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Preoperative Evaluation of Patients with Lung Cancer Undergoing Thoracic Surgery

Batra, Vikas MD; Kane, Gregory C. MD; Weibel, Sandra MD

Clinical Pulmonary Medicine: January 2002 - Volume 9 - Issue 1 - p 46-52
Topics In Pulmonary Medicine
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Surgery is currently the only potentially curative treatment modality for patients with early-stage non–small-cell lung cancer. Because of a high prevalence of chronic obstructive pulmonary disease in patients with lung cancer, they represent a special subset of patients for whom preoperative evaluation of cardiopulmonary status is especially important. The goal of preoperative evaluation of patients with lung cancer is to assess whether the neoplasm is surgically resectable and to estimate the risk of perioperative morbidity and mortality. Screening spirometry should be obtained in all patients. If the preoperative FEV1 is less than 60% of the predicted normal, predicted postoperative FEV1 (PPO-FEV1) should be estimated based upon the preoperative value and the functional contribution of the lung to be resected. Patients with PPO-FEV1 of more than 40% of predicted normal can tolerate pneumonectomy. In patients who appear borderline candidates for surgery based on static lung function criteria, cardiopulmonary exercise testing with measurement of maximum oxygen consumption (O2max) can further help stratify patients in terms of their risk for perioperative mortality or complications of surgical resection.

From the Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA USA

Address correspondence to: Gregory C. Kane, MD, Division of Critical Care, Pulmonary, Allergic and Immunologic Diseases, Thomas Jefferson University, Room 805 College, 1025 Walnut Street, Philadelphia, PA 19107. Address e-mail to: Gregory.Kane@mail.tju.edu.

Despite the recent advances in medical and radiation oncology, surgery remains an important treatment modality for patients with early-stage lung cancer. Almost all patients with lung cancer have a history of cigarette smoking, which puts them at risk for other important medical conditions such as chronic obstructive airway disease and coronary artery disease that may potentially affect operative risk. Thus, preoperative pulmonary evaluation is critical to assess the feasibility and risks of thoracotomy and to ensure the best possible outcome for these patients.

Modern surgical techniques have significantly reduced postoperative complications after thoracotomy. In the last few decades, mortality rate after pneumonectomy has decreased from a range from 10% to 15% to 3.2% to a range from 7.8% (1,2). Postoperative complications and mortality are lower with lobectomy or more limited resection. Higher rates are encountered in patients who are more than 70 years of age (2). Preoperative evaluation of a patient with lung cancer involves answering three questions: 1) is the neoplasm resectable? (anatomic resectability); 2) does the patient have adequate pulmonary reserve to tolerate pulmonary resection? (operability or physiologic resectability); 3) is there any major medical contraindication to the proposed surgery? The purpose of this article is to review the existing literature on preoperative pulmonary evaluation of patients with lung cancer undergoing thoracotomy. Although patients with lung neoplasm serve as prototypical cases, this analysis is intended to apply to the full spectrum of indications for thoracotomy and lung resection including benign and malignant neoplasms, infectious and inflammatory conditions, and vascular malformations.

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ANATOMIC RESECTABILITY

After a tissue diagnosis of lung cancer has been made, the neoplasm should first be assessed for anatomic resectability. A neoplasm is considered resectable if the entire tumor can be removed by surgery. Knowing the extent of tumor both within and outside the thorax is the key in determining resectability. The revised international system for staging divides patients into stages according to T (size and location of the primary tumor), N (regional lymph nodes involvement), and M (evidence of distant metastasis) descriptors (3). Once the T, N, and M status has been accurately assessed then the tumor can be staged (Table 1). Each of these stages has varying treatment options and survival expectations.

Table 1

Table 1

Surgical resection is considered the treatment of choice in physiologically operable patients with up to stage IIIA tumor. Patients with T4 primary tumor, i.e., tumor invading into heart, great vessels, trachea, esophagus, vertebral bodies, carina, or tumor with malignant pleural or pericardial effusion, are considered anatomically unresectable and these patients do poorly when such resections are attempted. To adequately stage non–small-cell lung cancer (NSCLC) it is necessary to examine regional lymph nodes within the mediastinum. Patients with metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene or supraclavicular lymph nodes (N3 disease) are inoperable. Treatment of patients with N2 disease is controversial. Historically, surgery was used in these patients with poor results. Patients with “bulky N2” disease tend to do poorly with surgery. Surgery still is indicated in patients with N2 disease that is detected only at the time of thoracotomy. In patients with bulky N2 disease, neoadjuvant (preoperative) chemotherapy combined with surgery has shown survival benefit in recent trials (4,5). Patients treated with neoadjuvant chemotherapy had an estimated median survival of 64 months as compared to 11 months for patients who had surgery alone (4). The accepted approach is that after a complete history and physical examination, a CT scan of the thorax from the lung apices down to the level of the adrenal glands is performed (6). If results of CT scan show no evidence of liver or adrenal involvement and no mediastinal adenopathy, invasive staging is not necessary for clinical stage I and II tumors. Because CT scan is sensitive but not highly specific for lymph node metastases, invasive staging is generally recommended when mediastinal adenopathy is present on CT to confirm the pathologic stage. Patients with proximal tumors should also be considered for invasive staging. Options for evaluation of mediastinal lymph nodes include transbronchial needle aspiration (TBNA), mediastinoscopy, lateral mediastinotomy, and intraoperative lymph node sampling. Wang and colleagues first reported the use of TBNA for staging bronchogenic carcinoma in 1982. TBNA can be used to sample paratracheal, subcarinal, bilateral hilar, and aortopulmonary lymph nodes. Mediastinoscopy involves passing a scope in front of trachea into the superior mediastinum. For sampling the aortopulmonary lymph nodes, an extended mediastinoscopy can be performed by passing the scope over the aortic arch at the base of the innominate artery or, alternatively, a left parasternal mediastinotomy incision (Chamberlain procedure) can be performed.

More recently, FDG-PET scan has shown a role in staging of lung carcinoma. Pieterman and colleagues studied 102 patients with resectable NSCLC. In their study, the sensitivity and specificity of PET for the detection of mediastinal metastases were 91% and 86%, respectively. The corresponding values for CT were 75% and 66%. PET scan also identified distant metastasis that had not been detected by standard methods in 11 of 102 patients (7). A disadvantage of PET scan is its limited anatomical resolution, which makes assessment of the extent of tumor unreliable. Furthermore, 18F-fluorodeoxyglucose accumulates as part of the physiologic process in the brain and the urinary tract, which makes evaluation of metastasis to these sites difficult. The high negative predictive value of PET scan may reduce the need for mediastinoscopy but at this time PET scanning is not universally available. Patients with distant metastasis (M1 disease) are considered unresectable, with one possible exception: the resection of the primary tumor in presence of a solitary brain metastasis (8,9). However, this situation has not been prospectively studied and remains controversial.

In summary patients with stage IA and IB, stage IIA and IIB, and selected stage IIIA NSCLC have surgically resectable disease. Patients with IIIA disease may have poor outcome with resection alone and should be considered for neoadjuvant chemoradiation prior to resection.

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OPERABILITY (PHYSIOLOGIC RESECTABILITY)

Physiologic Alterations After Thoracotomy and Lung Resection

If, after adequate staging, the tumor is found to be anatomically resectable, the next step is determination of operability or physiological resectability. To understand operability the physiologic changes due to surgery and the pulmonary reserve require discussion. When thoracic surgery is performed, several physiological effects occur. Even if no lung is resected, vital capacity declines by approximately 25% in the early postoperative period and slowly returns to baseline in a few weeks. Chest wall compliance also decreases to less than 50% and work of breathing increases to more than 140% of the preoperative level. The cough pressure is reduced to 30% of the preoperative value and increases to 50% by 1 week (10–12). Removal of lung parenchyma results in reduction of the pulmonary capillary bed and a decrease in vital capacity. The decrease in pulmonary capillary bed is well tolerated by patients with otherwise normal lungs but in patient’s with pulmonary dysfunction this may result in postoperative pulmonary hypertension. In patients with underlying lung disease, the reduction in vital capacity by lung surgery may result in acute and chronic respiratory failure, or even death. However, it should be noted that while in most circumstances lung resection leads to reduction in lung function, this is not always the case. Patients who undergo resection of large bullae may actually have improvement in lung function postoperatively because of better lung mechanics. On occasion, lung resection only involves removal of nonfunctioning lung parenchyma and there is little or no change in resultant lung function after recovery. Moreover, in some highly selected cases, in particular upper lobe tumors in patients with centrilobular emphysema, there may be a lung volume reduction surgery (LVRS)-like effect. In these selected circumstances, the resultant lung function after recovery from resection is actually better than the preoperative measurements. This effect is difficult to anticipate given the obvious important differences between lobectomy and LVRS protocols, but it has been noticed in anecdotal cases (13).

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Preoperative Evaluation

The initial step in preoperative evaluation is assessment of operative risk associated with a major surgical procedure. Prevention of postoperative complications requires a detailed medical history and examination. History should address the presence of dyspnea, exercise tolerance, cough, expectoration, wheezing, and smoking status. Examination should also focus on respiratory rate, pattern of breathing, wheezing, and body habitus. Patients with evidence of airway obstruction should be treated with bronchodilators and those with recent increase in sputum production or change in color of sputum may benefit from preoperative antibiotics. Smoking cessation should be advised to all patients. Abstinence from smoking will decrease carboxyhemoglobin acutely but improvement in mucociliary function and small airway obstruction may take up to 10 weeks (14). Stein and Cassara established that 3 weeks of smoking cessation combined with perioperative incentive spirometry in a group of patients undergoing nonthoracic general surgery improved outcomes (15). Three weeks of smoking cessation should be considered standard for all nonemergent major surgical procedures.

A unique consideration in patients considered for thoracotomy is the effect of pulmonary parenchymal resection on postoperative pulmonary function and exercise capacity. There is no single test that can reliably predict the patients’ likelihood of tolerating thoracotomy and lung resection without excessive postoperative morbidity and mortality. We review various tests that can be done to stratify patients according to their risk.

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Pulmonary Function Testing.

Most authors agree that simple spirometry is necessary as the initial screening test. Pulmonary function tests should be obtained when the patient is on maximal therapy for obstructive lung disease. Several studies have shown that patients with FEV1 more than 2 liters tolerate pneumonectomy (16–18). In typical cases, lobectomy can proceed when baseline FEV1 is greater than 1.0 liters (18). In patients of short stature, it is preferrable to use the FEV1 as a percent of predicted (more than 60% of predicted for pneumonectomy) rather than the absolute value.

Patients who appear marginal candidates for surgery by FEV1 criteria should undergo more detailed assessment of pulmonary function. Such additional tests include maximal voluntary ventilation (MVV) and single breath carbon monoxide diffusion capacity (DLCO). In a seminal study, Gaensler and coworkers showed a relationship between pulmonary function tests (PFT) and postoperative outcome (19). They studied 460 patients who underwent surgery for tuberculosis. They found that there was a 40% incidence of death due to pulmonary insufficiency in patients with maximum breathing capacity (MBC) (now called maximum voluntary ventilation, MVV) less than 50% of predicted and vital capacity (VC) less than 70% of predicted. In 1988, Ferguson and coworkers, in a retrospective study, found that the diffusion capacity of lung for carbon monoxide (DLCO) was the most important predictor of postoperative pulmonary complications and mortality. Patients with preoperative DLCO less than 60% of predicted had a 27% 30-day mortality as compared to 8% mortality for the group as a whole (20). Unlike spirometry and lung volumes, which test airway and bellows function, diffusion capacity assesses the basic gas exchange function of the lung. More recently, Ferguson and colleagues showed that predicted postoperative DLCO (PPO-DLCO) was a strong predictor of postoperative pulmonary complications and death (21). Patients with PPO-DLCO of greater than 40% of predicted tolerate pneumonectomy. They did not find any interrelationship between predicted postoperative FEV1 (PPO-FEV1) and PPO-DLCO, indicating that these values must be assessed independently, although Pierce and his colleagues noted that product of PPO-FEV1 and PPO-DLCO was more useful in predicting surgical mortality (22). It should be noted that none of these studies have been tested prospectively.

Various studies have shown that predicted postoperative FEV1 (PPO-FEV1) is an important correlate of postoperative mortality. The predictions are enhanced by expressing the value as a percentage of predicted rather than in absolute units (23,24). A number of tests have been used over the years to predict postoperative pulmonary function especially FEV1. For most patients simple calculation based on preoperative FEV1 and the amount of parenchymal resection contemplated provides a reasonable estimate of PPO-FEV1 (i.e., if preoperative FEV1 is 2 L then PPO-FEV1 after pneumonectomy is 1 L). The most logical approach to these calculations would entail counting the anticipated lung segments remaining after resection, dividing by 20, and multiplying by the FEV1. Based on the observation that COPD patients with FEV1 lower than 0.8L are more likely to be functionally impaired and/or hypercapnic, PPO-FEV1 of greater than 0.8 L or greater than 40% of predicted is considered essential (23–25).

Pulmonary parenchyma in diseased lung is not uniform and individual segments contribute varying function. So, in patients with borderline PPO-FEV1 based on simple calculations, certain additional tests that measure regional physiology may be required to quantitate the contribution of the lung requiring surgery and thus predict postoperative lung function. In the 1950s, a technique known as bronchospirometry was developed to assess unilateral lung function. In this procedure, a double-lumen endotracheal tube was used and each lumen was connected to a spirometer filled with 100% oxygen. The amount of oxygen uptake by each lung was a reflection of perfusion, and the volume of air exchanged during a vital capacity or MVV maneuver was a reflection of each lung’s ventilation. Postoperative lung function was predicted based on preoperative function and percentage of lung destined to remain (26). Lateral position testing is another method to evaluate unilateral lung function. This involves testing pulmonary function in supine and then right and left lateral positions. This process is no longer used in most centers because it is uncomfortable for patients and the results are inconsistent. A more accurate PPO-FEV1 can be obtained by measuring ventilation and perfusion in different parts of the lung via quantitative ventilation perfusion scan (quantitative V/Q scan) [PPO-FEV1 = (preopFEV1) × (% perfusion to the remaining lung)]. This is more accurate than an estimate based upon simple arithmetic using the number of segments resected. Ventilation is measured by using inhalation of xenon 133 gas and perfusion is measured using intravenously administered technetium 99m-labeled albumin macroaggregates. Wernly and coworkers utilized this technique to assess PPO-FEV1 with a mean percent error of less than 10% based on actual postoperative spirometry. More importantly, this technique identified 22 patients who underwent pneumonectomy despite preoperative FEV1 less than 2 L because PPO-FEV1 based on quantitative V/Q scan was greater than 1L. No death related to respiratory insufficiency was reported in this group. Various other studies have also shown the usefulness of quantitative V/Q scans in predicting postoperative lung function (27–30).

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Exercise Testing.

Exercise testing evaluates the interaction between heart, lung, vasculature and muscles. It provides an integrated view of fitness of the cardiovascular and respiratory systems, thereby providing a measure of global reserve. Historically such testing has its roots in stair climbing tests. Van Nostrand and colleagues used retrospective data from 91 pneumonectomies to correlate the two flight dyspnea test with mortality. They found that inability to climb two flights of steps was associated with a 30-day mortality of 50%. However, it failed to identify 9 of 11 postoperative deaths (31). The use of oxygen consumption (O2) parameters during exercise added a quantitative character to exercise testing and provided a measure of metabolic status. Eugene et al found that measurement of maximum oxygen consumption (O2max) on incremental cycle ergometer was a strong predictor of postoperative mortality (32). In this study, 75% of the patients with O2max less than 1 L died, and none of those with O2max greater than 1 L died. Expressing O2max in terms of mL/kg/min, which takes into account a patient’s body mass, increases the predictive power of the test. Smith and coworkers studied 22 patients prospectively using O2max, spirometry, split functions, and diffusion capacity. They discovered that O2max less than 15 mL/kg/min was associated with a 100% complication rate. Subjects with O2max between 15 and 20 mL/kg/min had a 66% complication rate and only one patient with a O2max greater than 20 mL/kg/min suffered a complication (33). In 1987, Bechard and Wetstein (34) studied 50 consecutive patients receiving a thoracotomy. Postoperative complications were present in 12% of the patients and overall mortality was 4%. Both of the two patients who died had O2max less than 10 mL/kg/min. 71.4% (5 of 7) of patients with O2max <10 mL/kg/min had cardiopulmonary complications compared to 10.3% (3 of 28) with O2max between 10 and 20 mL/kg/min. None of the patients with O2max greater than 20 mL/kg/min had any complications or death. More recently, Morice and colleagues reported success of lung resection in patients with O2max greater than 15 mL/kg/min who were deemed inoperable/high risk based on spirometry, quantitative V/Q scanning, and blood gas (35,36).

Thus, exercise testing is a useful complement to conventional cardiopulmonary evaluation in identifying patients who are at increased risk for post thoracotomy complications. It can also identify patients capable of tolerating surgery who might otherwise be considered inoperable.

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Blood Gas Analysis.

Pao2 and Paco2 are sometimes used as selection criteria for operability. Various studies have failed to identify any relationship between Pao2 and postoperative outcome (24). Improvement in ventilation perfusion mismatch after resection of tumors causing airway obstruction may be the reason. An elevation in Paco2 signifies marginal pulmonary reserve and increased likelihood of postoperative pulmonary complications. Traditionally clinicians have assumed that preoperative hypercapnia precludes lung resection by indicating chronic respiratory/ventilatory failure. However, more recent studies have demonstrated that hypercarbia lacks the predictive power for postoperative outcome when other parameters are used as selection criteria (35,37).

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Hemodynamic Studies.

Patients with compromised lung function may develop pulmonary hypertension and cor pulmonale after lung resection due to loss of pulmonary capillary bed. Measurement of pulmonary artery (PA) pressures has been examined as a preoperative indicator. Two measurements have been studied in detail: PA pressure measurements during temporary unilateral pulmonary artery occlusion and PA measurements during exercise.

Uggla studied 109 patients by unilateral PA occlusion. He reported that a mean pulmonary pressure of > 35 mm Hg was frequently associated with death postoperatively (38). Subsequent studies gave inconsistent results with low predictive value. This procedure is technically very demanding and is associated with significant risks. Therefore, owing to these problems, temporary unilateral pulmonary artery occlusion is not used in most hospitals as a preoperative assessment technique. Fee and colleagues evaluated the role of pulmonary vascular resistance during exercise (39). A Swan-Ganz catheter was passed to PA and then the exercise was used to uncover pulmonary hypertension not obvious at rest. They reported that calculated pulmonary vascular resistance (PVR) was most predictive of postoperative mortality. However, other studies do not confirm these conclusions. Lack of clear consensus and the invasive nature of the test have prevented widespread use of this test in preoperative evaluation of patients. Thus we do not recommend such tests as part of a routine preoperative evaluation.

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GENERAL MEDICAL EVALUATION

Other nonpulmonary factors such as cardiac disease must be considered prior to determination of operability. There have been several excellent reviews on this subject (40,41), and a detailed review of this literature is beyond the scope of this article. The decision to proceed with surgery for lung cancer must include consideration of these factors in terms of operative risk. In older patients an understanding of the natural history and expected survival is necessary in making individualized decisions.

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SUMMARY

Objective assessment of lung function is important for patients with lung cancer who are thought to be resectable. Whereas lobectomy or bilobectomy will spare more functioning lung tissue, it may be necessary to perform a pneumonectomy to completely resect a tumor. It is crucial to identify individuals who cannot tolerate resection, so that other forms of treatment that minimize loss of lung function can be offered as alternatives to surgery.

All patients with resectable NSCLC should undergo spirometry before a treatment plan is chosen. Spirometry alone may provide sufficient information to determine whether a lung cancer patient can undergo resection of lung tissue. If the FEV1 is greater than 2.0 L or greater than 60% of the predicted normal value, a pneumonectomy is likely to be tolerated. If the FEV1 is greater than 1.0 L, lobectomy is likely to be tolerated. In either case the predicted postoperative FEV1 should be greater than 0.8 to 1.0 liters or 40% predicted normal. Additional simple measurements that predict a patient’s ability to tolerate a pneumonectomy include a MVV greater than 50% of predicted normal value and DLCO greater than 60% of the predicted normal value (Table 2). If these data do not suggest a potentially safe resection, regional lung function assessment by quantitative radionuclide scanning can be utilized for more accurate predictions of the PPO-FEV1. Finally, exercise testing can provide the final determination of operative risk when other measures continue to reveal borderline results. The provided schema shown in the figure above can serve as an overview of the suggested assessment. It should be emphasized that while the provided schema can help categorize patients in terms of risk, no one study can predict surgical outcome. The challenge in managing these patients is to determine how the risk-benefit ratio applies to each individual patient.

Table 2

Table 2

Figure

Figure

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Keywords:

Lung neoplasm; Preoperative care; Pneumonectomy; Pulmonary function tests; Exercise test

© 2002 Lippincott Williams & Wilkins, Inc.