are important for all patients undergoing pulmonary

resection, especially those with marginal pulmonary function (Algorithm 79-3).

Treatment

5 Pulmonary resection, with definitive tumor staging, remains the mainstay of treatment for stage I, II,

and selected stage III NSCLC. The extent of resection, segmentectomy, lobectomy, bilobectomy, or

pneumonectomy, is determined by the location and size of the primary tumor and also whether adjacent

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bronchopulmonary nodes are involved. At operation, tumor extent is evaluated by examination of the

parietal pleura, pericardium, and mediastinal structures. Complete resection must achieve

microscopically negative bronchial and vascular margins. Potential postoperative complications after

pulmonary resection are listed in Table 79-6.

COMPLICATIONS

Table 79-6 Postoperative Complications after Pulmonary Resection

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Figure 79-1. A: Posteroanterior chest radiograph shows an elevated left hemidiaphragm, suggestive of phrenic nerve involvement

by the mass. B: Lateral chest radiograph shows extension of the mass into the anterior chest wall (arrows). C: Computed

tomography suggests both pericardial and chest wall involvement (arrows). At thoracotomy, the chest wall, phrenic nerve, and

pericardium were found to be involved. All were resected en bloc with the tumor.

If a tumor extends directly into the chest wall, diaphragm, or pericardium, an en bloc resection of the

adjacent involved structure should be performed with the pulmonary resection. Reconstruction is

performed as necessary (Fig. 79-1). If extensive endobronchial involvement is present without

involvement of the surrounding vascular or lymphatic structures, the tumor can sometimes be removed

completely by lobectomy with segmental resection of the bronchus and/or pulmonary artery

(bronchovascular sleeve resection), thus preserving lung function.

Patients with centrally located tumors should undergo sleeve lobectomy rather than pneumonectomy

if complete resection can be achieved and such an approach is technically feasible. Several retrospective

studies

66–70 have demonstrated that operative mortality is reduced among patients undergoing sleeve

lobectomy (0% to 5.2%) when compared with patients undergoing pneumonectomy (1.7% to 8.9%).

Moreover, overall 5-year survival is improved among patients undergoing sleeve resection, particularly

among those with N0 or N1 nodal status. For peripherally located clinical stage I tumors, particularly

among patients with limited pulmonary reserve or those at high risk from other comorbidities,

segmental or nonanatomic “wedge” resection can be performed. Sublobar resection also may be

appropriate for patients with good pulmonary function and who otherwise would be candidates for

lobectomy (Table 79-7). Whether such patients are at greater risk for locoregional recurrence, as

suggested in earlier series

71–73 but not borne out in modern series,74 is under investigation in an

ongoing multi-institutional prospective and randomized cooperative group clinical trial (CALGB

140503).

Although noninvasive techniques for preoperative assessment of mediastinal nodes have improved,

nodal status should be confirmed by intraoperative mediastinal lymph node sampling or mediastinal

lymph node dissection. Accurate pathologic staging provides not only prognostic information but is also

important in the decision on whether to proceed with adjuvant chemotherapy. Systematic sampling

should include tissue from at least three N2 lymph node stations, using standard nomenclature and

numbering as depicted in (Table 79-4). Complete mediastinal lymph node dissection does not appear to

confer increased perioperative morbidity75 but also does not confer a survival advantage for patients

with early stage (T1, T2, N0, and N1) NSCLC as staged at the time of lung resection. The long-term

survival impact of mediastinal lymph node dissection has not been evaluated well for patients with

clinical staging obtained solely by radiography or for patients with higher-stage NSCLC.76–78

INDICATIONS

Table 79-7 Criteria for Sublobar Pulmonary Resection

Survival

Long-term survival after resection for NSCLC is linked to the pathologic stage of disease. The overall 5-

year survival rates are shown in Table 79-5. They range from 60% to 70% for stage I tumors, from 40%

to 50% for stage II tumors, and from 15% to 30% for stage IIIA tumors. Nodal involvement has the

strongest adverse influence on survival. Large peripheral tumors that extend directly into the chest wall

without nodal involvement (T3N0) are associated with a 5-year survival rate of 40% after complete

resection, whereas involvement of mediastinal nodes is associated with only a 20% survival rate.

Some series suggest that histology also affects survival. In node-negative NSCLC, large cell

neuroendocrine differentiation conferred worse survival than other types of NSCLC.79 Different

adenocarcinoma subtypes, particularly in more advanced tumors, also appear to confer worse prognosis,

but the influence of histology has not been described uniformly in series to-date.80 Delineation of tumor

biology by more refined histologic and molecular analyses will be needed to define which patients

might be at increased risk for recurrence or treatment resistance.

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