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Eur J Cardiothorac Surg 2000;18:529-534
© 2000 Elsevier Science NL
Thoracic Surgery Unit, University Hospital of Siena, Viale Bracci n. 1, 53100 Siena, Italy
Received 8 September 1999; received in revised form 2 August 2000; accepted 5 September 2000.
Corresponding author. Tel.: +39-0577-585731; fax: +39-0577-586168
e-mail: carla{at}biolab.med.unisi.it
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Abstract |
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 Top Abstract 1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Key Words: Bronchogenic carcinoma • Local recurrence • Second primary lung cancer • Completion pneumonectomy
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1. Introduction |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Consequently, it is very important, although sometimes very difficult in clinical practice, to distinguish between a new lung cancer and a recurrence of the first tumour. However, we believe that with an aggressive follow-up, early detection of recurrence is possible and some selected patients can benefit from surgical therapy. The extent of resection is also an area of concern in treating a SPLC or a recurrence. Recommended treatments have ranged from lesser resection or non-operative treatment for what was considered recurrent disease, to standard lobectomy or completion pneumonectomy, when possible.
The aim of this study is to report our experience with the iterative surgical resections for local recurrent and SPLC focusing on morbidity, mortality and survival characteristics of these two groups of patients.
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2. Materials and methods |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Variables analyzed included type of operation, histology, time between the two surgical interventions, operative finding, operative and post-operative complications and hospital mortality, as well as late death.
Tumour histology was classified according to the World Health Organization Classification [9]. All cases of bronchio–alveolar carcinoma were excluded only because of the question of multicentricity of those primary cancers.
Staging was done according to the International TNM Classification for Lung Cancer [10] and was based on data obtained from imaging, bronchoscopy, invasive diagnostic techniques, operative findings, and pathologic findings. Mediastinoscopy was selectively performed in suspected N2 disease on high resolution CT scan, to exclude patients with N2 disease from operation.
Careful intra-operative staging was done by dissecting intrapulmonary, hilar and ipsilateral mediastinal nodes.
A set of criteria modified from Martini and Melamed [11] were applied to differentiate between recurrent and SPLC. A neoplasm was defined as a local recurrence if it was histologically similar to the original tumour and occurred in an area anatomically contiguous to the resected area, in the bronchial stump, in hilar or mediastinal lymph-nodes (despite a careful mediastinal lymph-nodes dissection at the first operation), or in the mediastinal fat. All other sites of recurrence were referred to a distant recurrence. A neoplasm was considered a SPLC when a neoplasm of different cell type developed in lung parenchima.
For tumour with a cell type similar to that of the original lesion, a new cancer was considered a second primary when it occurred outside the area defined as a local recurrence with no carcinoma in lymphatics common to both, no extrapulmonary metastases at the time of diagnosis, and when the new lesion was a solitary one in lung parenchima.
Follow-up was complete and closed on February 28, 1999. The Kaplan–Meier method was used for calculation of survival rates, and differences in survival were determined by log-rank analysis.
Hospital mortality (all intra-operative and post-operative deaths during hospitalization or within 30 days after operation) was included in calculation of survival rate.
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3. Results |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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3.1. Group 1: recurrences
Four hundred and eighteen patients (3.9%) had tumour recurrence, of whom 49 (12%) with local tumour recurrence only. Of these 49 recurrent lesions, 21 were judged to be resectable, but surgery was denied to nine patients because of poor cardiopulmonary reserve or concomitant illness. Thus, 12 patients underwent a second pulmonary resection. There were ten men and two women. Mean age at the time of the first operation was 61 years (range, 41–78 years). Recurrent lung cancer was initially suggested by chest radiography alone in nine cases, by sputum cytological findings alone in one, by bronchoscopy in one, and by a combination of these methods in one. Only two patients were symptomatic at the time of detection. In the other ten patients the recurrence of cancer was detected at the scheduled 4–6-months examination.
The local recurrences developed at a mean interval of 24 months (range 4–83).
Sites of recurrence, interval between the 1st operation and tumour recurrence and survival after the 2nd operation are described in Table 1. Table 2 shows operative procedures, histology and postoperative staging.
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The second resection was considered radical in all but one patient; adjuvant therapy was administered to three patients: two of which received chemotherapy and the other chemo- and radio-therapy.
Complications occurred in four out of 12 patients, and included cardiac arrhythmias in two patients, recurrent nerve paralysis in one and empyema in another patient. One patient died intraoperatively of fatal bleeding, because of laceration of the pulmonary artery. The mean follow-up for the 11 patients who survived the second operation was 21 months (range, 2–60 months). Currently, four out of 12 patients are alive and free of any known recurrent cancer after 27, 2, 6 and 60 months from the second operation, respectively. Of the eight patients who have died, recurrent lung cancer was known to be present and to be the cause of death in six. One patient died intraoperatively and another patient died of unrelated cause.
Five-year survival after the second operation was 15.5% with a median survival of 26 months (Fig. 1) .
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Among 15 patients who were operated on also for the second lung tumour, two were women and 13 men. Average age at presentation of the first primary cancer was 65.5 years (range 43–78).
The criteria used to define that the second lung tumour was a new primary cancer consisted of different cell type in seven patients, controlateral pulmonary location in seven, and location in a different ipsilateral lobe in one.
Type of resections, histology, postoperative staging and interval between the first and the second operations are shown in Table 3.
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All stage III A patients received postoperative irradiation.
Complications occurred in five patients (33.3%) after the second pulmonary resection and included cardiac arrhythmia in one, prolonged air leak in three, and bronchial stenosis resolved after the placement of a bronchial silicone stent in one. One patient of the three who presented prolonged air leak died in the postoperative period because of respiratory failure, for a mortality rate of 6.6%. The mean follow-up for the 14 patients who survived the second operation was 24 months (range 2–60 months).
Currently eight out of 15 patients are alive, without evidence of recurrent cancer. Among the seven patients who have died, recurrent lung cancer was the cause of death in six.
Five-year survival of group 2, from the time of the second resection, was longer than that of group 1, without statistical significance (Fig. 1).
Overall hospital mortality of patients of both groups (27 patients) was 7.4%. The overall 5-year survival rates following the second operation was 30% (Fig. 2) .
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4. Discussion |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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The indication in re-operations depends also on the site and stage of recurrent tumour and the time between first resection and tumour recurrence. A radical resection of recurrent lung cancer can be attempted in a considerable percentage of peripheral recurrent tumour, but very rarely, if ever, in hilar recurrent cancer. Patients with hilar recurrent neoplasm often present a widespread mediastinal involvement, precluding any possibility of curative resection.
We attempted re-thoracotomy in only one patient with a mediastinal recurrence, whereas the major part of our patients (67%) presented intrapulmonary recurrence. Before proceeding to re-operation for local recurrence, the clinical staging must be as accurate as possible. Patients are completely scanned for distant metastases even in the absence of symptoms or abnormal liver function. Moreover, it is our practice to perform mediastinoscopy because the presence of mediastinal lymphnodes involvement is considered a contraindication to re-operation. Although we tried to be very accurate in re-staging, three patients presented an advanced stage (two T3N2M0, one T4N2M0) at the pathological examination.
Finally, the time between first resection and tumour recurrence must be taken into consideration. Our results of re-operation for a recurrence performed after a short interval (less than 14 months) are discouraging: no patient survived more than 2 years after the second operation.
On the other hand, the other treatment modalities are of little if any benefit for these patients. In a study of 49 patients treated by radiotherapy for post-resection locally recurrent lung cancer [15] the 3- and 5-year survival rate was both 5%, and the median survival was 11 months. A study on the spread of lung cancer assessed by autopsy in patients who had undergone a pulmonary resection showed that the metastasis are often, and for quite long time, limited to the chest. This means that with a close follow-up we could detect some recurrences at an early stage, making possible a re-operation. We believe that these patients should be seen maximally at 4-months intervals for the first 2 years and 6 months interval thereafter throughout life. At every visit physical examination and chest radiographs should be performed. It is very useful that the last chest radiogram be compared with the oldest one, because only in this way early subtle changes can be detected. We use CT scan to solve question posed by the X-rays.
An increasing number of patients with SPLC are reported in literature. It may be related to the increased incidence of the bronchogenic carcinoma, the increased rate of patients who survive a first pulmonary resection, and the use of developed radiographic techniques, such as computed tomography. The reported incidence is 1–5% in clinical observation [16], but it can be as high as 10–25% in patients who survive more than 3 years after curative resection for lung cancer, emphasizing the fact that most patients will not survive long enough to develop a second primary lung tumour [17]. A study from the Mayo Clinic in 1990 showed an incidence of 1.2% including patients who did not undergo resection and patients in which the SPLC was diagnosed at necropsy [3], while Shields [18] reported an incidence of 1.7% out of 2836. A more recent experience [5] showed an higher incidence (6.3%), probably related to the systematic use of CT scan. Our personal experience includes 20 patients found to have a SPLC during follow-up; these constitute 2% of all patients with resected lung cancer during the last 20 years. The criteria set by Martini et al. [11] in 1975 for defining the methacronous second primary lung cancers have been used by many in the field, even if there is still some controversy regarding the disease-free interval to be used. However, when a methacronous pulmonary lesion is detected, whether with the same cell type (more likely a recurrence) or with different cell type (more likely a SPLC) from the first primary tumour, if it is the only one present in the lung and there is no evidence of extrapulmonary metastasis, it should be always removed. In doing so, a prolonged survival rate can be expected. The reported 5-year survival rate [2–5,13], including our experience ranged from 25 to 52.5% after the second resection for methacronous second cancer, proves the effectiveness of this principle. Whether the new lesion is a primary lung tumour, or a metastasis of the first tumour is only a question of prognosis. We know that prognosis after a second primary lung tumour is better than that after recurrence [3,5], but the treatment plan is basically the same. We only observed a trend toward improved survival in group 2 compared with group 1 without statistical significance. This is probably related to the small number of patients.
Much more debated is the surgical indication for synchronous multiple primary lung tumour, that is related to the difficulty in their diagnostic definition. In these cases the results of surgical therapy are very poor and the patients often die of disseminate disease, indicating that most of these tumour are indeed pulmonary metastasis. Pairolero [19] has proposed to classify these patients in stage IV and has led us to consider for them a conservative treatment or very selective indications to surgery. In our retrospective study we found too few synchronous lung tumours to reach any conclusions.
Regarding the type of surgical treatment, in case of metachronous second primary lung tumour, the wedge resection is a reasonable and safe alternative to the standard resections in the elderly, in patients with poor respiratory reserve and after a pneumonectomy (two cases in our experience). However, the Lung Cancer Study Group [20] showed that resection less extensive than lobectomy places the patient at an increased risk of local recurrence and decreases the chances of long-term survival. Moreover, in almost all articles [2–5] an inferior survival of metachronous second lesions compared with first lesion is reported. This could be related to underestimating of stage because of technical difficulties during the second procedure, but it might be related to employing of more lesser resections. Thus, if the tumour is not peripheral and less than 2 cm in diameter, we consider lobectomy the treatment of choice even for the second resection. In one case we performed a left pneumonectomy after a right upper lobectomy without any postoperative complications; the patient is alive and doing well after 36 months from the second operation. The bronchoplastic procedures are particularly helpful in these type of patients. On the first resection they allow the pulmonary function to be preserved sufficiently for a second lung resection. Moreover, they make possible the resection of a centrally located second primary tumour (two cases in our experience). The second resection can be almost uniformly performed safely, as indicated by our and other morbidity and mortality data [3–5]. Complications occurred in 33% of our patients after the second resection, which is not very different from that previously reported for undergoing pulmonary resection for first lung cancer [21].The overall mortality rate after the second operation for recurrence and SPLC in our study was 7%. Although higher than the overall 3.7% mortality rate reported by the Lung Cancer Study Group [22] for patients undergoing all types of pulmonary resection for the first lung cancer, it was acceptable. At present, we agree with the consideration that cancer recurrence means an insufficient clearing of the tumour, whereas second primary lung tumour suggests a continuous exposure to etiologic risk factor. It is noteworthy that in many reports [2–5] the stage of second new tumour was more advanced than that of the first tumour with a survival rate obviously better for the early stages. Consequently it is imperative to continue surveillance beyond 5 years, and the follow-up intervals are particularly important for detecting a recurrence or a new primary tumour in early stage.
In conclusion, long-term results justify complete work-up of patients with local recurrent and second primary bronchogenic carcinoma. Treatment should be surgical if there is no evidence of distant metastasis and the patient presents an adequate cardio–respiratory reserve. Early detection of second lesion is possible with an aggressive follow-up with resultant prolonged survival.
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Footnotes |
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References |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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