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Communications to the Editor |

Malignant Pleural Effusion in Non-small Cell Lung Cancer—Time for a Stage Revision? FREE TO VIEW

Frank E. Mott, MD; Neeraj Sharma, MD; Pandora Ashley
Author and Funding Information

Texas A&M University Temple, TX

Correspondence to: Frank E. Mott, MD, Division of Hematology/Oncology, Scott & White Clinic, Texas A&M University, HSC, 2401 S 31st St, Temple TX, 76508



Chest. 2001;119(1):317-318. doi:10.1378/chest.119.1.317
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Published online

To the Editor:

Lung cancer is the leading cause of cancer-related death in both men and women, and non-small cell histology accounts for 80 to 85% of cases.1 The staging of non-small cell lung cancer (NSCLC) provides the opportunity to classify the anatomic extent of the disease and to determine treatment as well as to define prognoses. The staging system for NSCLC has evolved over the past 26 years in an effort to better serve these principles.

In 1974, the American Joint Committee for Cancer Staging (AJCC) formed the Task Force on Carcinoma of the Lung and issued recommendations for the staging of NSCLC.2In 1985, the AJCC combined with the Union Internationale Contre Cancer and with Japanese and German representatives to propose a revised international staging system for lung cancer.3This was further revised in 1997.4

Malignant pleural effusion was considered a T4 (stage IIIB) lesion in the 1985 revision, thus implying that patients with malignant pleural effusion had a more favorable prognosis than did patients with M1 (stage IV) disease. The 1997 revision did not alter that status. However, Naruke et al5 showed that the survival rate of patients with stage IIIB disease who have malignant effusions is considerably worse than those with stage IIIB disease who do not have malignant effusions. The 5-year survival rate for patients with stage IIIB disease who do not have effusions was 45.4% vs 15.9% for those patients who have malignant pleural effusions. Naruke et al5 also reported a 42.5% 5-year survival rate for patients with pleural effusions that were deemed nonmalignant. While these numbers seem a little high, they nonetheless reflect the fact that patients with malignant pleural effusions are prognostically similar to patients with stage IV disease.

The above data suggest a difference between malignant and nonmalignant pleural effusions associated with NSCLC. A pleural effusion is considered malignant if the findings of cytologic testing are positive or, in the event of negative results of cytologic testing, the fluid is exudative and/or bloody. In rare instances, pleural effusions will be transudative and nonbloody, will have negative results of cytologic testing, and can be considered as reactive, in which case the tumor stage would be T1–3. Sugiura et al6 compared the survival of 197 patients with stage IIIB disease, with and without pleural effusion, and stage IV disease. They found that the median survival time for patients with stage IIIB disease who had pleural effusions was comparable to that of patients with stage IV disease (7.5 and 5.5 months, respectively) and was significantly worse than that for patients with stage IIIB disease who did not have pleural effusions (median survival time, 15.3 months). Among the patients with pleural effusions, there was no difference in survival time whether the results of fluid cytology testing were positive or negative, provided the latter patients had either bloody and/or exudative fluid that was clinically judged to be the result of the underlying lung cancer.

Our experience at the Scott & White Clinic is similar. We reviewed tumor registry data for the preceding 5 years (1993 to 1998). A chart review of all patients coded as stage IIIB and IV was performed. Stage IIIB patients with clearly defined pleural effusions that were either cytologically positive or were bloody, exudative, and associated with an underlying histology-documented NSCLC were evaluated separately. There were 120 patients with stage IIIB disease who met the criteria and were considered evaluable for survival (patients without pleural effusions, 83 patients; and patients with pleural effusions, 37 patients). The median survival time for the patients without pleural effusions was 12 months (range, 1 to 74 months), while the median survival time for those patients with pleural effusions was 2 months (range, 1 to 17 months) [Fig 1 ] . One hundred ninety-two patients with stage IV disease showed a median survival time of 4 months (range, 1 to 41 months) [Fig 2 ] . While the median survival time for patients with stage IIIB disease with effusions was less than that for patients with stage IV disease, the number was small due to many patients being excluded for not meeting the criterion of malignant pleural effusion. Nonetheless, the survival time paralleled that of patients with stage IV disease and was considerably worse than that of patients without malignant pleural effusions.

Many clinicians caring for lung cancer patients often approach stage IIIB disease with pleural effusion like stage IV disease and treat the patient primarily with chemotherapy. Many ongoing clinical trials in patients with advanced lung cancer include patients with stage IIIB disease who have malignant effusions and patients with stage IV disease. Patients with stage IIIB disease without pleural effusions are often considered for combined modality therapy with chemoradiation. In a study addressing the 1997 International Staging System, Green et al7 suggested that it would be more appropriate to classify patients with malignant pleural effusions as having stage IV disease rather than stage IIIB disease.

I agree with this and would recommend changing the classification of patients with malignant pleural effusions. Those patients who have either cytologically positive fluid or fluid that is bloody and/or exudative and appears clinically associated with the underlying lung cancer should henceforth be given a distinct classification of stage IVA. This would more accurately reflect the prognosis of this group of patients with NSCLC, would streamline clinical trials, and would make treatment considerations more consistent. All patients with M1 disease would be at stage IVB. Alternatively, malignant pleural effusions could simply be included in stage IV disease.. However, the division into A and B would identify the subtle differences between these two groups, even though survival expectations are comparable. Either way, this would leave patients with T4 lesions without pleural effusion and N3 nodes in the stage IIIB group, for whom treatment with chemoradiation would be more appropriate.

Figure Jump LinkFigure 1. Kaplan-Meier survival rate by AJCC stage for patients with stage IIIB NSCLC.Grahic Jump Location

Figure Jump LinkFigure 2. Kaplan-Meier survival rate by AJCC stage for patients with stage IV NSCLC.Grahic Jump Location

References

Parker, SL, Tong, T, Bolden, S, et al (1997) Cancer statistics, 1997.CA Cancer J Clin47,5-27. [CrossRef] [PubMed]
 
Mountain, CF, Carr, DT, Anderson, WAD A System for the clinical staging of lung cancer.AJR Am J Roentgenol1974;120,130-138
 
Mountain, CF A new international staging system for lung cancer.Chest1986;89,225S-231S. [PubMed]
 
Mountain, CF Revisions in the international system for staging lung cancer.Chest1997;111,1710-1717. [CrossRef] [PubMed]
 
Naruke, T, Tsuchiya, R, Kondo, H, et al Implications of staging in lung cancer.Chest1997;112,242S-248S. [CrossRef] [PubMed]
 
Sugiura, S, Ando, Y, Minami, H, et al Prognostic value of pleural effusion in patients with non-small lung cancer.Clin Cancer Res1997;3,47-50. [PubMed]
 
Green, M, Leong, S, Caio, M, et al The 1997 International Staging System for Non-Small Cell Lung Cancer: have all the issues been addressed?Chest1999;115,242-248. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Kaplan-Meier survival rate by AJCC stage for patients with stage IIIB NSCLC.Grahic Jump Location
Figure Jump LinkFigure 2. Kaplan-Meier survival rate by AJCC stage for patients with stage IV NSCLC.Grahic Jump Location

Tables

References

Parker, SL, Tong, T, Bolden, S, et al (1997) Cancer statistics, 1997.CA Cancer J Clin47,5-27. [CrossRef] [PubMed]
 
Mountain, CF, Carr, DT, Anderson, WAD A System for the clinical staging of lung cancer.AJR Am J Roentgenol1974;120,130-138
 
Mountain, CF A new international staging system for lung cancer.Chest1986;89,225S-231S. [PubMed]
 
Mountain, CF Revisions in the international system for staging lung cancer.Chest1997;111,1710-1717. [CrossRef] [PubMed]
 
Naruke, T, Tsuchiya, R, Kondo, H, et al Implications of staging in lung cancer.Chest1997;112,242S-248S. [CrossRef] [PubMed]
 
Sugiura, S, Ando, Y, Minami, H, et al Prognostic value of pleural effusion in patients with non-small lung cancer.Clin Cancer Res1997;3,47-50. [PubMed]
 
Green, M, Leong, S, Caio, M, et al The 1997 International Staging System for Non-Small Cell Lung Cancer: have all the issues been addressed?Chest1999;115,242-248. [CrossRef] [PubMed]
 
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