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How To Prevent Lung Cancer

By far the most common indication for bronchoscopy is diagnostic. Within this category, the most common patient is someone with clinical or radiologic signs possibly caused by cancer. The bronchoscopist frequently has to answer the question of whether a suspicious lesion in the central airways or more peripheral parts of the lung is benign or malignant, primary lung cancer or metastatic spread from another malignancy. As such, this diagnostic procedure is initially especially intended for obtaining tissue for histologie investigation or material for cytology. Very often, the bronchoscopic procedure used in these patients is the simplest method for tissue procurement with little morbidity and almost neglectable mortality compared to other approaches for obtaining material from the suspicious lesion or assumed metastases. Besides being important in tissue procurement, it also has an important role as part of the procedure for the clinical staging of a lesion with proof of its malignancy, as well as in staging of lesions of unknown histology that are assumed to be malignant by other means. Examples of this are uptake of 18-fluoro-deoxy-glueose during PET or CT scan with a pattern of lobulation and spiculae, as is frequently seen in primary malignant tumors of the lung.

The bronchoscopist sees the proximal extension and can demonstrate it by biopsies of the mucosa where the resection margin during subsequent surgery will probably be free of tumor, but he can also obtain material by transbronchial needle aspiration (TBNA) of areas with N2 or N3 lymph nodes. If these TBNAs demonstrate metastatic spread to the lymph nodes, it might spare the patient a staging mediastinoscopy.

Regarding the size of the lungs and the relatively small area that can be inspected by the fiberoptic or video bronchoscope, it is a remarkable successful procedure in the diagnostic workup of lung cancer. The majority of patients with lung cancer who are referred to the surgeon for lobectomy or pneumonectomy has pathologic proof of malignancy. However, there is still a substantial number of patients in whom it is difficult to come to a certain diagnosis by bronchoscopy. These patients may need to undergo additional invasive procedures ranging from transthoracic needle aspiration to mediastinoscopy. Finally, there remains a number of patients without proof of malignancy who have to be referred for thoracotomy, which then, in the most favourable situation, is diagnostic as well as therapeutic.

During a standard flexible bronchoscopy procedure, the bronchoscopist has several possibilities for obtaining material from a suspicious lesion, such as biopsy, brushing, washing, and TBNA. For endoscopically visible lesions, the easiest and most successful technique is taking biopsy specimens of the suspicious area under visual control with a minimum of five biopsy specimens recommended. Especially in submucosal tumors that are covered by normal mucosa without signs of tumor, it might take a few biopsies before it becomes possible to obtain material from the submucosal lesion. Whether brushes and/or washings have additional value in this situation is unclear. Another problem is the necrotic debris often found on top of a malignant lesion. Several biopsies might be needed to obtain viable tumor tissue. In a number of patients with this problem, rigid bronchoscopy enables the bronchoscopist to take larger biopsy samples, thus overcoming the covering layers of still normal mucosa or necrotic debris. For non-visible lesions, taking a biopsy or brush specimen under visual control is almost impossible. Adding fluoroscopy improves this, especially in very experienced hands, but still biopsy and brush samples from several peripheral lesions may be negative. In these situations, one might expect additional value from washing of the part of the lung with the suspicious lesion in it. In the study by van der Drift and coworkers in this issue of CHEST (see page 394), the authors performed a prospective study in a large number of patients with what, in retrospect, were all proven, malignant tumors in the lung. In all patients, biopsy, brushing, and washings were performed, and the effectiveness of washing before and after biopsy and brushing was determined. Furthermore, the authors performed a detailed cost analysis of the different procedures, and calculated the costs of all kinds of combinations and scenarios with washings and brushings as the variable. Within this cost analysis, they took into account the costs of additional diagnostic procedures if bronchoscopy, using all possible ways of tissue procurement, failed to come to a final diagnosis. The following conclusions of this study are of value for the daily practice: when a washing is done is not important, just do it; and perform all techniques for obtaining material for the pathologist but work cost-effectively and ask him to investigate brushings and washings if the biopsy specimen is not diagnostic. Despite these extensive sampling procedures, the diagnostic yield in invisible tumors is still slightly > 50%. This indicates that other approaches have to be investigated to prevent unnecessary expensive additional investigations.

For the near future, there are several ways to improve the diagnostic yield of bronchoscopy, such as the use of endobronchial ultrasound (1) and the guided biopsy and brushing during real bronchoscopy within an electromagnetic field that is performed while visualizing the bronchial tree by virtual bronchoscopy and navigating the catheter within the electromagnetic field through the branching bronchial tree toward the suspicious lesion. (2) With both of these new approaches, the specimen yield in peripheral lesions might improve. Whether they will be cost-effective in this specific situation can only be tested in a randomized clinical trial in patients with a peripheral lesion distal of the bronchoscopically visible area.

Until now, the main purpose of a diagnostic bronchoscopy was to obtain material for investigation by the pathologist. This will remain the number one priority in the workup of potentially malignant lesions; however, for the bronchoscopist another challenge is coining. The prospects of lung cancer patients have changed during the last decade. The role of the surgeon is still very important, but in only a limited number of patients (approximately 25%) will resection result in a cure. Many patients present with locoregional or even distant metastases, and for them surgery as the only treatment is useless. For these patients, other treatments are currently under investigation, and the best approach has not yet been found. Several combinations of cytotoxic drugs have been evaluated with more or less the same result. For patients outside of a trial, the standard chemotherapy regimen consists of a platinum derivative with one of the second-generation cytotoxic drugs such as the taxanes, vinorelbine, or gemcitabine. Unfortunately, not all tumors respond in the same way to the administered drugs. Some are, for instance, more sensitive to taxanes, while others respond to gemcitabine. The third generation of drugs, the biological modifiers, complicate things even more. The sensitivity to an epidermal growth factor receptor antagonist seems to be related to the presence of a mutation within the epidermal growth factor receptor gene. As treatment with second-generation and third-generation drugs is usually not cheap, and cisplatin remains a toxic treatment, unnecessary treatments should be prevented. The only way to improve this is by profiling a tumor with molecular markers, and developing tailored therapy based on the profile of the tumor. (3)

For this approach, which is more sophisticated than the currently used "trial-and-error treatment," one needs tumor cells for profiling, usually the more the better. As stated earlier, bronchoscopy is often the only technique by which material from the tumor can be taken and sent to the pathologist for histolocal or cytologic classification of the tumor. The challenge for the bronchoscopist in the near future will be how to obtain sufficient amounts of tissue, not only for diagnosis, but also, in nonsurgical cases, for profiling of the tumor. Adding washings and brushings to biopsies might also be helpful in this endeavor.

Dr. Postmus is affiliated with the Department of Pulmonary Diseases, VU University Medical Centre.

Reproduction of this 'article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml).

Correspondence to: Pieter E. Postmus MD, FCCP, Department of Pulmonary Diseases, VU Medical Center, PO Box 7057, Amsterdam 1007MB, the Netherlands; e-mail: pe.postmus@vumc.nl

REFERENCES

(1) Herth FJF, Ernst A, Becker HD. Endobronchial ultrasound guided transbronchial lung biopsy (TBBX) in solitary pulmonary nodules and peripheral lesions. Eur Respir J 2002; 20:972-975

(2) Becker HD, Herth F, Ernst A, et al. Bronchoscopic biopsy of peripheral lung lesions under electromagnetic guidance: a pilot study. J Bronchol 2005; 12:9-13

(3) Gabrielson A, Parmigiani G. Molecular profiling of lung cancer. In: Pass HI, Carbone DP, Johnson DH, et al, eds. Lung cancer: principles and practice. Philadelphia, PA: Lippincott, Williams & Wilkins, 2005; 261-269

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