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Ann Thorac Surg 2002;73:412-415
© 2002 The Society of Thoracic Surgeons

Original article: general thoracic

Malignant minor pleural effusion detected on thoracotomy for patients with non–small cell lung cancer: is tumor resection beneficial for prognosis?

Noriyoshi Sawabata, MD*a, Akihide Matsumura, MDb, Akira Motohiro, MDc, Yoshihiko Osaka, MDd, Keiichiro Gennga, MDe, Shimao Fukai, MDf, Takashi Mori, MDb for The Japan National Chest Hospital Study Group for Lung Cancer

a Division of Surgery, Toneyama National Hospital, Toyonaka, Japan
b Division of Surgery, Kinki Central National Hospital for Chest Diseases, Sakai, Japan
c Division of Surgery, South Fukuoka National Hospital, Fukuoka, Japan
d Division of Surgery, Sapporo-Minami National Hospital, Sapporo, Japan
e Division of Surgery, Okinawa National Hospital, Ginowan, Japan
f Division of Medicine, Seiranso National Hospital, Naka County, Japan

Accepted for publication October 17, 2001.

* Address reprint requests to Dr Sawabata, Division of Surgery, Toneyama National Hospital, 5-1-1 Toneyama, Toyonaka, Osaka, Japan 560-8552
e-mail: nori{at}toneyama.hosp.go.jp


   Abstract
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 Abstract
Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Background. This study attempts to clarify the benefit of surgery for non–small cell lung cancer (NSCLC) with malignant minor pleural effusion that is detected at thoracotomy.

Methods. Records of surgical patients with NSCLC were reviewed, with a definition of minor pleural effusion as less than 300 mL. The patients were divided into three groups as follows: (1) group C consisted of patients who underwent grossly complete resection; group I, patients with incomplete tumor resection; and group E, patients who underwent exploratory thoracotomy only.

Results. There were 196 patients who had minor pleural effusion; of these, 96 (46%) underwent an examination to define the malignancy status of pleural effusion after surgery. In 43 patients (45%), the effusion was found to be malignant. The median survival time and 5-year survival rate, respectively, were 13 months and 9% for group C (n = 11); 34 months and 10% for group I (n = 14; p = 0.3); and 17 months and 0% for group E (n = 18; p = 0.8).

Conclusions. Tumor resection is not beneficial for the survival of patients with NSCLC who have a minor malignant pleural effusion.


   Introduction
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 Abstract
 Introduction
Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Pleural effusion cannot always be diagnosed before thoracotomy. Sometimes non–small cell lung cancer (NSCLC) with malignant minor pleural effusion is operated on, as there is no grossly detectable remaining tumor in cases without pleural dissemination. This strategy is contrary to the consensus that pleural effusion is a very poor sign for survival among patients with NSCLC; therefore, a patient with malignant pleural effusion should not undergo surgery [1–3].

There are little data on minor pleural effusions detected after thoracotomy in patients with NSCLC. Notwithstanding the fact that malignant minor pleural effusion is defined as T4 in the latest staging system, which was published in 1997 [4], it is not known whether surgery is beneficial for patients with NSCLC accompanied by malignant minor pleural effusion.

We conducted a retrospective study to clarify whether resection is beneficial for patients with NSCLC and minor pleural effusion that is found during thoracotomy.


   Material and methods
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 Abstract
 Introduction
 Material and methods
Results
 Comment
 Acknowledgments
 References
 
We reviewed the records of surgical patients with NSCLC who had undergone surgery at any of the 14 Japanese national referral hospitals between 1980 and 1994. Entry criteria were as follows: (1) pleural effusion was not detected or suspected before surgery and the volume was less than 300 mL; (2) its malignant status was examined; and (3) follow-up was carried out for more than 5 years.

To assess whether surgical resection is beneficial for patients with malignant minor pleural effusion without pleural dissemination, three groups of patients were compared. The first group included patients who underwent grossly complete resection even when they had malignant minor pleural effusion without pleural dissemination (group C); the second included patients who underwent incomplete resection (group I); and the third consisted of patients who underwent exploratory thoracotomy only (group E).

Surgical-pathologic staging was carried out according to the New International Staging System for Lung Cancer [5]. Pleural involvement was classified into four grades based on the Japan Lung Cancer Society classifications [6], as follows: (1) p0 = tumor with no pleural involvement or reaching the visceral pleura but not extending beyond the elastic layer; (2) p1 = tumor extending beyond the elastic and the visceral layer but not to the pleural surface; (3) p2 = tumor exposed on the pleural surface but not involving parietal pleura; and (4) p3 = tumor involving parietal pleura or organs adjacent to the lung.

Survival curves were obtained according to the Kaplan-Meier method. Comparison of survival curves was carried out using the log-rank test. Patient characteristics as well as surgical and pathologic variables were compared using analysis of variance or the {chi}2 test. Statistical calculations were conducted with Stat View (Abacus Concepts Inc, Berkeley, CA); p values of less than 0.05 were accepted as statistically significant.


   Results
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 Abstract
 Introduction
 Material and methods
 Results
Comment
 Acknowledgments
 References
 
There were 196 patients with minor pleural effusion (< 300 mL) at the time of thoracotomy; of these, however, 100 patients (51%) were not examined for malignancy status. Among the remaining 96 patients, all specimens were postoperatively examined to determine malignancy status. There were 43 patients (45%) with malignant minor pleural effusion of which 4 cases (9%) were bloody. Histologic diagnosis was adenocarcinoma in 38 cases, squamous cell carcinoma in 4, and large cell carcinoma in 1. Clinical stage was stage IA in 10 cases, stage IB in 6, stage IIA in 1, stage IIB in 4, stage IIIA in 16, and stage IIIB in 6. No patients underwent induction therapy. Among the 43 patients with malignant minor pleural effusion, 11 underwent grossly complete resection (group C), 14 incomplete resection (group I), and 18 exploratory thoracotomy (group E).

As shown in Table 1, there were no differences in demographic characteristics, histology, or N status. However, both T and P status were at an earlier stage in group C when they were defined excluding the malignant status of the pleural effusion.


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  		Table 1. Characteristics of the 43 Patients With Malignant Minor Pleural Effusion

 
Surgical procedures for each resection group were as follows. In group C there were six lobectomies, one lobectomy with combined resection (chest wall), one pneumonectomy, and three pneumonectomies with combined resection (chest wall, diaphragm, and pericardium). In group I there were two wedge resections, one segmentectomy, seven lobectomies, and three lobectomies with combined resection (one case of chest wall and two cases of both chest wall and diaphragm). There were 3 cases of pleural dissemination that was diagnosed during surgery; therefore limited surgery was undertaken. In 10 cases, the pleural lesions were found to be malignant postoperatively. In 1 case involving residual tumor, pleural dissemination was absent. In group E, 13 patients did not undergo resection because of pleural dissemination and in 5 patients resection was not considered feasible.

Overall, there were 40 patients who died due to lung cancer (27 cases of distant metastasis and 13 cases of local relapse). Among the 13 cases of local relapse, 9 cases were pleural carcinomatosis (2 cases were group C, 2 in group I, and 5 in group E). Survival for all patients with malignant minor pleural effusion was 13 months in MST and 9% in 5-YSR (Fig 1). As shown in Figure 2, survival curves for each group were similar. The median survival time and 5-year survival rate, respectively, were 13 months and 9% for group C, 34 months and 10% for group I (p = 0.3), and 17 months and 0% for group E (p = 0.8).



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  		Fig 1. Survival curve for the 43 patients with malignant minor pleural effusion. Median survival time is 13 months and 5-year survival rate is 5%.

 


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  		Fig 2. Group C patients (ie, patients who underwent grossly complete resection) achieved a median survival time of 13 months and a 5-year survival rate of 9%; group I (patients who underwent incomplete resection) had a median survival time of 34 months and a 5-year survival rate of 10% (p = 0.3); and group E (patients who underwent exploratory thoracotomy) had a median survival time of 17 months and a 5-year survival rate of 0% (p = 0.8). Values were calculated on the basis of a comparison between group C and each of the other groups.

 

   Comment
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 Abstract
 Introduction
 Material and methods
 Results
 Comment
Acknowledgments
 References
 
In the database used to develop the 1974 lung cancer staging system, nonsurgical patients with pleural effusion were found to have an especially poor prognosis [7]. In the 1986 staging revision, pleural effusion was classified as a T4 disease, suggesting a more favorable outcome for these patients than for those with M1 disease [5]. This classification remained unchanged in the 1997 revision [4]. Recently, Sugiura and colleagues [8] compared the survival of 197 patients with stage IIIB without pleural effusion, stage IIIB with pleural effusion, and stage IV disease. They found that the median survival time of the three groups was 15.3, 7.5, and 5.5 months, respectively. The survival curve for stage IIIB patients with pleural effusion was significantly worse than that for stage IIIB patients without, but was not significantly different from that for stage IV patients. These investigators also found that among patients with pleural effusion, there was no significant difference in survival irrespective of whether the pleural fluid was positive for malignancy. It is generally believed that the presence of pleural effusion is a severely poor prognostic factor for survival.

Patients with advanced NSCLC accompanied by pleural effusion cannot undergo operation and therefore should not be treated surgically. Non–small cell lung cancer with pleural effusion is classified as a high-stage disease. In contrast, a review from the Mayo Clinic [9] demonstrated that even cytologically negative pleural effusion was predictive of unresectability in 95% of these patients; nevertheless, 5% of them were found on thoracotomy to have limited resectable disease, and all were long-term survivors. These researchers concluded that among patients with cytologically negative effusion, resectability must be documented surgically. Naruke and colleagues [10] reported that the 5-year survival rate of 40% among 112 patients with nonmalignant effusion was similar to the 5-year survival rate among 1,298 patients without pleural effusion. They concluded that surgical resection seems favorable when the pleural effusion is not malignant.

Positive malignancy in pleural lavage during thoracotomy is reported as an unfavorable prognostic factor for patients with NSCLC without malignant pleural effusion or pleural dissemination [11–15]. Therefore, the malignant status of pleural effusion may be a poor prognostic factor for patients with minor pleural effusion without pleural dissemination. Ratto and colleagues [16] demonstrated the prognostic significance of minor pleural effusion for surgical patients with NSCLC. They found that patients with minor pleural effusion showed a median survival time of 14 months. In the 50% of this group who underwent resection, this time increased to 37 months. However the significance of positive malignancy for long-term survival cannot be inferred from their report, because 19 of 20 patients (95%) showed negative malignancy for the pleural effusion. Our study revealed that 45% of the minor pleural effusion was malignancy positive, and patients who underwent grossly complete resection, notwithstanding a malignant minor pleural effusion, had a median survival time of 13 months and a 5-year survival rate of 9%. This is similar to that of patients who underwent either incomplete resection or only exploratory thoracotomy.

Shimizu and colleagues [17] studied pleuropneumonectomy in comparison to limited surgery plus parietal pleurectomy among patients with NSCLC accompanied by pleural dissemination. This study revealed the 5-year survival rate for pleuropneumonectomy to be 19% and for limited surgery plus parietal pleurectomy 35.5%. Shiba and associates [18] studied the prognosis of patients with NSCLC along with subclinical malignant pleural effusion. According to their investigation, the 5-year survival rate for patients without macroscopic dissemination was 22.9%. These patients underwent pleural therapy by exposure to mitomycin-C at the time of closing. Adjuvant therapy or moderately aggressive resection may be beneficial for the survival of patients with NSCLC along with malignant pleurisy.

Thoracoscopic surgery has become available and, thus, the status of pleural effusion and the pleural space can be examined with limited intervention before thoracotomy [19, 20]. In our present study, distant metastasis was the cause of death in 68% of cases; therefore, induction therapy may be beneficial. If thoracoscopic surgery were undertaken before thoracotomy to explore the status of pleural effusion, induction therapy might be carried out for patients with malignant minor pleural effusion.

In conclusion, surgical resection is not beneficial for patients with malignant minor pleural effusion, even if there is no pleural dissemination, due to the poor prognosis for this disease. Patients who underwent either incomplete resection or exploratory thoracotomy had a similarly poor prognosis. A trial of aggressive resection including the pleura or multimodality treatment is warranted for patients with NSCLC together with malignant minor pleural effusion.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
References
 
We appreciate the cooperation of the members of The Japan National Chest Hospital Study Group for Lung Cancer: Yuka Fijita, MD (North Hokkaidou National Hospital); Tatsuo Saito, MD, and Osamu Kawashima, MD (Gunma-Nishi National Hospital); Toshimasa Tuchiya, MD, Tatsuhiko Hirono, MD, and Yasuhiro Watanabe, MD (Nigata-Nishi National Central Hospital); Yoshinori Hiramatsu, MD (Chubu National Hospital); Tadashi Maeda, MD, and Shigeki Makihara, MD (Sannyousou National Hospital); Takakazu Fukushima, MD (Kumamoto-Kita National Hospital); Fumiyuki Iwami, MD, and Ichiro Kubota, MD (Kyusyu-Minami National Hospital); Atsuhiko Tada, MD, and Motohiro Yamashita, MD (Kita-Okayana National Hospital); Masayuki Hyuuda, MD (Cyushin Matsumoto National Hospital); and Hajime Maeda, MD (Toneyama National Hospital).


   References
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 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 

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  7. Mountain C.F., Carr D.T., Anderson W.A.D. A system for the clinical staging of lung cancer. Am J Roentogenol 1974;120:130-138.
  8. Sugiura S., Ando Y., Minami H., et al. Prognostic value of pleural effusion in patients with non–small cell lung cancer. Clin Cancer Res 1997;3:47-50.[Abstract]
  9. Decker D.A., Dines D.E., Payne W.S., et al. The significance of a cytologically negative pleural effusion in bronchogenic carcinoma. Chest 1978;6:640-642.
  10. Naruke T., Goya T., Tsuchiya R., Suematsu K. Prognosis and survival in resected lung carcinoma based on the new international staging system. J Thorac Cardiovasc Surg 1988;96:440-447.[Abstract]
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