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Ann Thorac Surg 2001;71:433-434
© 2001 The Society of Thoracic Surgeons
a Division of Pulmonary and Critical Care Medicine, Room 812-CSB, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC 29425, USA
e-mail: silvestri{at}musc.edu
Two scenarios continue to haunt thoracic surgeons and their patients who are candidates to undergo operation for lung cancer. In the first, a patient with lung cancer, after a thorough history, physical examination, routine laboratory work, and pulmonary function tests, undergoes surgical intervention with curative intent. Two months later, the patient is seen with headache, and brain metastases are found on computed tomography scan. Presumably, the "curative" operation would not have been done had the patient undergone additional extrathoracic staging such as head computed tomography, bone scan, and abdominal computed tomography.
In the second scenario, additional extrathoracic staging is performed "routinely" despite normal results of the clinical evaluation. One of the studies reveals an abnormality that requires further evaluation before consideration of surgical intervention. This can lead to unnecessary and invasive testing with considerable risk. Additional testing can delay operation; in one study [1], the mean time from diagnosis to thoracotomy was 109 days. Further, the waiting period between diagnosis of cancer and definitive treatment is perhaps the most psychologically stressful period of a patient’s disease course [2]. Finally, and perhaps worst of all, a patient who may benefit from curative resection may be excluded because of findings on a scan that are incorrectly interpreted as metastatic disease.
This study by the Canadian Lung Oncology Group was to have answered the question of whether or not to search for occult metastatic disease in otherwise asymptomatic patients with resectable lung cancer. To my knowledge, it is the only multicenter prospective randomized trial to address this issue. However, despite an excellent study design and implementation, the answer to the question is a "definite maybe." The primary end point of the study—thoracotomy with recurrence—occurred less often in the full investigation group, but this finding was not significant. The study results may have been negative because the sample size was too small or simply because there was no difference between groups. The authors make a good case for the former, but we can never know for sure.
To apply these results assumes that physicians performed a complete clinical evaluation. Nevertheless, there was some variation in what constituted an abnormal examination with some clinicians accepting into the study patients with mild neurologic symptoms. These patients had a higher incidence of "silent metastases." Further, what constitutes a comprehensive clinical evaluation is the subject of debate. This study chose neurologic and skeletal findings and an increased serum alkaline phosphatase value. Other studies use a much broader clinical evaluation including nonspecific findings such as weight loss, anemia, and palpable adenopathy and specific findings such as elevated calcium levels and liver function studies [3]. Using those criteria would both increase the number of presurgical staging studies (advocated in the present study) and lead to a lower rate of false-negative scans.
It would have been helpful if the authors had presented the findings of recurrence by stage because there is a correlation with metastasis incidence [4, 5]. Tanaka and associates [4] reported in 1999 that the incidence of silent metastases in stage 1 disease is exceedingly low. In their series of 754 patients, 5 (1%) had silent metastases. The incidence is reportedly higher for patients with stage IIIA disease [5].
The study by the Canadian Lung Oncology Group also showed that the staging strategy of searching for occult disease in every patient before surgical intervention in the Canadian system is cost-effective. The cost savings were achieved by avoiding futile thoracotomies. Conversely, a decision analysis [6] using Medicare data found the strategy of performing routine head computed tomography in patients without clinical evidence of metastases to be cost-ineffective. Tanaka and colleagues [4] reported similar results.
Given the complexity of diagnostic testing and the findings in this study, what recommendations can be made? A comprehensive clinical evaluation should be performed preoperatively in all patients who are being considered for thoracotomy for lung cancer. Even the subtlest of findings, whether specific or nonspecific, on clinical evaluation should prompt a search for metastatic disease. If the scan reveals an abnormality and there is any question of whether or not it represents a metastasis, tissue confirmation should be the rule.
I do not recommend a routine search for extrathoracic disease in patients with stage I disease because the incidence of metastases is low and false-positive scans occur, thus necessitating further testing. In addition, these scans appear cost-ineffective in a Medicare model and can cause unnecessary delays in operation. The weight of the evidence in this report has not changed my opinion. I do, however, recommend a routine search for metastatic disease in patients with known or suspected preoperative N2 disease before consideration for surgical intervention. Although operation is not currently recommended for that patient population, it may become part of the standard care if the current intergroup trial using neoadjuvant chemotherapy and radiotherapy plus surgical intervention has a better outcome than chemotherapy and radiotherapy alone. It makes sense that disease that has already metastasized to mediastinal lymph nodes would have a higher likelihood of silent metastasis than a peripheral T1 N0 lesion. Is my approach rooted in evidence-based origins? As in the current study, the answer is a "definite maybe." Is this controversy over? Not by a long shot. Stay tuned for clinical evaluation versus positron emission tomographic scanning.
References
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  S. G. Spiro and J. C. Porter Lung Cancer--Where Are We Today?: Current Advances in Staging and Nonsurgical Treatment Am. J. Respir. Crit. Care Med., November 1, 2002; 166(9): 1166 - 1196. [Abstract] [Full Text] [PDF]
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