JACKSONVILLE, Fla. - Using two different endoscopes together is better than using one to stage lung cancer, and is also much more precise and less invasive than the surgical method now most commonly used, researchers at Mayo Clinic in Jacksonville, Fla., report in the Feb. 6 issue of the Journal of the American Medical Association.
This new technique, which uses two small flexible tubes, one of which is inserted into a patient's esophagus to access lymph nodes in the back of the lungs while the other is placed into the trachea, or airway, to reach nodes at the front and sides, was 93 percent accurate in finding malignant lymph nodes in a group of 138 patients. This is substantially more precise than all other lung cancer staging methods now in use today, say the researchers, who tested three different methods of non-invasive staging in their study.
"Both scopes together found more malignant lymph nodes than did the use of a single endoscope," says the study's lead investigator, Michael Wallace, M.D., M.P.H., Professor of Medicine at Mayo Clinic, Jacksonville, Fla. "Doing both procedures at once takes little time, requires only a mild sedative, and patients go home the same day."
The combination technique was pioneered by Wallace, a gastroenterologist, and study co-author Jorge Pascual, M.D., a pulmonologist. Since the researchers have seen how effective this method is, the two tests are now used routinely at Mayo Clinic Jacksonville to stage lung cancer patients. The researchers are among the first to publish studies examining use of the two scopes, and this study is the largest and most comprehensive to date.
Lung cancer is the most common cause of cancer death. Treatment of the disease depends on whether the cancer has spread outside the lungs, and in order to know that, physicians need to biopsy (remove a small piece of tissue for examination) the lymph nodes that are adjacent to the organ. Patients whose cancer has not spread can be treated with potentially curative surgery to remove lung tumors, and chemotherapy and radiation are used for patients whose cancer has spread. Staging of cancer is the process by which doctors determine whether a cancer has spread to other sites such as lymph nodes or other organs, and thus which is the most appropriate treatment.
Shortcomings in each method of staging
The traditional staging technique is to first perform a CAT scan of the lungs to find enlarged lymph nodes. PET scans are also used to determine if a cancer has spread, but both CT and PET have limits, Dr. Wallace says. They can only determine if a lymph node is enlarged or has a high metabolism; features which suggest, but do not prove that cancer is present. Most doctors, including the American College of Chest Physicians, now recommend that CT and PET scans be confirmed with a biopsy of the lymph nodes.
Traditionally, such a biopsy could only be done surgically by inserting a rigid steel scope into the chest through a surgical opening above the breast bone. The scope is maneuvered to lymph nodes of interest and a small piece of tissue is taken to look for signs of cancer. This procedure, known as a mediastinoscopy, can only access lymph nodes on the front or sides of the lungs, Dr. Wallace says. Studies summarized by the American College of Chest Physicians have shown it is approximately 78 percent sensitive - that is, of all patients whose lung cancer has spread to lymph nodes, this technique can pick up, at most, 78 percent of them, he says. Another limitation of mediastinoscopy is the need for general anesthesia, and the small but real risk of major complications, Dr. Wallace says.
Most lung cancer staging still is done today by mediastinoscopy, but several less-invasive techniques are also now being used. The most common is transbronchial needle aspiration (TBNA), in which a physician places a bronchoscope into the trachea and based on a CT scan, passes a small needle through the trachea into where a suspicious lymph node is believed to be. "You can't directly see the lymph nodes, which significantly limits accuracy of TBNA," he says.
In the mid-1990s, another non-invasive method of scoping known as endoscopic ultrasound (EUS) was used to stage lung cancer. This scope, which uses a flexible tube with an ultrasound probe, has long been used to look for and sample tumors in the gastrointestinal tract. Dr. Wallace and others adapted it for use in lung cancer staging because they realized the probe, in the esophagus, could provide a clear image of the lymph nodes behind the lungs. In this procedure, physicians guide a very small needle into the lymph node to take a biopsy (a procedure called fine needle aspiration). But while extremely safe and accurate for lymph nodes in the back of the chest, the EUS scope could not biopsy lymph nodes in the front of the chest.
Four years ago, a new type of staging probe was developed that is a smaller version of EUS and is used in the airway. This one, the endobronchial ultrasound probe (EBUS), can view the front and sides of the lungs. Based on the complementary nature of the two procedures, Mayo Clinic researchers began testing in 2005 the use of both instruments together in the belief that patients would benefit from a comprehensive view of the lymph nodes surrounding their lungs.
To find out which of the scoping methods was most beneficial, 138 patients with lung cancer agreed to be tested with three methods: TBNA, EUS, and EBUS. These procedures were all performed in one session in which a patient was lightly sedated. TBNA and EBUS were performed first by one or two pulmonologists (lung specialists), who then left the procedure room, and then gastroenterologists (who had expertise in endoscopy via the esophagus) performed the EUS. The study was performed using the most rigorous "double blind" method so that each doctor evaluated each test without knowledge of the other test results. After all procedures were complete, the results were evaluated by a surgeon, and surgery performed only if there was no evidence of cancer spread.
In all, 42 malignant lymph nodes were found in the patients. The researchers then looked at the results of the tests both individually and in combination. The combination of EUS and EBUS detected 93 percent of 42 malignant lymph nodes. The three remaining malignant nodes were found during surgery. Wallace said. "One was next to the aorta, the body's main artery, so it was unsafe to biopsy, and the other two were very small cancers missed by the needle sampling," he says.
"The combination of EUS and EBUS allows for a near complete medical staging for patients with suspected lung cancer," Dr. Wallace says.
Estimated sensitivities for the other procedures were: EUS (69 percent); EBUS (69 percent), TBNA (36 percent), EUS and TBNA (79 percent); and EBUS and TBNA (76 percent).
Although Mayo Clinic Jacksonville routinely uses the EUS-EBUS combination to stage lung cancer, Dr. Wallace says not that many physicians have been trained in these techniques to date, and that their use requires "good integration between all of the different specialties involved in the care of lung cancer patients."
The study was funded by the National Cancer Institute, and the James and Esther King Foundation of the State of Florida, Department of Health. Grant support in the form of equipment was provided by the Olympus Corporation, makers of the endoscopes (bronchoscope, EUS, and EBUS). Other study authors are Massimo Raimondo, M.D., Timothy Woodward, M.D., Barbara McComb, M.D., Julia Crook, Ph.D., Margaret Johnson, M.D., Mohammad Al-Haddad, M.D., Seth Gross, M.D., Surakit Pungpapong, M.D., Joy Hardee, CCRA, and John Odell, M.D.