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Ann Thorac Surg 2008;86:921-926. doi:10.1016/j.athoracsur.2008.05.041
© 2008 The Society of Thoracic Surgeons
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Original Articles: General Thoracic

Multiple Lung Cancers Prognosis: What About Histology?

Marc Riquet, MD, PhDa,*, Aurélie Cazes, MD, PhDb, Karel Pfeuty, MDa, Ulrich Davy Ngabou, MDa, Christophe Foucault, MDa, Antoine Dujon, MDd, Eugeniu Banu, MDc

a Department of General Thoracic Surgery, Georges Pompidou European Hospital and Paris Descartes University, Paris, France
b Department of Pathology, Georges Pompidou European Hospital and Paris Descartes University, Paris, France
c Department of Medical Oncology, Georges Pompidou European Hospital and Paris Descartes University, Paris, France
d Cedar Surgical Centre, Boisguillaume, France

Accepted for publication May 15, 2008.

* Address correspondence to Dr Riquet, Thoracic Surgery Department, Georges Pompidou European Hospital, 20 rue Leblanc, Paris, 75015, France (Email: marc.riquet{at}egp.aphp.fr).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 References
 
Background: Among multiple lung cancers (MLC), some may have similar histologic classification. Demonstrating that the second tumor is a metastasis would change the stage and consequently the management. Our purpose was to reconsider this consequence.

Methods: We reviewed 234 patients (194 male and 40 female, from 37 to 83 years of age) with synchronous and metachronous non–small cell MLC. Surgery consisted of a potentially curative complete resection with lymphadenectomy. Patients with similar histologic MLC (considered as metastasis) were compared with those with different histologic classification in terms of MLC chronology, type of resection, pT and pN, stage, and overall survival.

Results: There were 116 metachronous (ipsilateral, n = 48; contralateral, n = 68) and 118 synchronous MLCs (bilateral, n = 10; same lobe, n = 57; other lobe, n = 51). Pneumonectomy was performed in 77 patients, lobectomy in 103, and lesser resection in 54. Histologic classification was similar in 57.9% of patients and different in 42.1%. The 5-year survival rates tended to be lower in patients with synchronous MLCs (23.4% versus 31.6%; p = 0.07). They were higher when synchronous MLCs were located in the same lobe than if they were located in another lobe (29.9% versus 15.6%; p = 0.022). Whatever the type of MLC, the 5-year survival rates were not correlated with similar or different histologic classification.

Conclusions: Our analysis supports that surgery is safe and warranted in MLC patients even if synchronous MLCs present ominously. Changing the staging by establishing the diagnosis of metastasis is probably an important issue warranting further biologic research, but according to our results this diagnosis must not in any case preclude surgery.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 References
 
Multiple lung cancers (MLC) are not uncommon, representing 1.2% to 5.1% of all non–small cell lung cancers (NSCLC) [1–3] and 1.9% to 9% of those NSCLC patients undergoing potentially curative lung resection [3, 4–7]. In the surgical literature, they are most often addressed according to the timing of their discovery, that is metachronous (MMLC) [8–10] or synchronous (SMLC) [11–14]. Whether synchronous or metachronous, their morphology and histology are often similar, which makes it difficult to distinguish a second primary from a metastasis. The criteria introduced by Martini and Melamed [15] can only be applied to MMLC resection or autopsy specimens. It is generally considered, but not demonstrated, that determining the second tumor to be a metastasis would change staging, prognosis, and management. Should it prove correct, more accurate differentiation at the time of biopsy would be clinically useful, and identification techniques requiring little material (DNA studies or other assays such as the p53 gene mutation [16]) would be essential in future reports. By reviewing patients who underwent surgery for SMLCs and MMLCs, our purpose was to look for prognostic differences induced by pathologic disease and histologic classification.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 References
 
Patients
Between January 1983 and December 2005, 3,427 consecutive NSCLC patients underwent surgical resection in two French centers: Georges Pompidou European Hospital, Thoracic Surgery Department, Paris, and Boisguillaume Surgical Center. The surgical procedure was a potentially curative complete resection with systematic hilar and mediastinal lymphadenectomy. Patients who had carcinoid tumors, preoperative neoadjuvant treatments, or palliative surgery were not included in the analysis. Of these 3,427 patients, 731 (21.3%) had a history of a second malignancy, either synchronous or metachronous. This malignancy had a pulmonary origin in 234 patients, who form the basis of this exploratory analysis. Our institutional review board waived obtaining patient consent for this study. Information was obtained from hospital records. There were 194 male and 40 female patients, aged from 37 to 83 years (mean ± standard error of the mean, 63.7 ± 9.1). Adjuvant therapy was performed in 68 patients in a nonrandomized fashion according to specific institutional guidelines adopted by different referring physicians.

Methods
The 234 MLC patients were divided in MMLCs, diagnosed during follow-up, and SMLCs, diagnosed at workup or during surgery. They were compared with the 2,696 patients with lung cancer without prior malignancy (WPMLC). Each group was analyzed and compared with the other group in terms of the following variables: age; sex; anatomic location of the MLC; type of surgical resection; pathologic tumor (pT), nodes (pN), and stage [17]; histology; and overall survival. Metachronous MLCs were further analyzed according to the time interval criterion proposed by Martini and Melamed [15] (inferior or superior at 2 years), and the SMLCs according to their location within lungs (same lobe or other lobe). Both groups of MLCs were also analyzed according to histology: similar histology being considered as potentially metastasis, and different histology as second primary NSCLC.

Follow-up information was obtained either from hospital case records or from a questionnaire completed by the local chest physician or general practitioner or from death certificates. The overall survival defined as the time interval between the date of surgery and the date of death or the last follow-up visit for censored patients was the main outcome. No patient was lost at follow-up. Actuarial survival curves were estimated by the Kaplan–Meier method. Statistical comparisons among survival distributions were made using the log-rank test. Univariate analyses used the following explanatory covariates: age, sex, type of surgical resection, histology, pT and pN status, type of MLC (metachronous or synchronous), and histology (similar or not) between the primary lung cancer and the second one. Hazard ratios with their 95% confidence intervals were estimated using Cox proportional hazards regression analysis. The cutoff probability value used for entering specific explanatory variables into the multivariate analysis was 0.05. The probability values were adjusted according to the multiplicity of tests using the Bonferroni method. Fisher's exact and {chi}2 tests were used to estimate differences between MLC categories on clinical and pathologic variables previously described. All statistical tests were two-sided and assessed for significance at the 0.05 level. The statistical software used for the analysis was SEM (Anticancer Centre Jean Perrin, Clermont-Ferrand, France) [18].


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 References
 
There were 116 MMLCs and 118 SMLCs. Mean age was 64.2 ± 7.9 years (range, 44 to 80 years) for MMLC and 63.2 ± 10 years (range, 37 to 83 years) for SMLC, and sex distribution was 102 males (88.7%) for MMLC and 92 males (77.9%) for SMLC. Metachronous MLCs occurred in the ipsilateral lung in 48 patients (41.4%) and in the contralateral lung in 68 (58.6%). Synchronous MLCs were bilateral in 10 patients and ipsilateral in 108: 57 were located in the same lobe and 51 in another lobe.

The type of resection for MMLC and SMLC patients was as follows: segmentectomy or wedge, 35 (30.2%) and 19 (16.1%); lobectomy 45 (38.8%) and 58 (49.2%); completion pneumonectomy or pneumonectomy 36 (31.0%) and 41 (34.7%), respectively (36 completion pneumonectomies were performed in MMLC patients). Postoperative complications were observed in 28.2% of patients (n = 66; 20 deaths were registered). Postoperative complications and mortality rates were 36.2% (42 of 116) and 12.8% (14 of 116) for MMLC, and 28.8% (34 of 118) and 5% (6 of 118) for SMLC, respectively.

Details of resections in MLCs subgroups are given in Table 1. Five-year survival rates after major resections were not different from those after lesser resections, whatever the N status (Fig 1). A major resection (pneumonectomy or completion pneumonectomy) was more frequently required in case of pN1 and pN2 involvement (44 of 77 versus 46 of 147; p = 0.00018).


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  		Table 1 Type of Resection of Multiple Lung Cancers According to the Location of the Tumors and N Status
 

Figure 1
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  		Fig 1. Survival according to the type of resection (pneumonectomy with completion [curve 1], lesser resection [curve 2]). When postoperative deaths were excluded, difference between survival rates was not statistically significant anymore (34.1% and 36.4%, respectively; p = 0.10).

 
Pathology characteristics and stages of MLCs are given in Table 2: pT1 and pN0 were significantly more frequent in MMLC, and pN2 was more frequent among SMLC patients. Adenocarcinomas were more frequent in SMLC than in MMLC and WPMLC. Prognosis appeared poorer in SMLC patients than in MMLC or WPMLC patients (Fig 2). Survival rates among the three groups were also different in the case of pN0 patients (Fig 3). The histologic classification of the first NSCLC tumor was not available in 1 MMLC patient. The MLC histologic classification was similar in 57.9% of patients (135 of 233) and different in 42.1% (98 of 233). Details of the histologic classification are shown in Table 3. Histologic classification was similar in 61.3% of the adenocarcinomas (73 of 119), in 71.2% of the squamous cell carcinomas (57 of 80), and in 14.3% (5 of 35) of the miscellaneous carcinomas (including adenosquamous, undifferentiated large cell, neuroendocrine large cell, and other rare carcinomas). The 5-year survival rates were not different depending on whether the histologic classification was similar or different (Table 3).


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  		Table 2 Pathology Characteristics and Stages of Multiple Lung Cancers
 

Figure 2
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  		Fig 2. Survival of lung cancer patients without prior malignancy (curve 3), lung cancer patients with multiple metachronous tumors (curve 2), and lung cancer patients with multiple synchronous tumors (curve 1).

 

Figure 3
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  		Fig 3. Survival of lung cancer patients without lymph node involvement (N0) with either no prior malignancy (curve 3), multiple metachronous tumors (curve 2), or multiple synchronous tumors (curve 1).

 

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  		Table 3 Histology Pattern According to the Multiple Lung Cancer Category and Lymph Node Status (N0, N1, N2)
 
Results concerning SMLCs are shown in Table 4. The N2 (mediastinal) involvement was more frequent when SMLCs were located in another lobe, and when MLC histologic classification was different (60.9% versus 31.3%; p = 0.029). The 5-year survival rates were better when the SMLCs were located in the same lobe rather than in another ipsilateral lobe (29.9% versus 15.6%; p = 0.022). However, survival rates between stage IIIB SMLC and stage IIIB WPMLC were not different (30.3% versus 27.4%; p = 0.37); survival rates between stage IV SMLC and stage IIIB WPMLC were also not different despite a tendency to a poorer outcome for stage IV SMLC patients (15.5% versus 27.4%; p = 0.20). Multiple lung cancer histologic classification, either different or similar, was not a factor of prognosis in SMLC patients. Multiple lung cancers with more than two nodules were observed in 14 patients, always SMLC patients (13.1%). Histologic classification was similar in 64% (9 of 14) of cases. Five-year survival rates reached 40% and were not modified by the similarity or not of histologic classification.


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  		Table 4 Histology Pattern According to the Synchronous Multiple Lung Cancer Anatomic Location Within the Lung and the Lymph Node Status (N) a
 
Results concerning MMLCs are given in Table 5. Different MLC histologic classification tended to be more frequent and 5-year survival rates to be higher after a 2-year interval (not significant). No result depended on histologic classification.


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  		Table 5 Metachronous Multiple Lung Cancer a
 
Multivariate analysis indicated that the only significant factors related with prognosis were age and N2 (p = 0.006 and 0.0000005, respectively).


   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
References
 
Multiple lung cancers represent less than 6% of NSCLC patients [2–7], but 44% of MLC patients are clinically operable [1], and rates of operability reach 68.4% [2] and 76.5% [4] in surgical series. Metachronous MLCs and SMLCs have different clinical presentation. Metachronous MLCs are observed during follow-up in 7.7% of patients with T1 or T2 and N0 or N1 resected NSCLC: 5.5% occurring in the ipsilateral and 2.2% in the contralateral lung. They represent 21.8% of all diagnosed recurrences [19]. Synchronous MLCs represent 19.6% to 40% of MLC patients [2–4, 6, 20], sometimes almost half of patients [5, 7] as in our study. They may affect about 69.8% of patients [11] when including tumors discovered within a 24-month delay, provided that they were retrospectively present at the time of the treatment of the first tumor (by reviewing the imaging files). Synchronous MLCs are rarely diagnosed before surgery, 13.7% and 18.7% according to Okumura and associates [12] and Nakawaga and colleagues [13], which may account for the higher rates of operability, ranging from 67.8% [21] to 95.5% of patients [22], respectively.

The histologic classification of MLCs was similar in 57.9% of patients, a frequency slightly above literature data (50.8% [3] and 54.9% [6]). However, there is an important discrepancy in the literature when considering both groups of MLCs. Histologic classification is similar in 25% to 72.2% of SMLC patients [2, 4, 5, 7, 20, 21] and in 34.4% to 70.5% of MMLC patients [2, 4, 5, 7, 9, 10, 22], respectively. To have a better idea of the histology patterns, we added up the figures reported in these references: histologic classification was similar in 54.15% of MLC patients (300 of 554), 49.3% in case of SMLCs (70 of 142) and 57.1% in case of MMLCs (169 of 296). These results approaching ours illustrate that MLCs may be considered as metastases in more than half of patients. Synchronous MLCs are composed of different groups according to their anatomic location. Most of them are located in the ipsilateral lung, with a frequency ranging from 64.6% to 95.3% of patients [5, 11, 13, 22], which is similar with our data and probably related to the fact that most SMLCs are diagnosed during or after surgery [12, 13]. Ferguson and colleagues [21] observed a lower frequency (39.3%), but the MLCs were diagnosed before surgery in 23 of 28 patients. The incidence of SMLCs located in the same lobe ranges from 0% [20] to 86.8% [12]. In our series, they formed 52.3% of SMLC patients (n = 56; stage IIIB in Mountain's classification [17]).

The overall 5-year survival rates are commonly found to be between 23.4% and 37% for MMLC patients [2–5, 8–10], and between 0% to 20% for SMLC patients [2, 3, 6, 20]. This is in agreement with our results. The prognosis of SMLC, classified as either stage IIIB or stage IV, was not different from that of WPMLC classified as stage IIIB, which supports the proposal of classifying synchronous nodules as stage III in the IASLC lung cancer staging project [23]. Although our survival rates were slightly higher than 20%, the prognosis of the SMLC patients was significantly poorer than that of the MMLC patients. The main explanation for this difference was the frequency of involved lymph nodes among the SMLC patients. The survival rates were no longer any different when comparison was performed in the same pathologic N subgroups, which was also mentioned by Deschamps and colleagues [2]. Lymph node involvement was the main prognostic factor, which also appeared obvious in other reports concerning SMLCs [11, 13, 21].

Whether these lesions are metastases or not, our study tends to demonstrate that the prognosis is not related to histologic classification, which is also demonstrated by most authors [2, 4, 8, 10, 11, 20, 21]. However, Doddoli and colleagues [9] reported a tendency to a poorer outcome in patients with similar MMLC histologic classification when the time interval between surgery and the apparition of the first tumor was less than 2 years, and Aziz and colleagues [6] showed that patients with different MMLC histologic classification had a better prognosis. In their study, the 5-year survival rates were 51% in case of different histologic classification and 31% in case of similar histologic classification, which however is a good result for tumors that may be considered as metastases.

The 5-year survival rates of SMLC patients are higher when tumors are located in both lungs, which may be explained by a more selected lymph node disease-free subset of patients. Survival rates are better for SMLCs located in the same lobe than for those located in another ipsilateral lobe, which was also observed by Trousse and colleagues [11]. This difference may be related to more frequent N2 involvement and required pneumonectomy in the latter: the extent of the disease being also a reason that explained the lesser frequency of other surgical procedures. In our series, the SMLC patients with more than two nodules (13.1%) showed 5-year survival rates reaching 40% despite similar histologic classification in 64% of cases, a good result for MLCs more likely to be considered as metastases. In the literature, the frequency of those patients with three or more nodules ranges from 3.4% to 16.9% [2, 3, 11, 22]. Half of patients studied by Deschamps and colleagues [2] were also long survivors.

Deschamps and colleagues [2] stressed that an aggressive surgical approach is safe and warranted in most patients with MLCs even if the presence of SMLCs is ominous. This is supported by our study whether MLC are considered as second primary or as metastasis. In addition, Fukuse and colleagues [22] reported that patients with MLCs considered as metastases showed a significantly better prognosis compared with those with other organ, distant metastases. Changing the staging of the tumor and therefore its management by determining whether the second tumor represents a true independent primary or a metastasis is probably an important issue warranting further biologic research, but further surgical studies including MLC in genetic determination assays would be useful to precisely define potential subgroups with poorer prognosis. Regarding the relatively good prognosis encountered whatever the suspected nature, metastatic or not, of the second tumor, surgery actually still has to be seriously considered to manage this particular MLC entity.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 

  1. Razzuk MA, Pockey M, Urschel HC, Paulson HC. Dual primary bronchogenic carcinoma Ann Thorac Surg 1974;17:425-433.[Medline]
  2. Deschamps C, Pairolero PC, Trastek VF, Payne WS. Multiple primary lung cancers J Thorac Cardiovasc Surg 1990;99:769-778.[Abstract]
  3. Antakli T, Schaefer RF, Rutherford JE, Read RC. Second primary lung cancer Ann Thorac Surg 1995;59:863-867.[Abstract/Free Full Text]
  4. Adebonojo SA, Moritz DM, Danby CA. The results of modern surgical therapy for multiple primary lung cancers Chest 1997;112:693-701.[Medline]
  5. Okada M, Tsubota N, Yoshimura M, Miyamoto Y. Operative approach for multiple primary lung carcinomas J Thorac Cardiovasc Surg 1998;115:836-840.[Abstract/Free Full Text]
  6. Aziz TM, Saad RA, Glasser J, Jilaihawi AN, Prakash D. The management of second primary lung cancers. A single centre experience in 15 years. Eur J Cardiothorac Surg 2002;21:527-533.[Abstract/Free Full Text]
  7. Tsunezuka Y, Matsumoto I, Tamura M, et al. The results of therapy for bilateral multiple primary lung cancers: 30 years experience in a single centre Eur J Surg Oncol 2004;30:781-785.[Medline]
  8. van Rens MTM, Zanen P, Brutel de la Riviére A, Elbers HRJ, van Sureters HA, van den Bosh JMM. Survival after resection of metachronous non-small cell lung cancer in 127 patients Ann Thorac Surg 2001;71:309-313.[Abstract/Free Full Text]
  9. Doddoli O, Thomas P, Ghez O, Giudicelli R, Fuentes P. Surgical management of metachronous bronchial carcinomas Eur J Cardiothorac Surg 2001;19:899-903.[Abstract/Free Full Text]
  10. Battafarano RJ, Force SD, Meyers BF, et al. Benefits of resection for metachronous lung cancer J Thorac Cardiovasc Surg 2004;127:836-842.[Abstract/Free Full Text]
  11. Trousse D, Barlesi F, Loundou A, et al. Synchronous multiple primary lung cancers: an increasing clinical occurrence requiring multidisciplinary management J Thorac Cardiovasc Surg 2007;133:1193-1200.[Abstract/Free Full Text]
  12. Okumura T, Asamura H, Suzuki K, Kondo H, Tsuchiya R. Intrapulmonary metastasis of non-small cell lung cancer: a prognostic assessment J Thorac Cardiovasc Surg 2001;12:24-28.
  13. Nakagawa T, Okumura N, Miyushi K, Matsuka T, Kameyana K. Prognostic factors in patients with ipsilateral pulmonary metastasis from non-small cell lung cancer Eur J Cardiothorac Surg 2005;28:635-639.[Abstract/Free Full Text]
  14. Rostad H, Strand T-E, Naalsund A, Norstein J. Resected synchronous primary lung tumors: a population-based study Ann Thorac Surg 2008;85:204-210.[Abstract/Free Full Text]
  15. Martini N, Melamed MR. Multiple primary lung cancer J Thorac Cardiovasc Surg 1975;70:606-612.[Abstract]
  16. Matsuzoe D, Hideshima T, Ohshima K, Kawahara K, Shirakusa T, Kimura A. Discrimination of double primary lung cancer from intrapulmonary metastasis by p53 gene mutation Br J Cancer 1999;79:1549-1552.[Medline]
  17. Mountain CF. Revisions in the International System for Staging Lung Cancer Chest 1997;111:1710-1717.[Medline]
  18. Kwiatkowski F. SEM (Statistiques, Epidémiologie, Médecine): un outil de gestion informatique et statistique adapté à la recherche en cancérologie Bull Cancer 2000;87:715-721.[Medline]
  19. Auerbach O, Stout AP, Hammond EC, Garfinkel L. Multiple primary bronchial carcinomas Cancer 1967;20:699-705.[Medline]
  20. Rea F, Zuin A, Callegaro D, Bortolotti L, Guanella G, Sartori F. Surgical results for multiple primary lung cancers Eur J Cardiothoracic Surg 2001;20:489-495.[Abstract/Free Full Text]
  21. Ferguson MK, DeMeester TR, Deslauriers J, Little AG, Piraux M, Golomb H. Diagnosis and management of synchronous lung cancers J Thorac Cardiovasc Surg 1985;89:378-385.[Abstract]
  22. Fukuse T, Hirata T, Tanaka F, Yanagihara K, Hitomi S, Wada H. Prognosis of ipsilateral intrapulmonary metastases in resected nonsmall cell lung cancer Eur J Cardiothorac Surg 1997;12:218-223.[Abstract]
  23. Goldstraw P, Crowly J, Charsky K, et al. The IASLC Lung Cancer Staging Project: Proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of Malignant Tumours J Thorac Oncol 2007;2:706-714.[Medline]



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