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Eur J Cardiothorac Surg 2001;19:899-903
© 2001 Elsevier Science NL

Surgical management of metachronous bronchial carcinoma

Department of Thoracic Surgery, Sainte Marguerite University Hospital, Marseille France

Received 14 November 2000; accepted 19 March 2001.

Corresponding author. Tel.: +33-491-744741; fax: +33-491-744590
e-mail: cdoddoli{at}mail.ap-hm.fr

	Abstract

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion Appendix A. Conference... References

 
Objective: To assess the results of surgery for the treatment of metachronous bronchial carcinoma. Methods: From 1985 to 1999, 38 patients were operated on for a metachronous lung carcinoma, accordingly to the criteria of Martini. All tumors were staged using the new International Classification System revised in 1997. Results: Diagnosis of the second cancer was done at radiological follow-up in 30 asymptomatic patients. Seventeen metachronous locations were ipsilateral. Histology of the metachronous lesion was the same as that of the first tumour in 23 patients (60%). The first resection was a lobectomy (n=35), a pneumonectomy (n=2) and a carinal resection (n=1). The second one was a wedge resection (n=7), a segmentectomy (n=3), a lingulectomy (n=2), a lobectomy (n=9), a bilobectomy (n=1), and a pneumonectomy (n=16). There were five in-hospital deaths (13%). Completion pneumonectomy was performed in 15 patients, with one postoperative death (7%). The overall estimated 5 and 10-years actuarial survival rates from the treatment of the first cancer were 70 and 47% respectively. The 5-year survival rate after the treatment of the second cancer was 32% (median survival: 31 months), including the operative mortality. Survival was negatively affected by a resection interval of less than 2 years and the performance of atypical lung sparing pulmonary resection for the treatment of the second cancer. Conclusions: Good long-term results are achievable by the means of a second pulmonary resection in selected patients with metachronous lung cancer. Optimal cancer operations should be applied whenever functionally possible.

Key Words: Second primary lung cancer • Resection • Follow-up

	1. Introduction

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion Appendix A. Conference... References

 
A patient operated on for a non-small cell lung cancer has approximately a risk of developing a second primary lung cancer of 2% per year [1]. The aim of our study was to assess the results of surgery for the treatment of metachronous bronchial carcinoma over the past 15 years. The definition of a metachronous lung carcinoma remains at the present time prone to discussion. We used the criteria defined by Martini and Melamed [2] for the diagnosis of metachronous lung cancers.

	2. Methods

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion Appendix A. Conference... References

 
We reviewed the medical records of all patients who underwent operation for a metachronous lung cancer between January 1985 and December 1999. There were thirty-eight patients found. We used the criteria established by Martini and Melamed [2] for the diagnosis of metachronous lung cancer. The first and second tumors were staged using the new International Classification System revised in 1997 [3].

This population accounted for 2% of all the patients operated on for a primary lung cancer during this same period. Absence of detectable extrathoracic disease on brain CT scan, abdominal CT scan and bone scanning was required to include these patients. Operative mortality included all deaths occurring within 30 days after pulmonary resection or during the same hospital stay. Survival was calculated by the Kaplan–Meier method and hospital deaths were included in the survival figures. The log-rank test was used to compare survival rates between groups. Probability values of 0.05 or less were considered statistically significant. Data are presented as mean±standard deviation. The follow-up was complete for all patients.

	3. Results

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion Appendix A. Conference... References

 
3.1. Diagnostic circumstances
There were 35 men and 3 women. The average age at the time of treatment for the second tumor was 63±8 years. The diagnosis of the metachronous lung cancer was made during the follow-up period, either by chest X-ray or CT scan (30 patients) or by bronchial fiberscopy (one patient). Only seven patients were symptomatic. Among the radiological discoveries, 28 were found on the chest X-ray and two on a chest CT scan. For these two last cases, the chest X-ray was normal. The circumstances of diagnosis in symptomatic patients were: hemoptysis (four), chest pain (one), cough (one) and loss of weight (one). Seventeen metachronous locations were ipsilateral, and 21 controlateral. Eight patients (21%) had a history of extrapulmonary primary cancers: laryngeal cancer in four cases, renal cancer in two cases, prostate cancer in one case and oesophagus cancer in one case. All of these patients had previously been treated curatively for their nonpulmonary cancer with no evidence of recurrence at the time of diagnosis of the metachronous lung carcinoma.

3.2. First primary lung cancer
When the diagnosis of the first tumor was made, 37 patients were smokers. The first operation was a lobectomy in 35 patients, a pneumonectomy in two patients and a carinal resection in one patient. The postoperative stages were as follow: 10 IA, 18 IB, two IIA (T2N1), three IIB, and five IIIA (four T2N2 and one T3N1). There were 20 squamous cell carcinoma, 14 adenocarcinoma and four undifferentiated carcinoma. Five patients had a postoperative treatment, by radiochemotherapy in three patients and chemotherapy in two patients.

3.3. Metachronous lung cancer
At the time of the metachronous lung cancer diagnosis, most patients were heavy smokers (87%). The interval between the two operations of the lung was 60±52 months (7 months to 17 years). Among the ten patients who had an interval time of less than 2 years, four had a histologically different tumor. No patient had a preoperative treatment. The operation consisted of a pneumonectomy in 16 cases including 15 completion (previous lobectomy), a lobectomy in nine cases, a bilobectomy in one case, a limited resection in 12 cases (seven wedges resections, three segmentectomies and two lingulectomies). Among these last 12 patients, seven had a functionally contraindication to have a more extensive resection. Among them, two had had a pneumonectomy for the treatment of the first cancer. The postoperative stages were as follow: nine IA, 18 IB, one IIA (T2N1), three IIB, three IIIA (T2N2) and four IIIB (T4 by separate tumors nodules in the same lobe, N0). The histological types were identical for the two tumors in 23 patients (60%) (Table 1).

The overall estimated 5 and 10-years survival rates after pulmonary resection for the first cancer were 70 and 47%, respectively. The 5-year survival rate after pulmonary resection for the second cancer was 32% (median survival: 31 months), including operative mortality. Five-year survival of patients who developed a second metachronous lesion sooner or later than 2 years, and 5-year survival of patients who underwent a limited resection versus a standard resection are presented in Figs. 1 and 2, respectively. Survival was negatively affected by a resection interval of less than 2 years and the performance of atypical lung sparing pulmonary resection for the treatment of the second cancer. However the difference did not reach the statistical significance.

View larger version (14K): [in this window] [in a new window]   Fig. 1. Survival curves of patients in whom the metachronous lung cancer developed after or before 2 years.

View larger version (15K): [in this window] [in a new window]   Fig. 2. Survival curves of patients who had standard resection versus limited resection.

	4. Discussion

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion Appendix A. Conference... References

 
The metachronous lung carcinoma was detected essentially in asymptomatic patients, during the follow-up period. This concept, as previously reported [4,5], is in favour of a thorough follow-up of all patients operated on for a lung cancer. A second pulmonary cancer can occur several years after the first cancer diagnosis [6,7]. In our study, one patient was operated on a second cancer 17 years after the diagnosis of the first cancer. These data suggest that patients surviving treatment of a first primary lung carcinoma require lifelong screening of second primary lung cancer. We recommend a close follow-up the first 2 years, then semi-annual until the fifth year and then after this an annual follow-up. This follow-up must include at the very least a clinical examination and a chest X-ray. The chest X-ray gave the diagnosis in 28 patients (74%).

Considering our patients, 21% had a history of primary extrathoracic cancer. Deschamps reported a rate of 21.3% in patients with multiple primary lung cancer [8]. The study published by Levi [9] showed that there is an increased risk of developing a tobacco-related neoplasm as well as lung carcinoma after the diagnosis of a first lung cancer.

The characteristics of the first resected cancer was predominantly stage I or II (87%). This data is also reported in others series [4,5,8] of metachronous bronchial cancer. A patient who has initially an advanced stage tumor has a poor chance to survive long enough to develop another primary lung cancer.

The characteristics of the second cancer suggest two remarks: the histologic types were identical for the tumors in 23 patients (60%) and early stage (I or II) represented 82% of the patients. These data are also those usually found in the literature [4–6,8]. Our postoperative follow-up allowed us to detect earlier second tumors amenable to a Re resection.

Despite our strict patient selection, the postoperative mortality rate was 13%. Whereas Angeletti [4] and Okada [5] had no postoperative mortality, other authors reported a rate similar to our series [10,11]. Thirty seven percent of patients required a per and/or postoperative blood transfusion. This was explained by the rate of completion pneumonectomy which accounted for 39% of the resections. These interventions are known to be haemorrhagic. The two postoperative hemothorax were observed after completion pneumonectomy. In our series, patients undergoing Re resection for metachronous lung cancer had a 11% non-fatal major complication rate, which is comparable to that previously reported for patients undergoing pulmonary resection for initial lung carcinoma. Most of the reports dealing with the surgical management of a second primary lung carcinoma did not give data concerning postoperative complications. Deschamps et al. [8] reported a 38.6% complication rate.

Limited resection, were performed in 12 patients (32%). For seven patients, the pulmonary function did not allow for a more extensive resection. Among them, two patients had had a pneumonectomy at the time of the first operation. Spaggiari et al. [12] also reported a series of limited pulmonary resection for lung cancer after pneumonectomy for bronchogenic carcinoma: surgical resections consisted of segmentectomy or wedge resection. In their experience, there was no postoperative death and overall median survival time was 19 months. Therefore a patient who had had a pneumonectomy for bronchogenic lung carcinoma must not be contraindicated systematically for a Re resection on the residual lung. For the five other patients who had a lung sparing resection, the goal was to prevent postoperative complications. In our series, one patient died after a wedge resection; however the death was not related to the respiratory status. Deschamps [8] and Ribet [10] reported a rate of limited resection of 43 and 26%, respectively. They did not give detailed information about the indications of these limited resections.

The 5-year survival rate after the treatment of the second cancer was 32% (median survival: 31 months), including operative mortality. The rates usually reported [4–6,8,10] range from 25 to 30%. Our population of patients was selected with 82% of early stage tumors. One should be careful with a preoperative staging selection using CT findings only. Any suspected N2 disease should be documented by mediastinoscopy or videothoracoscopy. In fact, mediastinoscopy might be proposed routinely before a pulmonary Re resection in those patients.

Survival seemed to be negatively affected by a resection interval of less than 2 years. This is probably explained by the fact that some secondary lung cancers considered as metachronous were in fact a recurrent or a metastatic pulmonary disease. This may be suspected especially when the histology between the two tumors was identical. In our series, only six patients presented these conditions. One should highlight, however, that histology of the second tumour was often obtained on the specimen analysis. Thus it seems justified to continue to operate all patients with a single pulmonary lesion suspected to correspond to a metachronous lung cancer. Regarding the data reported in the literature, it seems that only an immunohistologic study [13,14] will allow for a differential diagnosis between a recurrent or metastatic pulmonary disease, and a metachronous lung cancer when the histology of the two tumors are identical.

Survival seemed to be negatively affected by the performance of atypical lung sparing pulmonary resection for the treatment of the second cancer. This confirms that atypical lung sparing resections are not ideal from an oncological point of view [15]. Thus a resection should be proposed whenever functionally possible. All lung resections must satisfy the oncological principles for cure. Obviously reaching these oncological principles is not possible when the first resection was a pneumonectomy. In accordance with this situation, it may be useful to consider more sleeve resection whenever it is possible, instead of pneumonectomy at the first surgical resection.

Our series show that a history of another extrathoracic cancer should not be a contraindication to a lung resection, if it was treated in a curative way. This data was also reported by Massard [16] for the initial management of primary lung cancer and Deschamps [8] in case of metachronous lung cancer.

5. Conclusions
Good long term results are achievable by means of a second pulmonary resection in selected patients with metachronous lung cancer. Optimal cancer operations should be applied whenever functionally possible.

	Footnotes

 
Presented at the 14th Annual Meeting of the European Association for Cardio-thoracic Surgery, Frankfurt, Germany, October 7–11, 2000.

	Appendix A. Conference discussion

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion Appendix A. Conference... References

 
Dr T. Dosios (Athens, Greece): I noticed that about one-third of your patients were in advanced stage when you diagnosed the second primary tumor. It is well known that the long-term survivors after the first operation are at the top of the high-risk patients for development of another lung cancer. For this reason, I think we should follow them more closely. By this way, we can diagnose the cancer or the second primary tumor at an earlier stage.

The problem is that there is no general agreement as to how often we should follow these patients. As you know, a study was done in Europe some years ago and it was found that one out of four thoracic surgeons in Europe does not see his or her patients after the operation at all. I think EACTS should develop a policy regarding the postoperative follow-up of the patients after resection of lung cancer.

Dr V. Sa Vieira (Lisbon, Portugal): I think it is a good proposal. Probably at the next meeting we can do a proposal to the audience or a paper demonstrating what you think is the best policy for following a patient after the resection.

Dr Dosios: There was a presentation at this meeting 5 years ago and a paper was published in our journal about the same subject (Eur J Cardio-thorac Surg 1996;10:1052).

Dr F. Rea (Padova, Italy): Regarding the segmental resection, we find that you have a worse prognosis in this subset. Did you look at this subset of patients and did you study which kind of stage this group of patients had?

Dr Thomas: We had only 12 patients who had a lung-sparing operation, so most of them had stage I disease, but I think that the sample size precludes any definite conclusion.

Dr G. Massard (Strasbourg, France): You pointed out and you told me even yesterday evening that you were not very satisfied with your operative mortality. So I would like to ask you if perhaps one factor that we observed in our experience applies to your series. You had about one-third of the patients who had a stage IIIA cancer at the first step. How many of these patients had radiation therapy? We believe that previous radiation therapy on the hilum severely compromises the lung function and also the defense mechanisms against infection, and these patients, to my opinion, are at high risk for getting postoperative pneumonia on the irradiated side. What do you think about it?

Dr Thomas: The five patients who had stage IIIA disease at the time of the treatment of the first cancer received postoperative therapy, including radiotherapy, and of these, three experienced pneumonia at the time of the second operation, exactly as you said.

Dr Sa Vieira: Did you find any difference in survival between the patients with metachronous tumors but with different histologic types?

Dr Thomas: No. There were strictly no differences.

Dr K. Jeyasingham (Winterbourne Down, UK): Dr Thomas, by definition, a second primary would mean more than 2 years after the first was resected, but in your analysis there is a series which you had analyzed where they were less than 2 years. Were there other criteria that conformed to your definition?

Dr Thomas: Yes. We classified our patients according to Martini criteria. In case of different histology, delay is not routine.

	References

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion Appendix A. Conference... References

 

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