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Lung Cancer

Lung Cancer: Who is a Candidate for Surgery?: An Emerging Role for PET Scanning 
  Submitted By: Jules Lin, M.D.

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Lung Cancer: Who is a Candidate for Surgery?: An Emerging Role for PET Scanning


Authored by: Jules Lin, M.D.(1), Richard K.J. Brown, M.D. (2), and Andrew C. Chang, M.D. (3)





INTRODUCTION

Lung cancer is the leading cause of cancer death in the United States for both men and women and continues to have a five-year survival rate of less than 10%. Currently, complete surgical resection remains the best hope for cure. However, not all patients with lung cancer are candidates for surgical resection. This article describes the process used in selecting patients who are eligible for lung cancer resection. After determining that lung cancer is present, it is important to assess the resectability of the tumor as well as the suitability of the patient for an operation evaluating the histological type of cancer, the degree of invasion, and the patientís other medical conditions.

TUMOR RESECTABILITY

Resectability of the tumor depends on the type of cancer as well as the degree of invasion which is determined by characteristics of the primary tumor as well as the presence of lymph node or distant metastases.

Type of Cancer

If the lesion is accessible, bronchoscopy, inserting a scope to inspect the airway, can provide tissue to make a diagnosis. In addition, bronchial washing, brushing, and transbronchial needle aspiration can aid in establishing the diagnosis. In lesions that cannot be seen, bronchoalveolar lavage, washing the airways with saline, can provide cells to be examined by a cytopathologist. An alternative approach, especially for peripheral lesions, is the use of percutaneous computed tomography (CT)-guided needle biopsy. Possible complications include pneumothorax, the leakage of air between the lung and the chest wall, which is treated conservatively in the majority of cases. If present, pleural fluid, surrounding the lung, can be sampled for cancer cells, or a biopsy of the pleura, the lining surrounding the lung, can be performed. When other studies are non-diagnostic, video-assisted thoracoscopy (VATS), a minimally invasive surgical technique inserting a scope in the space between the lung and the chest wall, is successful in making the diagnosis in 90% of cases due to the ability to visualize suspicious areas for biopsy (Figure 1) (1).



Figure 1. Video-assisted thoracoscopic wedge resection of a lung nodule.


For small cell lung cancer, chemotherapy and radiation are generally the main treatment modalities since the majority of patients have metastatic disease at the time of presentation. Surgery can be offered for limited T1 or T2 (Table 1) lesions without lymph node involvement (Stage I) followed by chemotherapy although less than 5% of patients present at this stage (2).




Patients with mixed small and non-small cell histology may also benefit from resection after chemotherapy. However, before surgery is considered, patients should undergo complete staging with CT (including the head), positron emission tomography (PET), and mediastinoscopy, placing a scope through a neck incision to examine the lymph nodes between the lungs, if needed. Non-small cell lung cancer (NSCLC), including squamous cell, adenocarcinoma, bronchoalveolar, and large cell carcinoma, is generally more amenable to resection and is present in 80% of the cases of lung cancer in North America (3).

Degree of Invasion

The optimal treatment and prognosis of NSCLC is related to the pathologic stage at presentation which is determined using the TNM system (Table 1) evaluating characteristics of the primary tumor

(T), whether there has been invasion of lymph nodes (N), and the presence of distant metastases (M). The true stage of the tumor is not always obvious at the time of diagnosis and is often higher than initially thought. TNM staging of NSCLC allows the clinician to estimate a patientís overall survival. Staging has become even more important with the increasing use of preoperative chemotherapy and radiation for locoregionally advanced tumors (Stage IIIA).





In general, stage I (confined to the lung without nodal or distant metastases), II (involvement of only lymph nodes within the lung or the hilum, the area where blood vessels enter the lung, on the same side as the tumor), and IIIA (involvement of nodes in the mediastinum, the area between the lungs, on the same side as the tumor) (Table 2) are considered potentially resectable for cure with a survival following complete resection of 76%, 47%, and 26-56% (4). Stage IIIB (involvement of the mediastinal organs, between the lungs, or lymph node metastases on the side opposite from the tumor) and IV (distant metastases) are generally considered surgically incurable although a ďgray zoneĒ exists with some advocating resection of limited N2 disease (involvement of mediastinal nodes on the same side as the tumor), stage IIIB without N2 disease or with a squamous cell histology, and stage IV with a solitary brain metastasis. To be curative, all areas invaded by cancer including involved areas of the diaphragm, pericardium, chest wall, and lymph nodes must be resected.

A number of complementary approaches are useful in staging lung cancer including CT, PET, bronchoscopy, and mediastinoscopy. The selection and interpretation of imaging studies and procedures is important in determining the optimal treatment. The goal of staging studies is to identify patients who might be potential surgical candidates since early stage lung cancer is potentially curable by surgical resection. Surgery can also be used to provide local control in advanced disease.

All patients, except those with small peripheral tumors less than 2 cm and no evidence of N2 nodal disease on CT or PET, should undergo mediastinoscopy. Patients with suspected lung cancer should undergo CT of the chest and abdomen and if available, an FDG-PET (fluorodeoxy glucose positron emission tomography) to evaluate for distant metastases which occur in 50% of patients with NSCLC. Suspicious lesions are biopsied to avoid false positive results. Patients with neurological symptoms should undergo a head CT or MRI to evaluate for metastases. A bone scan may also be useful if metastases are suspected after a thorough history and physical examination and evaluation of laboratory studies such as alkaline phosphatase and calcium. If the clinical evaluation is negative, the likelihood of finding metastases appears to be low.

Chest X-ray

The standard chest x-ray is useful in detecting the primary tumor and demonstrating its size and location but is not sensitive (the likelihood that a test will be positive in patients who have the disease) in detecting lymph node involvement. Chest x-ray may show a pleural effusion, destruction of ribs or vertebrae, and involvement of the phrenic nerve with elevation of the hemidiaphragm. Chest x-ray is inferior to CT in evaluating mediastinal nodal disease. If suspected mediastinal involvement on x-ray is found, more accurate imaging studies should be obtained.

Computed Tomography (CT)

CT localizes the primary tumor and allows characterization of its size and relationship to adjacent structures as well as involvement of hilar and mediastinal lymph nodes, with those larger than 1 cm considered abnormal. Contrast-enhanced helical CT of the chest and abdomen are routinely performed to evaluate for metastases to the liver and adrenal glands. Nonresectable lesions include those involving the carina (the junction of the right and left mainstem bronchi) and tumors surrounding the aorta, the main portions of the pulmonary arteries, or more than 180 degrees of the esophagus. CT is useful in guiding further biopsies using mediastinoscopy or VATS. However, CT is only 57% sensitive and 82% specific (the likelihood that a test will be negative in patients who do not have the disease) for detecting positive mediastinal nodes (5), and inflammation can lead to under or over-staging. In addition, nodal metastases can be present in 21% of nodes less than 1 cm in size (3). Magnetic resonance imaging (MRI) has a similar sensitivity and specificity to CT but does not require contrast. However, spatial resolution is inferior to CT, and the images are limited by cardiac and respiratory motion artifacts.

Bronchoscopy

Bronchoscopy can be used to define the proximal extent of the tumor. Bronchoscopic signs that a lesion is not resectable include vocal cord paralysis suggesting nerve invasion and tumor involving the carina or trachea. Lymph node invasion can be evaluated using transbronchial needle aspiration by passing a needle through the bronchoscope and the bronchial wall into the lymph node. However, sensitivity is only 50% with a 96% specificity (3).

Mediastinoscopy

When radiologic studies are inconclusive or enlarged mediastinal lymph nodes greater than 1 cm are present, surgical techniques including cervical mediastinoscopy (Figure 2), anterior mediastinotomy (through a small anterior chest incision), and thoracoscopy are used to evaluate lymph node involvement.



Figure 2. Illustration demonstrating cervical mediastinoscopy
to evaluate lymph node involvement by lung cancer


Mediastinoscopy is the gold standard for mediastinal staging with an 89% sensitivity and 100% specificity for non-small cell lung cancer. Only 8% of patients with a negative mediastinoscopy were found to have mediastinal nodal disease at exploration (6). The sensitivity may be improved in the future by using techniques that can better identify microscopic disease, such as molecular methods to detect the presence of tumor RNA or proteins. Cervical mediastinoscopy can be performed as an outpatient procedure with minimal complications. Anterior mediastinotomy or VATS can be used to evaluate lymph nodes that are less accessible by mediastinoscopy, particularly nodes in the left chest. VATS (Figure 3) can also be used to exclude a malignant pleural effusion in patients who would otherwise be candidates for complete surgical resection.



Figure 3. Pleural nodule discovered during video-assisted thoracic surgery.


Positron Emission Tomography

Positron emission tomography (PET) takes advantage of the high glucose metabolism of tumor cells. As demonstrated in figures 4 and 5 below, tumors can be easily identified. Figure 4 shows a tumor in the right upper lobe as a bright yellow spot. In addition, there is a second bright yellow spot in the lung as indicated by the arrow. This tells the surgeon that the tumor has likely spread to this region. The sensitiviy for the detection of lung cancer has been reported to be in the 95% range (7,12,13). Some benign processes, including several types of infectious lesions can simulate cancer with this test. For this reason, biopsy is required to confirm the diagnosis. PET scanning can also be used to find spread of disease outside of the chest. Figure 5 shows a CT with Fusion PET image of the upper abdomen on the same patient as in figure 4. Notice that the adrenal gland (arrow) appears as a bright yellow spot on the FUSION image. This implies the disease has spread outside the chest. This finding would alter the management in this patient. The technique of "FUSING" CT with PET images has greatly enhanced the ability of doctors to detect and characterize the extent of disease.



Figure 4. Scan of a lung cancer patient with a nodule in the right upper lobe. The PET scan is on the left. The picture on the right is a FUSION image of the PET and CT scan. Notice the bright yellow spot in the right upper lobe (arrow) and the 2nd spot in the hilum (arrow head). This information tells the surgeon that the disease has likely spread to this region.




Figure 5. CT with Fusion PET image on same patient. Notice that the adrenal gland (arrow) appears as a bright yellow spot on the FUSION image. This implies the disease has spread outside the chest.


By identifying unexpected distant metastases in 10-20% of patients (5), PET helps to avoid a nontherapeutic operation. PET is also attractive since the whole body can be imaged in one session. FDG-PET has been reported to be 100% sensitive for adrenal metastases (5) although PET is not accurate in identifying brain metastases due to normal uptake of FDG by the brain. In addition, metabolism may be altered by infection leading to false results in areas where histoplasmosis or granulomatous disease are common. Current recommendations require confirmation of all PET-positive mediastinal nodes with mediastinoscopy. PET is also useful in guiding mediastinal biopsy, especially when disease is identified in a nodal region not accessible by mediastinoscopy alone. Whether negative studies should be followed by mediastinoscopy is controversial and depends on surgeon preference and the institutional experience.

PET scanning provides functional information and has been found to be useful for determining the diagnosis, stage, and prognosis of lung cancer. Several studies have shown that PET is more accurate than CT for staging mediastinal lymph nodes (7). This powerful new tool is revolutionizing the way surgeons care for lung cancer patients. More accurate staging also helps the Oncologists and Radiation Therapists to plan the most appropriate treatment for patients who have inoperable disease.

PATIENT SUITABILITY

The incidence of complications after lung resection is 2-5% for otherwise healthy patients and increases up to 50% in those with lung disease (3). The majority of patients with lung cancer are older and have a history of smoking with chronic obstructive pulmonary or heart disease. Patients with cardiac symptoms should undergo further evaluation such as stress testing. While the surgical mortality ranges from 4-12%, cardiac and pulmonary complications occur in up to 30% of patients (8). Once a patient is determined to be a candidate for curative resection by appropriate staging, the patientís functional capacity is evaluated to predict the possibility of perioperative complications, long-term respiratory failure, or death. Factors such as the extent of proposed resection, preoperative lung function, and other medical problems are considered. Age by itself is not a major risk factor (3).

Pulmonary Function

While healthy adults have a large pulmonary reserve, most patients with lung cancer have decreased lung function due to a history of smoking. One of the goals of preoperative evaluation is to avoid severe postoperative respiratory insufficiency after lung resection while identifying the maximum number of patients who would tolerate pulmonary resection since it remains the only curative therapy available. All patients undergoing lung resection should have pulmonary function testing. The forced expiratory volume in one second (FEV1) and the predicted postoperative FEV1 are the parameters most commonly used and have the highest predictive value with lower volumes associated with an increased risk. Pulmonary function tests are sensitive, but not specific, and are useful in either approving patients for resection or identifying high-risk patients that require further evaluation.

Prior to performing lung resection in high-risk patients, it is crucial to determine the function of the remaining lung using tests such as quantitative ventilation and perfusion testing. After an intravenous injection and inhalation of technetium-labeled particles, the percentage of radioactivity distributed to each lung correlates with its contribution to lung function allowing a prediction of post-resection function. Resection of poorly functional lung may have relatively little effect on postoperative function. The predicted postoperative FEV1 has been correlated with the occurrence of postoperative respiratory complications. Exercise testing, including stair climbing, treadmill tests, and bicycle ergometry, is also useful and stresses the entire cardiopulmonary system of oxygen delivery. Measuring the maximum oxygen uptake during exercise testing may also be useful in predicting postoperative complication rates, particularly for patients with other testing indicating limited pulmonary reserve. . Proper patient selection using such techniques has been correlated with decreases in complication rates, time on mechanical ventilation, and length of hospital stay (9).

We have adopted an algorithm for the preoperative functional assessment for lung resection shown in Figure 6. However, due to the poor prognosis of NSCLC managed non-operatively, all patients should be considered for resection, and the final decision on whether to proceed depends on multiple factors with each patient considered individually.



Figure 6. Algorithm outlinkint the preoperative functional evaluation for lung
cancer resection. (FEV1, forced expiratory volume in one second; ppo, predicted postoperive: VO2Max, oxygen uptake)


Risk Factor Modification

Potentially modifiable risk factors include symptomatic obstructive airway disease, smoking, obesity, and malnutrition. Aggressive pre- and perioperative management can decrease pulmonary complications by 50%. Long-term smoking is the most important risk factor for lung carcinoma, and a smoking history greater than 20 pack years significantly increases the surgical risks (10). Smoking cessation more than eight weeks prior to coronary artery bypass decreased the risk of pulmonary complications to that of nonsmokers (11). Preoperative teaching, optimization of medications for obstructive pulmonary disease, and an exercise program may also be important in minimizing postoperative complications.

CONCLUSIONS

Lung cancer is the leading cause of death due to cancer in the United States. While the majority of the patients have advanced disease at the time of presentation, complete surgical resection remains the best hope for cure for non-small cell lung carcinoma. After determining that lung cancer is present, a number of complementary approaches are used to determine the histological type of cancer, the degree of invasion, and the patientís cardiac and pulmonary reserve. Patients with limited disease and adequate physiologic reserve should undergo lung cancer resection.


Corresponding author: Andrew Chang, Department of Surgery, University of Michigan Medical Center, 2120 Taubman Center, 1500 E. Medical Center Drive, Box 0344, Ann Arbor, Michigan 48109, Phone: (734) 763-7418, Fax: (734) 615-2656, E-mail: andrwchg@umich.edu


Author Information

1 General Surgery Resident, Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan 48109
2 Clinical Associate Professor, Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan 48109
3 Assistant Professor, Department of Surgery, Section of Thoracic Surgery, University of Michigan Medical Center, Ann Arbor, Michigan 48109

3 Corresponding author: Andrew Chang, Department of Surgery, University of Michigan Medical Center, 2120 Taubman Center, 1500 E. Medical Center Drive, Box 0344, Ann Arbor, Michigan 48109, Phone: (734) 763-7418, Fax: (734) 615-2656, E-mail: andrwchg@umich.eduLung Cancer: Selecting Patients for Surgical Resection 


 


Additional Authors:  

Works Cited:  
  1. Landreneau, R. J., Mack, M. J., Dowling, R. D., Luketich, J. D., Keenan, R. J., Ferson, P. F., and Hazelrigg, S. R. The role of thoracoscopy in lung cancer management. Chest, 113: 6S-12S, 1998.
2. Leo, F. and Pastorino, U. Surgery in small-cell lung carcinoma. Where is the rationale? Semin Surg Oncol, 21: 176-181, 2003.
3. Leonard, C. T., Whyte, R. I., and Lillington, G. A. Primary non-small-cell lung cancer: determining the suitability of the patient and tumor for resection. Curr Opin Pulm Med, 6: 391-395, 2000.
4. Martini, N., Bains, M. S., Burt, M. E., Zakowski, M. F., McCormack, P., Rusch, V. W., and Ginsberg, R. J. Incidence of local recurrence and second primary tumors in resected stage I lung cancer. J Thorac Cardiovasc Surg, 109: 120-129, 1995.
5. Reed, C. E., Harpole, D. H., Posther, K. E., Woolson, S. L., Downey, R. J., Meyers, B. F., Heelan, R. T., MacApinlac, H. A., Jung, S. H., Silvestri, G. A., Siegel, B. A., and Rusch, V. W. Results of the American College of Surgeons Oncology Group Z0050 trial: the utility of positron emission tomography in staging potentially operable non-small cell lung cancer. J Thorac Cardiovasc Surg, 126: 1943-1951, 2003.
6. Passlick, B. Initial surgical staging of lung cancer. Lung Cancer, 42 Suppl 1: S21-25, 2003.
7. Mac Manus, M. P. and Hicks, R. J. PET scanning in lung cancer: current status and future directions. Semin Surg Oncol, 21: 149-155, 2003.
8. Romano, P. S. and Mark, D. H. Patient and hospital characteristics related to in-hospital mortality after lung cancer resection. Chest, 101: 1332-1337, 1992.
9. Olsen, G. N., Bolton, J. W., Weiman, D. S., and Hornung, C. A. Stair climbing as an exercise test to predict the postoperative complications of lung resection. Two years' experience. Chest, 99: 587-590, 1991.
10. Liptay, M. J. and Fry, W. A. Complications from induction regimens for thoracic malignancies. Perioperative considerations. Chest Surg Clin N Am, 9: 79-95, 1999.
11. Warner, M. A., Divertie, M. B., and Tinker, J. H. Preoperative cessation of smoking and pulmonary complications in coronary artery bypass patients. Anesthesiology, 60: 380-383, 1984.
12. Marom, E. M, Sarah, S., James E. H., and Patz, E.F. Jr
T1 Lung Cancers: Sensitivity of Diagnosis with Fluorodeoxyglucose PET
Radiology 2002; 223: 453-459.
13. Gambhir, S.S., Czernin, J., Schwimmer, J., Silverman D.H.S., Coleman, E.R., and Phelps, M.E., A Tabulated Summary of the FDG PET Literature. Journal of Nuclear Medicine Vol. 42 No. 90050 1S-93S
 
 


Article Links:  
 
  • Multidisciplinary Lung Cancer Clinic: University of Michigan Comprehensive Cancer Center
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  • Lung Cancer Treatment Options
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  • Lung Cancer Book Section
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