Ann Thorac Surg 1999;67:548-549
© 1999 The Society of Thoracic Surgeons
Case Reports
Metachronous cancers or late recurrences after resection of stage I lung cancer
Roberta Lenner, MDa,
Alvin S. Teirstein, MDa,
Daniel J. Krellenstein, MDa
a Division of Pulmonary and Critical Care Medicine, Mount Sinai Medical Center, New York, New York, USA
Accepted for publication July 29, 1998.
Address reprint requests to Dr Lenner, Mount Sinai Medical Center, Box 1232 One Gustave L. Levy Place, New York, NY 10029
e-mail: egandrobi{at}aol.com
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Abstract
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In 2 patients with stage I lung cancer, tumors recurred at their resection lines 10 years after the original surgical resections. These cases suggest that the prognosis of late cancer occurrences after resected primary lung malignancies might be related to the interval of time between primary and subsequent cancers rather than to their categorization as recurrent or metachronous cancers.
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Introduction
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Non–small-cell lung cancer (NSCLC) is the most common lethal cancer in the United States [1]. Although stage I lung cancer has the best prognosis, 20% to 40% of these tumors will not be eliminated surgically mostly because of distant metastases [2–4]. Locoregional recurrences are defined as tumor of the same histopathologic type in the ipsilateral hemithorax within 5 years of resection of the original cancer [2, 4]. Controversy exists regarding the time frame that would distinguish local recurrence from a new metachronous primary cancer of the same histopathologic type. According to most current criteria, cancer that occurs 5 years after the original lung primary neoplasm is classified as a new metachronous cancer [3, 5–7]. Metachronous lung cancers have a better prognosis than recurrent disease [2, 4, 6–8]. However, some of these late metachronous cancers might not be new primary lesions but recurrences of the original cancers with a very long doubling time. We report 2 patients with stage I lung cancer that recurred at the resection line 10 years after the original surgical resections. The course of these patients suggests that the current practice, which differentiates between tumor recurrence and metachronous lung cancer by disease-free interval might not be valid.
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Patient 1
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A 60-year-old woman had a 3-cm nodule in the posterior segment of the right upper lobe on a chest roentgenogram. Transbronchial biopsy results indicated that the tumor was a mucin-secreting adenocarcinoma. Mediastinoscopy showed no metastatic disease. The patient underwent a right upper lobe lobectomy in May 1983. The patient was followed up closely afterwards and in June 1986 a new lingular nodule was noted on a chest radiograph. Results of a search for metastatic disease were negative. Because of limited pulmonary function the patient underwent a wedge resection. Pathologic analysis disclosed a 1-cm well-differentiated adenocarcinoma, different in histologic appearance than the one diagnosed 3 years earlier. The surgical margins were free of tumor.
In February 1997, 128 months after her second thoracotomy, a nodule was noted on a routine chest radiograph in the lingula, in the area of the previous wedge resection. Tests for metastatic disease were negative. The new nodule was removed by wedge resection and revealed a 2.5 x 2-cm tumor located within the scar of the previous wedge resection. Pathologic analysis disclosed a well-differentiated adenocarcinoma, identical with the lesion previously removed by wedge resection more than 10 years previously. All lymph nodes were negative for metastatic disease.
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Patient 2
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A 56-year-old man had a peripheral nodule on chest roentgenogram in November 1986. Computed tomography of the head and bone scan were negative for meta
static disease. In December 1986 he underwent a right middle lobe lobectomy. Pathologic analysis disclosed a 2.5-cm, well-differentiated adenocarcinoma. The surgical margins were free of tumor. The patient was followed up at regular intervals. In November 1996, two new nodules appeared on routine chest radiograph adjacent to the line of surgical sutures. Computed tomography of the head and bone scan were normal. Thoracotomy was performed revealing two nodules: a 2.5 x 1.5 x 1.5-cm nodule was located directly in the previous suture line, and a 1 x 1 x 0.8-cm nodule in close proximity, in the lower lobe. All 17 hilar lymph nodes were negative for tumor involvement. The patient underwent a completion right pneumonectomy. Pathologic analysis disclosed a well-differentiated adenocarcinoma in both nodules, identical to the tumor resected 10 years earlier.
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Comment
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When a patient presents with a prolonged interval between resection of a primary lung cancer and appearance of a second tumor, late recurrence is difficult to differentiate from a second primary lung cancer. Most investigators today use the criteria for metachronous cancers that were established by Martini and Melamed in 1975 [3]: - Different histologic characteristics
- If histologic characteristics are the same, then
- Disease-free interval between cancers at least 2 years or
- Origin from cancer in situ or
- Second cancer in different lobe but no cancer in common lymphatics or extrapulmonary metastasis at time of diagnosis.
By these criteria, the 2 patients described here would have metachronous primary cancers. Yet, because the cancers had the same histopathologic features of the original tumors and they recurred at the margins of the original resection, we believe that they represent local recurrences. Since we do not have a diagnostic tool that would serve as the gold standard in distinguishing tumor recurrence from new primary cancer, the sensitivity and specificity of the above criteria are unknown. Moreover, each of these criteria is subject to criticism. The histologic heterogeneity of lung cancers may render the diagnosis of a new primary lung cancer based on different histologic characteristics unreliable. Although most lung cancer recurrences happen in the first 2 years after surgical removal, 10% of all tumor recurrences appear 5 years or longer after the initial resection [2].
It is possible that these 2 patients had new primary scar carcinomas. In both of them the cancer recurred in close proximity to the scar of a previous resection. However, the tumors themselves did not contain scar tissue in the pathologic specimen. It is possible that the presumed recurrent tumors in our patients developed from one or more cancer cells with very long doubling times that were left behind at the time of the original resection or that their growth was arrested transiently by a hormonal or immunologic mechanism. It is possible that the same process can occur from micrometastatic tumor cells within different parts of the lung. Most previous studies of the behavior of metachronous primary cancers were retrospective, used different definitions, and involved small numbers of patients [4, 5, 7, 8]. Furthermore, follow-up times varied from study to study. The incidence of metachronous lung cancer after complete surgical resection of a stage I lung cancer in these studies ranged from less than 1% to 10% to 15% [1–3]. True metachronous primary cancers have a better prognosis than those of recurrent disease (5-year survival, 23% to 50% versus 11%) [2, 4, 6–8]. Late recurrent cancers, however, include tumors that have long doubling times and have an inherently good prognosis. If these patients were classified as having metachronous lung cancer, it would have improved the survival statistics of the later type of tumor and may explain in part the observation of Rosengart and associates [6], who noted significantly better survival of patients with late metachronous cancers as opposed to early metachronous cancers. Perhaps the prognosis is directly related to the duration of the interval between the primary and the secondary cancers, regardless of whether the latter represents a metachronous primary tumor or recurrence of the original cancer. With the advent of DNA analysis, it might be possible to determine accurately the specific relationship between the primary and secondary lesions, as well as their clinical significance.
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References
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Abstract
Introduction
