Ann Thorac Surg 2007;83:397-400
© 2007 The Society of Thoracic Surgeons
Original Articles: General Thoracic
Surgical Resection for Multifocal (T4) Non-Small Cell Lung Cancer: Is the T4 Designation Valid?
Jeffrey L. Port, MD,
Robert J. Korst, MD,
Paul C. Lee, MD,
Amanda L. Kansler, MPH,
Yaniv Kerem, BA,
Nasser K. Altorki, MD*
Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Weill Medical College of Cornell University, New York
Accepted for publication August 10, 2006.
* Address correspondence to Dr Altorki, Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Suite M404, New York Presbyterian Hospital–Weill Medical College of Cornell University, 525 E 68th St, New York, NY 10021. (Email: nkaltork{at}med.cornell.edu).
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Abstract
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BACKGROUND: The current international staging system for lung cancer designates intralobar satellites as T4 disease. In this study, we sought to determine the impact of multifocal, intralobar non-small cell lung cancer (NSCLC) on patient survival and its potential relevance to stage designation.
METHODS: We conducted a retrospective review of our thoracic surgical cancer registry from 1990 to 2005. Included were 53 patients with a resected lung cancer containing intralobar satellites detected preoperatively (n = 8) or in the resected specimen (n = 45). Patients with multicentric bronchioloalveolar cancer were excluded. All patients had an anatomic resection with mediastinal lymph node dissection. Median follow-up for the entire group was 31 months. Survival was calculated by the Kaplan-Meier method. A Cox proportional hazards regression model was performed to examine simultaneously the effects on overall survival of age, gender, nodal disease, number of satellite lesions, lymphatic invasion, and T status.
RESULTS: The median age of the 53 patients with multifocal, intralobar (T4) disease was 68 years and 31 were women. Ten patients had more than one satellite lesion. Overall 5-year survival was 47.6% (95% confidence interval [CI], 27.36% to 65.30%) for all patients with resected intralobar satellites. Patients without nodal metastases had a 5-year survival of 58.4% (95% CI, 28.76% to 79.30%). The Cox regression identified female gender (adjusted hazard ratio [HR], 0.31; 95% CI, 0.10 to 0.96; p < 0.04) as a significant prognostic variable but only a trend towards significance for nodal status (adjusted HR, 2.3; 95% CI, .83 to 6.26; p < 0.11).
CONCLUSIONS: Patients with intralobar multifocal NSCLC detected in the resected specimen have a more favorable prognosis after surgical resection than might be predicted by their stage T4 designation. Five-year survival rates, especially in T4N0 patients, more closely approximate those with stages IB or II NSCLC.
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Introduction
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The staging and treatment of multifocal lung cancer is controversial [1–10], mainly because currently, there is no clear mechanism to establish monoclonality, and the distinction of multiple primary lung carcinomas from intrapulmonary metastases is determined solely by clinical and histopathologic criteria. In 1997, the Union Internationale Contre le Cancer and the American Joint Committee on Cancer revised the TNM staging system and designated multiple lesions within the same lobe as T4 disease and lesions in all other lobes as M1 disease [11].
Although several reports have focused on patients with multifocal bronchioloalveolar carcinoma (BAC), a known favorable subtype, little is known about the ideal management of patients with synchronous, intralobar, multifocal, non-BAC tumors [12–15]. The current analysis was initiated to examine the hypothesis that patients with primary NSCLC and intralobar satellites have a more favorable prognosis after surgical resection than that implied by their T4 designation.
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Patients and Methods
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We conducted a retrospective review of all patients with multifocal, intralobar NSCLC who were surgically treated at our institution between January 1990 and December 2004. Patients with intralobar (T4) disease that was identified on the preoperative computed tomography (CT) scan report or in the pathology report were included. Intrapulmonary satellites were defined as independent lesions separate from the primary tumor and usually smaller, yet having the same histopathologic features as the primary lesion. Pathologic type, stage, and the presence of lymphovascular invasion were assessed.
Only patients who underwent a complete resection with curative intent were included. Patients with a second primary tumor were excluded. All patients underwent a complete mediastinal lymph node dissection. We excluded patients with multifocal BAC, disparate histologies in the primary versus the satellite lesions, and patients who underwent resection after neoadjuvant therapy. In addition, patients with pure ground glass opacities on preoperative CT scan were excluded. Hospital and office records were examined for demographic and pathologic data, including age, gender, surgical procedure, histology, lymphovascular invasion, tumor size, and multiplicity.
Survival was calculated by the Kaplan-Meier method. A Cox proportional hazards regression model was performed to examine simultaneously the effects on overall survival of age, nodal disease, number of satellite lesions, lymphatic invasion, and T status of the index lesion. The effect of each variable in the model was evaluated with the use of the Wald test and expressed by the hazards ratio (HR) with a 95% confidence interval (CI). The study was approved by the Institutional Review Board of Weill Medical College of Cornell University. Individual patient consent was waived.
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Results
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Fifty-three patients (31 women) with a median age of 68 years were identified from our prospectively assembled thoracic cancer registry (Table 1). Multifocal disease was predicted preoperatively on CT scanning in 8 patients and incidentally noted in the final pathology report in 45. All patients underwent an anatomic resection. The types of resection are summarized in Table 1. An R0 resection was performed in all 53 patients. Almost all of the patients (n = 45) had an adenocarcinoma (Table 1), and 35 had node-negative disease. Median follow-up time was 31 months.
Overall 5-year survival for all resected patients with intralobar satellites was 47.6% (95% CI, 27.36 to 65.30), with a median survival of 44 months (Fig 1). There was a trend towards an improved 5-year survival for node-negative patients (58.4%; 95% CI, 27.36% to 65.30%; p = 0.06; Fig 2). Lymphovascular invasion was identified in 16 patients and did not appear to negatively impact survival (Fig 3). The finding that 43 patients had more than one satellite in the resected lobe did not appear to impact overall survival (Fig 4). When the pathologic stages were analyzed without reference to the satellite lesions, there appeared to be differences in survival for IA patients versus all other stages (Figs 5, 6).
The Cox regression identified female gender (adjusted HR, 0.31; 95% CI, .10 to .96; p < 0.04) as an important prognostic variable but only a trend towards significance for nodal status (adjusted HR, 2.3; 95% CI, .83 to 6.26; p < 0.11).
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Fig 6. Overall survival based on the primary lesion’s original T status for IA versus all other stages.
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Comment
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Clearly, the most important indicator of survival in lung cancer patients is the TNM stage. Most often the stage is easily arrived at by routine preoperative assessment and appropriate pathologic evaluation. However, in the situation where multiple neoplasms are detected in the same lobe or in an adjacent lobe, confusion can arise about whether these additional lesions represent metastases, multicentric synchronous disease, or even a benign process [16, 17].
An estimated 16% of potentially operable patients with stages I to III NSCLC will have additional pulmonary nodules identified on their preoperative CT scan, most of which will represent benign disease [18]. It is important, therefore, not to make clinical judgments in these cases based solely on the radiographic appearance without tissue confirmation. Also, in most cases multifocality will not be apparent preoperatively during clinical staging. Only 15% of patients in our study were identified preoperatively with T4 multifocal disease. Most T4 patients, therefore, will be identified either intraoperatively or after a complete pathologic examination of the resected specimen is completed.
There is considerable controversy related to the diagnosis, treatment, and long-term survival of these patients. The current staging system regards multiple intralobar sites of disease as T4 and extralobar sites as M1 disease [11]. The inherent implication of the current staging system is that patients with multifocal intralobar disease may not benefit from primary resection. Several small series have demonstrated variable results after surgical resection. Some of the confusion may be related to the inclusion of multifocal BACs in some analyses, an entity with a known favorable outcome [3].
The current analysis reviews our experience with completely resected, intralobar multifocal disease excluding BAC lesions. All patients underwent an anatomic resection with a complete mediastinal lymph node dissection. The overall 5-year survival of 47.6% (95% CI, 27.36% to 65.30%) compares favorably with previous reports and highlights the obvious survival differences with other IIIB patients [6, 8, 9]. Node-negative patients had a 5-year survival of 58.4% (95% CI, 27.36% to 65.30%), which approached significance compared with node-positive patients. Although others have reported a decrease in survival related to the presence of lymphovascular invasion, none was apparent from our analysis [4].
Interestingly, most patients had more than one satellite lesion present in the resected lobe, which did not appear to decrease survival in comparison to patients with an isolated satellite lesion (Fig 4). When the pathologic T and N status were assigned to patients disregarding the associated satellite lesion, stage 1A patients had an improved survival compared with all other stages (Fig 6). Although differences were discernible between other stages, they did not reach statistical significance (Fig 5). Perhaps, with larger numbers, the survival differences may have been significantly different.
If these results are substantiated by other studies, it is possible that the staging of NSCLC with intralobar satellites may be determined by the TNM status of the index lesion. Although this study is limited by its retrospective nature and the small number of patients studied, our results suggest that the current TNM designation of intralobar satellites as T4 disease may be inappropriate and does not reflect the favorable prognosis of this subset of patients compared with other stage groupings within stage IIIB.
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References
|
|---|
- Carey FA, Donnelly SC, Walker WS, Cameron EW, Lamb D. Synchronous primary lung cancers: prevalence in surgical material and clinical implications Thorax 1993;48:344-346.[Abstract/Free Full Text]
- Ferguson MK. Synchronous primary lung cancers Chest 1993;103:398S-400S.[Medline]
- Battafarano RJ, Meyers BF, Guthrie TJ, Cooper JD, Patterson GA. Surgical resection of multifocal non-small cell lung cancer is associated with prolonged survival Ann Thorac Surg 2002;74:988-989.[Abstract/Free Full Text]
- Nakajima J, Furuse A, Oka T, Kohno T, Ohtsuka T. Excellent survival in a subgroup of patients with intrapulmonary metastasis of lung cancer Ann Thorac Surg 1996;61:158-162.[Abstract/Free Full Text]
- Vansteenkiste JF, De Belie B, Deneffe GJ, et al. Practical approach to patients presenting with multiple synchronous suspect lung lesions: a reflection on the current TNM classification based on 54 cases with complete follow-up Lung Cancer 2001;34:169-175.[Medline]
- Yoshino I, Nakanishi R, Osaki T, et al. Postoperative prognosis in patients with non-small cell lung cancer with synchronous ipsilateral intrapulmonary metastasis. Ann Thorac Surg 199;64:809–13.
- Adebonojo SA, Moritz DM, Danby CA. The results of modern surgical therapy for multiple primary lung cancers Chest 1997;112:693-701.[Medline]
- Okada M, Tsubota N, Yoshimura M, Miyamoto Y, Nakai R. Evaluation of TMN classification for lung carcinoma with ipsilateral intrapulmonary metastasis Ann Thorac Surg 1999;68:326-330.[Abstract/Free Full Text]
- Shimizu S, Yatabe Y, Koshikawa T, et al. High frequency of clonally related tumors in cases of multiple synchronous lung cancers as revealed by molecular diagnosis Clin Cancer Res 2000;6:3994-3999.[Abstract/Free Full Text]
- Verhagen AF, Tavilla G, van de Wal HJ, et al. Multiple primary lung cancers Thorac Cardiovasc Surg 1994;42:40-44.[Medline]
- Mountain CF. Revisions in the International System for Staging Lung Cancer Chest 1997;111:1710-1717.[Medline]
- Rea F, Zuin A, Callegaro D, Bortolotti L, et al. Surgical results for multiple primary lung cancers Eur J Cardiothorac Surg 2001;20:489-495.[Abstract/Free Full Text]
- Roberts PF, Straznicka M, Lara PN, et al. Resection of multifocal non-small cell lung cancer when the bronchioloalveolar subtype is involved J Thorac Cardiovasc Surg 2003;126:1597-1602.[Abstract/Free Full Text]
- Nakata M, Sawada S, Yamashita M, et al. Surgical treatments for multiple primary adenocarcinomas of the lung Ann Thorac Surg 2004;78:1194-1199.[Abstract/Free Full Text]
- Deslauriers J, Brisson J, Cartier R, et al. Carcinoma of the lungEvaluation of satellite nodules as a factor influencing prognosis after resection. J Thorac Cardiovasc Surg 1989;97:504-512.[Abstract]
- Hiroshima K, Toyozaki T, Kohno H, Ohwada H, Fujisawa T. Synchronous and metachronous lung carcinomas: molecular evidence for multicentricity Pathol Int 1998;48:869-876.[Medline]
- Pommier RF, Vetto JT, Lee JT, Johnston KM. Synchronous non-small cell lung cancers Am J Surg 1996;171:521-524.[Medline]
- Keogan MT, Tung KT, Kaplan DK, et al. The significance of pulmonary nodules detected on CT staging for lung cancer Clin Radiol 1993;48:94-96.[Medline]
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Abstract
Introduction
