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Ann Thorac Surg 1999;68:1039-1042
© 1999 The Society of Thoracic Surgeons
a Division of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan
b Department of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan
Address reprint requests to Dr Nishiwaki, Division of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan
e-mail: ynishiwa{at}east.ncc.go.jp
Abstract
Background. In the official guidelines published recently, radiographic staging procedures were not recommended for patients who have non-small-cell lung cancer with negative clinical evaluation.
Methods. We did a retrospective analysis of 755 patients with non-small-cell lung cancer in clinical stage T1–2 N0 between 1982 and 1996. The patients all had a full series of imaging procedures, based on the staging protocol. Their medical records were reviewed with respect to how often distant metastasis was detected by these procedures and whether the patients showed any symptoms and laboratory abnormalities indicating extrathoracic metastasis.
Results. The incidence of distant metastasis detected by the imaging procedures was 2.1% (nine of 419) in T1 N0 cases and 5.4% (18 of 335) in T2 N0 cases. Silent metastasis was found only in 0.5% (2 of 419) of the T1 N0 cases and 0.9% (3 of 335) of the T2 N0 cases. The cost of these staging procedures was approximately one million dollars.
Conclusions. Considering the cost and time savings, staging procedures are not warranted for patients with non-small-cell lung cancer stage T1–2 N0 with negative clinical evaluations.
Clinical staging in non-small-cell lung cancer (NSCLC) is essential to determine the prognosis and appropriate treatment [1]. It has been controversial whether all staging studies should be done routinely for NSCLC patients in apparently early stage disease with no evidence of distant metastasis [1–11]. Most studies failed to show benefit of the staging procedures because of low specificity, low sensitivity, and high cost [3, 4, 8, 11]. Moreover, negative results of the procedures failed to predict the low incidence of early distant recurrence [8]. However, some investigators advocated routine investigation by improving the accuracy of available procedures [7, 9, 10]. Metaanalyses published recently [12, 13] indicated that the likelihood of finding metastatic disease by subsequent staging test was low, when comprehensive clinical evaluation was negative, although there was great variation in the methodology of individual studies. In our hospital, as in many other institutes in Japan, a full-series staging protocol was adopted for all NSCLC cases, including radiographic staging procedures, chest computed tomography (CT), radioisotope bone scanning, enhanced magnetic resonance imaging or CT of the brain, and abdominal enhanced CT or ultrasonography. We retrospectively analyzed a large number of results of imaging procedures and follow-up data. The purposes of this study were to clarify (1) how often extrathoracic metastasis was detected by staging procedures in patients limited to clinical stage T1–2 N0, (2) how many of these upstaged patients had clinical symptoms or laboratory abnormalities suggestive of distant metastasis, and (3) whether it is beneficial to perform all staging procedures for all of them routinely, by performing a cost analysis.
Patients and methods
We analyzed records of all patients with a histologic diagnosis of lung cancer, referred to the National Cancer Center Hospital East and the National Matsudo Hospital (former institute of the National Cancer Center Hospital East) between January 1982 and May 1996. The staging protocol during this period consisted of enhanced chest CT, radioisotope bone scanning, enhanced MRI or CT of the brain, and abdominal enhanced CT or ultrasonography.
Eight hundred three patients had NSCLC in clinical stage T1–2 N0. Clinical stage N0 was defined as neither mediastinal nor hilar lymph node with a diameter greater than 1.0 cm in nonsquamous cases and greater than 1.5 cm in squamous cell carcinoma cases as detected on enhanced chest CT. Forty-nine patients were excluded, because they had apparent metastasis in the peripheral lymph nodes, in the opposite lung on chest CT, or both. The remaining 754 patients were examined as to whether they showed any clinical findings of distant metastasis. The findings suggestive of M1 disease were defined, according to the literature [7, 8], as follows: (1) history: pain, body weight loss greater than 10%, and neurologic symptoms including headaches, nausea, and seizures; (2) physical examination: hepatomegaly, bone tenderness, and neurologic abnormalities found by neurologic examination; and (3) laboratory data: elevation of alkaline phosphatase, calcium, aspartate aminotransferase, lactate dehydrogenase, or total bilirubin.
Cost analysis was done using the Japanese data as of September 1998. Cost was converted to US dollars in March 1999 (1 US dollar = 120 yen).
The patient characteristics are shown in Table 1. Adenocarcinoma was the most common histology, followed by squamous cell carcinoma. Most patients had good performance status. Before the staging procedures, 419 cases were classified as clinical T1 N0 Mx, and 335 as T2 N0 Mx.
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Of the 419 clinical T1 N0 cases, nine (2.1%) extrathoracic metastases were detected by radiographic staging procedures (Table 2). Seven of nine had clinical findings of distant metastasis. Of the 335 clinical T2 N0 cases, 20 distant metastatic sites in 18 patients (5.4%) were detected. Fifteen of the 18 patients had the clinical findings. All these metastases detected by the imaging procedures were confirmed as true positive by following their clinical courses.
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Cost analysis is shown in Table 4. Using staging procedures, only 5 patients with silent metastases were spared an unnecessary thoracotomy, a cost savings of $50,000. The total cost of staging was $974,168.
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This large volume retrospective study determined the frequency of detection of extrathoracic metastasis in NSCLC patients with clinical stage T1–2 N0, and the incidence of clinical and laboratory abnormalities suggestive of distant metastasis in this population.
Our results showed that even if a tumor does not seem to invade any lymph nodes on chest CT, distant metastasis can be detected by full staging procedures. However, the imaging procedures could provide accurate staging in only a few cases, 0.5% (2 of 419) in T1 N0 cases and 0.9% (3 of 335) in T2N0 cases with silent metastasis. The rate of silent metastasis might actually be lower, because this study could have underestimated the physical findings because of the limited information gathered retrospectively from medical records. Complete history taking and physical examination focusing on detection of distant metastasis would decrease the number of asymptomatic cases. It was reported that patients with adenocarcinoma or large cell carcinoma were at a significantly higher risk for extrathoracic metastases compared with patients with squamous cell carcinoma [7]. However, there was no difference between pathology in the patients reviewed in this study.
Omitting the staging procedures could result in the following advantages. First, an enormous cost can be saved. Although this cost analysis was crude, it showed that approximately $1 million was spent to detect only 5 patients whose thoracotomy was unnecessary, a cost savings of $50,000. The benefits of the procedures, ie, prolonged life by adequate treatment, should be balanced against the cost of the procedures. However, the early detection of metastasis has not been found to affect the survival [8]. Cost-effectiveness can be achieved only when more effective treatment for metastasis and better accuracy of the imaging procedures are developed. Second, time can be saved. According to a study on psychooncology, the period before treatment is the most stressful time for cancer patients [14], and illness uncertainty is thought to be one of the complex cognitive stressors [15]. Although the psychooncologic aspects of staging are not well studied, it might be beneficial to shorten the period before appropriate treatment is determined, not only in consideration of tumor growth but also for psychooncologic reasons. Third, inadequate treatments can be avoided in a few cases. Imaging procedures yield more or less unavoidable false-positive results, which can mislead physicians regarding appropriate treatment and lost chances for cure. Although there were no false-positive results in this study, there is a higher false-positive rate in asymptomatic patients than in symptomatic patients [11, 16, 17] supporting the position of omitting the full staging procedures.
Our study does not support routine staging procedures for NSCLC patients with clinical T1–2 N0 disease and confirms the recommendation by American Thoracic Society and European Respiratory Society [18]. Future studies should include the following points: (1) the incidence of silent metastasis in patients with clinical stage IIIA disease, who, in the future, could be offered surgical resection after preoperative adjuvant treatments; and (2) the clinical benefit of positron emission tomography with regard to determining N factors.
Although clinical T1–2 N0 patients might have distant metastasis, most of them had clinical findings of extrathoracic metastasis and only a few had silent metastasis. Considering the cost and time savings, we do not recommended full staging procedures for the NSCLC patients in clinical stages T1–2 N0 Mx when they do not show any symptoms or physical or laboratory abnormalities indicative of distant metastasis.
Acknowledgments
This study was supported in part by a Grant-in-Aid for Cancer Research (8S-1, 9-18, 9-29) from the Japanese Ministry of Health and Welfare.
References
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