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Ann Thorac Surg 1998;66:214-218
© 1998 The Society of Thoracic Surgeons

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Original articles: general thoracic

Surgical treatment of hepatic and pulmonary metastases from colorectal cancers

^a Department of Thoracic Surgery, Marie Lannelongue Hospital, Paris, France
^b Department of Thoracic Surgery, Institut Mutualiste Montsouris, Paris, France

Accepted for publication January 24, 1998.

Address reprint requests to Dr Regnard, Department of Thoracic Surgery, Marie Lannelongue Hospital, 133 ave de la Résistance, 92350, Le Plessis Robinson, Paris, France

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
Background. Selected patients with double hepatic and pulmonary metastases from colorectal cancer may benefit from operation.

Methods. From 1970 to 1995, 239 patients underwent operation for resection of pulmonary metastases from colorectal cancer at two French surgical centers. Among these patients, 43 (18%) had previously undergone complete resection of hepatic metastases and constitute the subject of this retrospective study.

Results. The median interval time between hepatic and pulmonary resections was 18 months. Two pneumonectomies, 5 lobectomies, 3 segmentectomies, 6 wedge resections, and 27 metastasectomies were performed. No postoperative mortality was observed. Two patients had major postoperative complications. Seven patients (16%) underwent subsequent pulmonary resection for recurrences. Twenty-one patients were still alive, 14 free of disease. The median survival from pulmonary resection was 19 months and the 5-year probability of survival was 11%. Prethoracotomy carcinoembryonic antigen blood levels and the number of pulmonary resection were found to be significant prognostic factors; the interval time between hepatic and pulmonary resection (>36 months) was borderline significant (p = 0.06).

Conclusions. Selected patients with combined hepatic and pulmonary metastases from colorectal cancer should be considered for surgical resection. Patients with normal prethoracotomy carcinoembryonic antigen levels and late metachronous pulmonary metastasis, appear to be the best surgical candidates.

	Introduction

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Patients with untreated metastatic colorectal cancer have a median survival of less than 10 months with a 5-year probability of survival of less than 5% [1]. The liver and the lungs are the main sites of the spread of this disease, and hepatic and pulmonary metastases are frequently associated. The disappointing results of chemotherapy explain the attempts of surgical resections of either hepatic or pulmonary colorectal metastases. However, resectable hepatic and pulmonary metastases are rare; in fact, only 2% to 4% of pulmonary metastases from colorectal cancer can be treated surgically [2–4], and this percentage is about 1% for hepatic metastases [5]. Nowadays resection of colorectal metastases has become an effective treatment in selected patients with a postoperative mortality of about 5% and a 5-year probability of survival ranging from 25% to 42% [6–10]. Likewise, the resection of pulmonary metastases from colorectal cancer could result in a 5-year probability of survival ranging from 21% to 43% and a 10-year probability of survival of 20% [11, 12].

These encouraging results suggested widening surgical indications to patients with both hepatic and pulmonary metastases. Yano and colleagues [13] reported 6 patients with a 3-year probability of survival of 68% that was similar to that of the 20 other patients who underwent surgical resection of metastases confined to the lungs. Elias and colleagues [14] reported a group of 5 patients of whom 3 were still alive and free of disease at 7 years and 6 years 22 months, respectively, after operation. Gough and coworkers [15] reported the Mayo Clinic experience with 9 patients with a median survival of 27 months; however only 2 patients were alive and free of disease 11 months and 62 months, respectively, after the first resection. Recently, Minnard and colleagues [16] reported the Memorial Sloan-Kettering Cancer Center experience concerning 33 patients; the median survival after the last resection was 24.5 months.

These series do not allow definition of the place of operation in patients with both hepatic and pulmonary metastases; in fact, the rarity of patients with combined hepatic and pulmonary resectable metastases does not permit a single institution to have a larger series. Thus, we decided to pool two French series with the purpose of reaching a sufficient number of patients. Reviewing our immediate and long-term results, we tried to identify prognostic factors for the selection of the patients who may benefit from operation.

	Material and methods

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From January 1970 to December 1995, 239 patients underwent resection of pulmonary metastases from colorectal cancer in two different Departments of Thoracic Surgery (Marie Lannelongue Hospital and Institut Mutualiste Montsouris) in Paris. Among these patients, 196 were operated on for metastases confined to the lung, whereas 43 (18%) consecutive patients had previously undergone resection of hepatic metastases. All of these patients were operated on since 1982 and they constitute the subject of this retrospective study.

There were 25 men and 18 women, with a mean age of 54 years (range, 34 to 72 years) at the time of the pulmonary resection. Table 1 reports the main clinicopathologic data regarding primary colorectal cancer. Five patients developed local colonic or rectal recurrences before hepatic resection; they underwent a re-resection with an interval time between the two colorectal operations ranging from 3 to 28 months. The median interval time between the resection of the primary tumor and the hepatic metastasectomy was 12 months (range, 0 to 108 months).

Table 3 reports the main clinicopathologic data concerning lung metastasectomies. Mediastinal lymph nodes sampling was always performed. In 6 patients (14%) a positive lymph node involvement was observed. All but 1 patient had a complete lung metastasectomy.

	Results

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No postoperative mortality was observed. Forty-one patients (95%) had an uneventful postoperative course. One patient had an empyema that was medically treated and another had a postoperative hemorrhage that required reintervention. Twenty-eight patients had postoperative chemotherapy.

Seven patients (16%) were reoperated on for lung recurrences. The recurrences were a solitary nodule in 2 patients, multiple unilateral nodules in 3, and multiple bilateral nodules in 2 patients. One patient required a bilobectomy, 3 a lobectomy, and 3 patients wedge resections. Four patients (9%) underwent a third lung metastasectomy: 1 had a lobectomy, 2 had multiple wedge resections, and the last one had a single wedge resection.

At the completion of the study, 21 patients were still alive, 14 free of disease; the remaining patients died of their colorectal metastatic disease mainly because of lung and liver recurrences. The median survival of the overall population was 19 months (range, 6 to 72 months). The 5-year probability of survival was 11% (95% confidence interval, 2% to 39%).

Sex, stage of the primary tumor, number of resected hepatic and pulmonary metastases (solitary hepatic metastasis and solitary pulmonary metastasis versus multiple), number of hepatic resections before pulmonary resections, synchronous versus metachronous metastases; prethoracotomy chemotherapy, thoracic lymph node involvement, and interval time between colorectal and hepatic resections were not significant prognostic factors. No significant difference was observed between the group of patients with both hepatic and pulmonary metastases and the group of patients with metastases confined to the lungs (Fig 1). Finally, only three significant prognostic factors were found: the CEA blood level, the number of pulmonary resections, and the interval time between hepatic and pulmonary resections. In fact, analyzing the probability of survival of patients with tested prethoracotomy CEA blood levels (n = 37), we observed that patients (n = 16) with normal (<5 ng/mL) CEA levels had a significantly higher probability of survival than those (n = 21) with elevated (>5 ng/mL) CEA levels (p = 0.0018) (Fig 2). In addition, the 7 patients who required more than one pulmonary resection had a significantly better survival than those requiring only one resection (n = 36) (p = 0.035). Finally, patients with an interval time between hepatic and pulmonary resections of more than 36 months (n = 8) seemed to have a better outcome than those with an interval time of less than 36 months (n = 35), but the difference is not quite significant (p = 0.06).

View larger version (12K): [in this window] [in a new window]   Fig 1. Estimated probability of survival of patients with resected hepatic and pulmonary metastases from colorectal cancer (n = 43), and of patients with "lung only" resected metastases (n = 196). The 5-year probability of survival was 11% (95% confidence interval, 2% to 39%) in the hepatic/pulmonary metastases series, whereas in the "lung-only" metastases series it was 27% (95% confidence interval, 18% to 33%) with a 10-year probability of survival of 17% (95% confidence interval, 10% to 26%). The comparison by means of log-rank test was found to be not significant. The numbers in parentheses at 5 and 10 years indicate the number of patients still at risk at the corresponding date.

View larger version (12K): [in this window] [in a new window]   Fig 2. Estimated probability of survival of patients according to prethoracotomy carcinoembryonic antigen (CEA) blood levels. Patients with normal CEA blood levels (<0.5 ng/mL) (n = 16) had a significantly higher probability of survival than those (n = 21) with elevated (>0.5 ng/mL) CEA blood levels (log-rank test p = 0.0018).

	Comment

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At the time of the pulmonary resection, the selection of the candidates for operation was done according to the classic criteria for pulmonary metastasectomy. The type of hepatic resection, the number of resected hepatic metastases, as well as the disease-free interval between the primary tumor and the metastases did not contraindicate pulmonary resections; besides, multiple and bilateral pulmonary metastases did not contraindicate thoracic operation. These indications explain the frequency of patients with both multiple hepatic and pulmonary metastases that were surgically treated in this series.

The overall survival of these patients (n = 43) did not significantly differ from that of the 196 patients operated on for metastases confined to the lungs in the two institutions (see Fig 1). However, the lack of statistical difference in survival between patients with and without previous hepatic metastasectomies should be interpreted with caution. In the group of patients with both hepatic and pulmonary metastases, no 6-year survivors have yet been observed, although in the group of patients with metastases confined to the lungs, the 10-year probability of survival was 17% (see Fig 1). Two considerations may explain this finding. First, the group of patients with combined hepatic and pulmonary metastases is still small with a relatively short follow-up. Second, the presence of combined metastases may have a worse prognosis even if the difference between the curves is not significant. Therefore, a larger number of patients with combined resectable metastases and a longer follow-up are necessary before the therapeutic value of this aggressive surgical approach could be clearly established.

Two prognostic factors were found in the present series: the prethoracotomy serum CEA levels and the number of pulmonary resections performed. Serum CEA levels reflect both the total tumor mass and the capability of tumor cells to express CEA. This antigen participates in intracellular recognition as well as in the promotion of the adhesion of tumor cells among them or to host cells; thus, elevated CEA levels may be associated with a higher probability of development of metastatic disease [17]. Accordingly, it has been demonstrated that patients with elevated serum CEA levels before resection of the primary colorectal cancer [18] and before resection of hepatic metastases from colorectal cancer [19, 20] have a significantly worse prognosis. Recently, Elias and colleagues [21] demonstrated by a multivariate analysis that CEA levels was an independent prognostic factor in a series of patients with hepatic metastases from colorectal cancer who received intraarterial chemotherapy. Concerning pulmonary metastases, McAfee and colleagues [12] observed that patients with normal prethoracotomy serum CEA levels who underwent pulmonary metastasectomies had a significantly higher 5-year survival than those with normal CEA levels and the data have been recently confirmed by our pooling series [22]. In the present series, even if characterized by a highly selected population, we confirmed the prognostic value of prethoracotomy CEA levels.

Another significant prognostic factor in this series was the number of pulmonary resections performed. In fact some patients with limited recurrent pulmonary metastases apparently benefitted from further pulmonary resections with long-term disease-free survivals. Girard and colleagues [23] found the same results, but the interpretation of this "prognostic factor" remains uncertain.

The interval time between hepatic and pulmonary metastasectomies was a borderline significant factor, especially when the interval time was more than 36 months. In our published series concerning pulmonary metastases [24], we found that the disease-free interval was a significant prognostic factor with a better survival for patients with metachronous pulmonary metastases; this result was in accordance with the series of Van Halteren and coworkers [25], but McAfee and associates [12] did not find the same results. In the Memorial Sloan-Kettering Cancer Center series, patients with synchronous hepatic and pulmonary metastases had a significantly worse prognosis than those with metachronous metastases [16]. However, in our opinion, synchronous hepatic and pulmonary metastases or a short disease-free interval is not an absolute contraindication for operation in patients with otherwise resectable hepatic and pulmonary metastases. In the present series, we did not find any other prognostic factors, but this is not surprising considering that in most series studying hepatic or pulmonary metastasectomies from colorectal cancer, no other prognostic factors were identified [11, 12, 24, 25].

Surgical resection of hepatic and pulmonary metastases can be performed with a very low rate of postoperative complications; as a result, an aggressive approach could be attempted in some patients. Prethoracotomy chemotherapy may be used, even if we did not find any difference in the survival between patients who received chemotherapy and those who did not. Probably a prethoracotomy chemotherapy may exclude patients with rapidly evolving disease that are not good candidates for surgical resections.

Despite the relatively large number of patients in our series, our results do not allow definitive conclusions regarding the long-term benefit of this operation for patients with both hepatic and pulmonary metastases from colorectal cancer; more patients and a longer follow-up are needed to firmly establish the place of this approach. At present, patients with normal CEA levels and late metachronous metastases are probably the "best" surgical candidates in this setting, but the respective indication of chemotherapy and operation should still be discussed on a case-by-case basis before more reliable data are available.

	References

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