Staging Strategies for Lung Cancer

Abstract

LUNG CANCER HAS BECOME PERHAPS THE MOST IMPORtant cancer in the United States. The incidence has continued to increase, and lung cancer is now the leading cause of cancer death. However, most patients with lung cancer have advanced-stage disease when they first present and are not amenable to curative treatment. For the remainder, a careful search for metastatic or locally invasive tumors must be made prior to potentially curative lung resection. The lymph node drainage system for the lungs lies primarily in the mediastinum, and because it is a compact space enclosed in a rigid, bony cage, finding small lymph nodes that contain cancer is challenging. Computed tomographic (CT) evaluation of the chest reliably identifies and characterizes lung tumors but is less useful for evaluating the mediastinum for malignant disease. Mediastinal evaluation by CT is only 51% sensitive (95% confidence interval [CI], 47%-54%) and 85% specific (95% CI, 84%-88%) for establishing the diagnosis of lymph node disease in lung cancer. Consequently, mediastinoscopy is a required intermediary step between an otherwise negative metastatic evaluation for lung cancer and definitive pulmonary resection. Although complications are infrequent, mediastinoscopy is an operative procedure requiring general anesthesia and can substantially add to the overall morbidity and cost of lung cancer treatment. Positron emission tomographic (PET) scanning with the glucose analog fluorodeoxyglucose offered great promise for imaging tumors. Because cancers have higher-thannormal glucose uptake coupled with lower phosphorylation rates, fluorodeoxyglucose preferentially accumulates in malignant cells. Early studies showed great promise for this noninvasive radionucleide scanning technique to identify malignant cells too small to detect by CT. Nevertheless, inflammatory nodes resulting in false-positive results and lymph nodes too small for the resolution of current PET scanners result in a disappointingly low sensitivity of 74% (95% CI, 69%-79%) and specificity of 85% (95% CI, 82%-88%). Current clinical practice guidelines recommend that patients with lung cancer undergo CT scanning with the intent of identifying lymph node metastases and, if this imaging evaluation is unrevealing, that they next undergo PET scanning. With this strategy, some patients will still have metastatic disease in the mediastinum after noninvasive imaging. Currently, these patients undergo mediastinoscopy prior to thoracotomy in an effort to reduce the rate of unnecessary chest explorations that are potentially aborted because of previously unrecognized unresectable or metastatic lung cancer. In recent years, advances in endoluminal ultrasound (EUS) technologies facilitated high-resolution imaging of structures adjacent to the esophagus and bronchus. These devices enable biopsy of suspicious mediastinal lesions with the promise of replacing or eliminating PET imaging and mediastinoscopy in the evaluation of patients with lung cancer. Indeed, the combination of EUS and endobronchial ultrasound (EBUS) with fine-needle aspiration in nonrandomized trials demonstrated a 93% sensitivity (95% CI, 81%-99%) and 97% specificity (95% CI, 91%-99%) for establishing the presence of mediastinal disease in lung cancer patients. These impressive results suggest that the combination of EUS and EBUS could replace mediastinoscopy as well as avoid thoracotomies that proved unnecessary because of the incidental finding of advanced-stage disease. In this issue of JAMA, Annema and colleagues report the results of a randomized trial comparing mediastinoscopy and endosonography for mediastinal nodal staging of lung cancer. This study highlights several important issues regarding the importance of properly staging lung cancer preoperatively to avoid surgical intervention in a group of patients who have no proven benefit from resection and in fact would have a reduction in their quality of life from an unnecessary thoracotomy. This randomized study compares the use of endoscopic ultrasound via either esophagoscopy, bronchoscopy, or both, followed by surgical staging if no nodal metastases were found, to the past gold standard of surgical staging either by mediastinoscopy or parasternal biopsy. This welldesigned study attempts to answer the question of how this