Surgical treatment of metachronous second primary lung cancer after complete resection of non-small cell lung cancer

Masatsugu Hamaji; Mark S. Allen; Stephen D. Cassivi; Claude Deschamps; Francis C. Nichols; Dennis A. Wigle; K. Robert Shen

doi:10.1016/j.jtcvs.2012.12.051

Surgical treatment of metachronous second primary lung cancer after complete resection of non-small cell lung cancer

Masatsugu Hamaji, Mark S. Allen, Stephen D. Cassivi, Claude Deschamps, Francis C. Nichols, Dennis A. Wigle, K. Robert Shen

Research output: Contribution to journal › Article › peer-review

64 Scopus citations

Abstract

Objective: To clarify the perioperative and oncologic outcome of pulmonary resection for a metachronous second primary lung cancer (MSPLC) following resection of an initial non-small cell lung cancer (NSCLC). Methods: Retrospective chart review identified 161 patients (88 men and 73 women) with a median age of 70 years (range, 34-88 years) who underwent pulmonary resection for MSPLC between January 2000 and December 2009. Operative morbidity, mortality, and relevant factors were analyzed with χ² test or Fisher exact test and Mann-Whitney U test. Survival was analyzed with Kaplan-Meier and Cox proportional hazard method. Results: The median interval between the initial and subsequent resection for MSPLC was 42.7 months (range, 7-205 months). There was no operative mortality and postoperative complication rate was 29%. In multivariate analysis, ipsilateral operation (P = .0002) and a lower predicted preoperative percent forced expiratory volume in the first second (P = .0035) were significant risk factors for postoperative complications. Five-year overall survival rates after resection of the initial and second metachronous NSCLC were 87.4% and 60.8%, respectively. Significant negative long-term prognostic factors for survival following resection of a MSPLC in multivariate analysis were tumor size >2 cm (P = .003) and number of pack years of smoking (P = .005). Metastatic nodal disease (P = .19) or a sublobar resection (P = .17) were not associated with worse survival. Conclusions: Surgical treatment of a MSPLC can be undertaken with 5-year survival rate of 60%. Expected operative morbidity and mortality are comparable to primary surgery. Tumors 2 cm or smaller are associated with improved survival and freedom from recurrence. Close long-term follow-up of patients who have undergone resection of NSCLC is recommended.

Original language	English (US)
Pages (from-to)	683-691
Number of pages	9
Journal	Journal of Thoracic and Cardiovascular Surgery
Volume	145
Issue number	3
DOIs	https://doi.org/10.1016/j.jtcvs.2012.12.051
State	Published - Mar 2013

ASJC Scopus subject areas

Surgery
Pulmonary and Respiratory Medicine
Cardiology and Cardiovascular Medicine

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10.1016/j.jtcvs.2012.12.051

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@article{befe4a120d694b698048a198cbe375f2,

title = "Surgical treatment of metachronous second primary lung cancer after complete resection of non-small cell lung cancer",

abstract = "Objective: To clarify the perioperative and oncologic outcome of pulmonary resection for a metachronous second primary lung cancer (MSPLC) following resection of an initial non-small cell lung cancer (NSCLC). Methods: Retrospective chart review identified 161 patients (88 men and 73 women) with a median age of 70 years (range, 34-88 years) who underwent pulmonary resection for MSPLC between January 2000 and December 2009. Operative morbidity, mortality, and relevant factors were analyzed with χ2 test or Fisher exact test and Mann-Whitney U test. Survival was analyzed with Kaplan-Meier and Cox proportional hazard method. Results: The median interval between the initial and subsequent resection for MSPLC was 42.7 months (range, 7-205 months). There was no operative mortality and postoperative complication rate was 29%. In multivariate analysis, ipsilateral operation (P = .0002) and a lower predicted preoperative percent forced expiratory volume in the first second (P = .0035) were significant risk factors for postoperative complications. Five-year overall survival rates after resection of the initial and second metachronous NSCLC were 87.4% and 60.8%, respectively. Significant negative long-term prognostic factors for survival following resection of a MSPLC in multivariate analysis were tumor size >2 cm (P = .003) and number of pack years of smoking (P = .005). Metastatic nodal disease (P = .19) or a sublobar resection (P = .17) were not associated with worse survival. Conclusions: Surgical treatment of a MSPLC can be undertaken with 5-year survival rate of 60%. Expected operative morbidity and mortality are comparable to primary surgery. Tumors 2 cm or smaller are associated with improved survival and freedom from recurrence. Close long-term follow-up of patients who have undergone resection of NSCLC is recommended.",

author = "Masatsugu Hamaji and Allen, {Mark S.} and Cassivi, {Stephen D.} and Claude Deschamps and Nichols, {Francis C.} and Wigle, {Dennis A.} and Shen, {K. Robert}",

note = "Funding Information: Distinguishing MSPLC from recurrence or metastatic disease is important because the prognosis and treatment are dramatically different. We have shown previously that in patients who developed recurrent disease, survival was 51.8% at 2 years in patients with a MSPLC compared with 24.3% in those with local recurrence and only 8.9% in those with nonregional metastases. 4 Surgical resection remains the most effective treatment for patients with NSCLC, with 5-year survival rates approaching 70% at 5 years and 60% at 10 years. 7 Often patients who have MSPLC are considered to have more advanced disease and are not offered surgical resection, which negatively affects their survival. In this study, we report the largest series to date of surgically treated MSPLC. We have shown that patients with stages IA and IB MSPLC who were surgically treated had a 3-year survival of 73.4% and 66.7%, respectively. This compares favorably to patients with single lung cancers when matched for stage. 7 The 5- and 10-year survival rates of 60.8% and 20% we found in our study are somewhat higher than what other investigators have reported. In a report on 51 patients who underwent surgical treatment of second primary lung cancers, Aziz and colleagues 8 reported a 5-year survival for patients with metachronous second primary lung cancer of 44%. Similarly Adebonojo and colleagues 3 reported a 5-year survival of 37% in 37 patients who underwent resection of metachronous second primary lung cancers at the Walter Reed Army Medical Center. One possible explanation for this difference in results is that no uniform agreement exists as to what constitutes a second primary lung cancer and a variety of different criteria are used. The most commonly used criteria to define metachronous lung cancers were proposed by Martini and Melamed in 1975. 9 These criteria recommend that for lesions of similar histology, if there is no evidence of lymph node metastases in the common drainage basins and in the absence of extrathoracic metastases, it is reasonable to treat patients for second primary disease. These criteria have proven to be durable and have been used in a number of other surgical series of patients treated surgically for MSPLC. 10 In our study we used the same criteria to define MPLCs that we used in our previous reports on MPLCs, which are a modification of the criteria originally set forth by Martini and Melamed. Using these criteria, the overall incidence of MSPLC of 5.1% in our series is similar to what other surgical series have reported. 5,8 Although some would argue that distinguishing MSPLC from local recurrence or metastatic disease using any criteria is an impossible task, if extrathoracic metastases can be excluded and the patient can tolerate a second or third pulmonary resection, we believe surgery should be considered because resection may offer the best chance for potential cure. There was no operative mortality in our series and the surgical morbidity for this group of patients compares very favorably to several large contemporary multi-institutional reports of patients undergoing major pulmonary resection for NSCLC. Postoperative complications of any kind occurred in 29.2% of patients in this study, which is lower than the 38% complication rate reported in both groups of patients who participated in the randomized, prospective American College of Surgeons Oncology Group Z0030 trial of lymph node sampling versus mediastinal lymph node dissection for early stage lung cancer. 11 Similarly, using the definition of major morbidity set forth in a recent study of the Society of Thoracic Surgeons General Thoracic Database, the major morbidity rate for patients in this study was 5.6% compared with a major morbidity rate of 7.9% among the 18,800 patients who underwent lung cancer operations between January 1, 2002, and June 30, 2008, performed at 111 participating centers. 12 These results are somewhat surprising because one might intuitively expect to find a higher mortality and morbidity rate in this group of patients compared with patients undergoing primary lung cancer surgery. This is particularly the case given the reoperative nature of a second, and in some cases, third operation in patients who had already undergone substantial prior lung resection. Of the 161 patients in this study, 78.3% had undergone prior lobectomy and 4.3% had undergone pneumonectomy. In addition, 30% of patients underwent reoperative surgery on the ipsilateral side. Multivariate analysis did show that lower predicted FEV1 and reoperation in the ipsilateral side of the chest as the first operation were predictors of a higher risk of postoperative complications. Our results are difficult to compare with other published surgical series of MPLCs because none of the other large series have analyzed postoperative complications, focussing exclusively on operative mortality. The generalizability of our favorable results in this group of complex patients also needs to be tempered by an acknowledgment that the patients in our series were highly selected and results obtained in a highly specialized practice such as ours may not be broadly applicable to other practice settings. To identify factors associated with improved survival, univariate and multivariate analysis of a large number of clinical variables was performed. On multivariate analysis, only tumor size >2 cm and number of pack years of smoking were independent predictors of worse survival after resection of a MSPLC. These results are both novel findings. Our finding that the 2 cm cutpoint was such a strong independent predictor of survival is supported by the recent changes to the T-stage descriptor implemented by the International Association for the Study of Lung Cancer in the seventh edition of the TNM classification for lung cancer. 7,13 T1 tumors were subdivided into 2 prognostic groups: those ≤2 cm (T1a) and those larger than 2 cm but no larger than 3 cm (T1b). Our finding that smaller tumors have a favorable survival should highlight the need for close follow-up of patients with resected NSCLC with CT scanning. Although smoking status has not been analyzed as an independent predictor of survival in previous studies of MSPLC, 3,8,14 smoking status has been shown to be a significant independent prognostic factor predictive of inferior long-term survival in patients undergoing surgery for NSCLC. 15,16 There are a number of possible explanations for these observations. Smoking is associated with many factors that may contribute to worse cancer survival: lower socioeconomic status, poorer nutrition, comorbidity, impaired immune function, and exposure to oncogenic substances that result in an increased mutation burden that may lead to accelerated carcinogenesis and progression. Of these, comorbidity may be one of the most important factors because smoking is associated with numerous serious other diseases in addition to lung cancer. The US Surgeon General concluded that smoking accounts for 82% of chronic obstructive pulmonary disease-related deaths, 21% of coronary heart disease-related deaths, and 18% of deaths from stroke. 17 In their original 1975 publication describing the Memorial-Sloan Kettering experience with 32 patients with MSPLC, Martini and Melamed 9 proposed that for tumors of the same histology that a DFI of at least 2 years was required to be considered a metachronous lung cancer. Using these criteria, in their 1991 follow-up report on 78 patients with MSPLC, they found that survival was significantly better when the interval between 2 metachronous tumors was ≥24 months. 18 We modified the criteria proposed by Martini and Melamed to define metachronous tumors by eliminating the requirement of a DFI of at least 2 years to be able to validate if that criteria is associated with survival. We analyzed DFIs of 2, 3, and 5 years as well as if the DFI was <2 years or ≥2 years, and did not find any association with survival. This suggests to us that a DFI of at least 2 years should not be used as strict criteria to distinguish metachronous lung cancer from more advanced states of disease. Continued and careful long-term follow-up is necessary for all patients who have undergone resection of primary NSCLC and is the mainstay of diagnosis of MSPLC. Even after curative resection of a NSCLC, it is estimated that the risk of developing a second MSPLC is 1% to 2% per patient per year. 19-21 In some series 68% to 100% of patients with metachronous lung cancers were asymptomatic and had the new primary cancer detected by radiographic methods. 14,22,23 In our series all of the patients were asymptomatic and had the MSPLC detected by CXR or CT scan. Close follow-up with radiographic studies are particularly important during the first 3 years following resection of NSCLC because some series have found that a MSPLC develops in more than 50% of patients during this time. 14 Our data was consistent with this, as 44% of 161 patients developed a MSPLC within the first 3 years following resection of the primary NSCLC. We recommend lifelong close follow-up of patients who have undergone resection of NSCLC because a MSPLC developed in 33.6% of the patients our study more than 5 years following their first NSCLC operation and in 6.9% of patients more than 10 years later. This is consistent with what other investigators have found. Mathisen and colleagues 14 found that 25% of patients developed a second primary more than 5 years after the first primary cancer was resected, and Temeck and colleagues 24 found a 16% incidence of second lung primaries in patients who survived 10 years. Results from the National Cancer Institute sponsored randomized phase III National Lung Screening Trial for the first time has provided level-1 evidence that low-dose chest CT screening reduced lung cancer-specific mortality by 20% in a patient population believed to be at high risk for lung cancer. 25 Interestingly, in our study we found that survival following surgical treatment of a MSPLC was not associated with follow-up with CT scan or CXR. We suspect that this is due to the relatively small number of patients in our study. The National Lung Screening Trial randomized 53,454 patients, and was the first randomized trial to ever demonstrate efficacy of a low-dose chest CT screening program. Although 5 different medical societies (ie, American College of Chest Physicians, American College of Radiology, American Society of Clinical Oncology, European Society for Medical Oncology, and National Comprehensive Cancer Network) have put forward guidelines providing specific recommendations for surveillance methods in patients treated for NSCLC, 21 there is wide divergence among the guidelines regarding recommendations for chest imaging. Whereas European Society for Medical Oncology and American Society of Clinical Oncology guidelines do not recommend any chest imaging, the American College of Radiology recommends a CXR every 2 to 4 months and a CT scan every 12 months. The American College of Chest Physicians guidelines recommend a CXR or CT scan every 6 months, and the National Comprehensive Cancer Network guidelines recommend a CT scan every 6 months. Because the issues of radiographic detection of asymptomatic recurrent or metachronous cancer after treatment with curative intent are similar to those of early detection of primary cancer with screening programs in high-risk patients, we believe that the data from the National Lung Screening Trial can be extrapolated to justify close surveillance of patients treated for NSCLC with low-dose chest CT scan. However, we do not believe there is sufficient evidence at present to make any recommendations about specific practice guidelines regarding the frequency of the imaging studies. There are several important potential limitations of this study. This was a single institution experience, and as is the case with analysis of all single institution studies, the issue of external validity is relevant. Futhermore, due to the retrospective nature of the study, the results are based on a highly selected group of patients, and there is certainly a degree of selection bias in the study. We only analyzed patients who were surgically treated, and therefore are unable to compare the outcomes of this group with patients with MSPLC who were never offered or refused surgery and were treated medically. Finally, the incidence of MSPLC is still relatively low, and many of the subgroups we analyzed to identify covariates associated with survival had low numbers of patients. The low numbers within these subgroups may explain the lack of statistical difference in survival between patients with nodal metastases and those whose cancers were TNM stage N0, higher- versus lower-stage disease, and the extent of resection. ",

year = "2013",

month = mar,

doi = "10.1016/j.jtcvs.2012.12.051",

language = "English (US)",

volume = "145",

pages = "683--691",

journal = "Journal of Thoracic and Cardiovascular Surgery",

issn = "0022-5223",

publisher = "Mosby Inc.",

number = "3",

}

TY - JOUR

T1 - Surgical treatment of metachronous second primary lung cancer after complete resection of non-small cell lung cancer

AU - Hamaji, Masatsugu

AU - Allen, Mark S.

AU - Cassivi, Stephen D.

AU - Deschamps, Claude

AU - Nichols, Francis C.

AU - Wigle, Dennis A.

AU - Shen, K. Robert

N1 - Funding Information: Distinguishing MSPLC from recurrence or metastatic disease is important because the prognosis and treatment are dramatically different. We have shown previously that in patients who developed recurrent disease, survival was 51.8% at 2 years in patients with a MSPLC compared with 24.3% in those with local recurrence and only 8.9% in those with nonregional metastases. 4 Surgical resection remains the most effective treatment for patients with NSCLC, with 5-year survival rates approaching 70% at 5 years and 60% at 10 years. 7 Often patients who have MSPLC are considered to have more advanced disease and are not offered surgical resection, which negatively affects their survival. In this study, we report the largest series to date of surgically treated MSPLC. We have shown that patients with stages IA and IB MSPLC who were surgically treated had a 3-year survival of 73.4% and 66.7%, respectively. This compares favorably to patients with single lung cancers when matched for stage. 7 The 5- and 10-year survival rates of 60.8% and 20% we found in our study are somewhat higher than what other investigators have reported. In a report on 51 patients who underwent surgical treatment of second primary lung cancers, Aziz and colleagues 8 reported a 5-year survival for patients with metachronous second primary lung cancer of 44%. Similarly Adebonojo and colleagues 3 reported a 5-year survival of 37% in 37 patients who underwent resection of metachronous second primary lung cancers at the Walter Reed Army Medical Center. One possible explanation for this difference in results is that no uniform agreement exists as to what constitutes a second primary lung cancer and a variety of different criteria are used. The most commonly used criteria to define metachronous lung cancers were proposed by Martini and Melamed in 1975. 9 These criteria recommend that for lesions of similar histology, if there is no evidence of lymph node metastases in the common drainage basins and in the absence of extrathoracic metastases, it is reasonable to treat patients for second primary disease. These criteria have proven to be durable and have been used in a number of other surgical series of patients treated surgically for MSPLC. 10 In our study we used the same criteria to define MPLCs that we used in our previous reports on MPLCs, which are a modification of the criteria originally set forth by Martini and Melamed. Using these criteria, the overall incidence of MSPLC of 5.1% in our series is similar to what other surgical series have reported. 5,8 Although some would argue that distinguishing MSPLC from local recurrence or metastatic disease using any criteria is an impossible task, if extrathoracic metastases can be excluded and the patient can tolerate a second or third pulmonary resection, we believe surgery should be considered because resection may offer the best chance for potential cure. There was no operative mortality in our series and the surgical morbidity for this group of patients compares very favorably to several large contemporary multi-institutional reports of patients undergoing major pulmonary resection for NSCLC. Postoperative complications of any kind occurred in 29.2% of patients in this study, which is lower than the 38% complication rate reported in both groups of patients who participated in the randomized, prospective American College of Surgeons Oncology Group Z0030 trial of lymph node sampling versus mediastinal lymph node dissection for early stage lung cancer. 11 Similarly, using the definition of major morbidity set forth in a recent study of the Society of Thoracic Surgeons General Thoracic Database, the major morbidity rate for patients in this study was 5.6% compared with a major morbidity rate of 7.9% among the 18,800 patients who underwent lung cancer operations between January 1, 2002, and June 30, 2008, performed at 111 participating centers. 12 These results are somewhat surprising because one might intuitively expect to find a higher mortality and morbidity rate in this group of patients compared with patients undergoing primary lung cancer surgery. This is particularly the case given the reoperative nature of a second, and in some cases, third operation in patients who had already undergone substantial prior lung resection. Of the 161 patients in this study, 78.3% had undergone prior lobectomy and 4.3% had undergone pneumonectomy. In addition, 30% of patients underwent reoperative surgery on the ipsilateral side. Multivariate analysis did show that lower predicted FEV1 and reoperation in the ipsilateral side of the chest as the first operation were predictors of a higher risk of postoperative complications. Our results are difficult to compare with other published surgical series of MPLCs because none of the other large series have analyzed postoperative complications, focussing exclusively on operative mortality. The generalizability of our favorable results in this group of complex patients also needs to be tempered by an acknowledgment that the patients in our series were highly selected and results obtained in a highly specialized practice such as ours may not be broadly applicable to other practice settings. To identify factors associated with improved survival, univariate and multivariate analysis of a large number of clinical variables was performed. On multivariate analysis, only tumor size >2 cm and number of pack years of smoking were independent predictors of worse survival after resection of a MSPLC. These results are both novel findings. Our finding that the 2 cm cutpoint was such a strong independent predictor of survival is supported by the recent changes to the T-stage descriptor implemented by the International Association for the Study of Lung Cancer in the seventh edition of the TNM classification for lung cancer. 7,13 T1 tumors were subdivided into 2 prognostic groups: those ≤2 cm (T1a) and those larger than 2 cm but no larger than 3 cm (T1b). Our finding that smaller tumors have a favorable survival should highlight the need for close follow-up of patients with resected NSCLC with CT scanning. Although smoking status has not been analyzed as an independent predictor of survival in previous studies of MSPLC, 3,8,14 smoking status has been shown to be a significant independent prognostic factor predictive of inferior long-term survival in patients undergoing surgery for NSCLC. 15,16 There are a number of possible explanations for these observations. Smoking is associated with many factors that may contribute to worse cancer survival: lower socioeconomic status, poorer nutrition, comorbidity, impaired immune function, and exposure to oncogenic substances that result in an increased mutation burden that may lead to accelerated carcinogenesis and progression. Of these, comorbidity may be one of the most important factors because smoking is associated with numerous serious other diseases in addition to lung cancer. The US Surgeon General concluded that smoking accounts for 82% of chronic obstructive pulmonary disease-related deaths, 21% of coronary heart disease-related deaths, and 18% of deaths from stroke. 17 In their original 1975 publication describing the Memorial-Sloan Kettering experience with 32 patients with MSPLC, Martini and Melamed 9 proposed that for tumors of the same histology that a DFI of at least 2 years was required to be considered a metachronous lung cancer. Using these criteria, in their 1991 follow-up report on 78 patients with MSPLC, they found that survival was significantly better when the interval between 2 metachronous tumors was ≥24 months. 18 We modified the criteria proposed by Martini and Melamed to define metachronous tumors by eliminating the requirement of a DFI of at least 2 years to be able to validate if that criteria is associated with survival. We analyzed DFIs of 2, 3, and 5 years as well as if the DFI was <2 years or ≥2 years, and did not find any association with survival. This suggests to us that a DFI of at least 2 years should not be used as strict criteria to distinguish metachronous lung cancer from more advanced states of disease. Continued and careful long-term follow-up is necessary for all patients who have undergone resection of primary NSCLC and is the mainstay of diagnosis of MSPLC. Even after curative resection of a NSCLC, it is estimated that the risk of developing a second MSPLC is 1% to 2% per patient per year. 19-21 In some series 68% to 100% of patients with metachronous lung cancers were asymptomatic and had the new primary cancer detected by radiographic methods. 14,22,23 In our series all of the patients were asymptomatic and had the MSPLC detected by CXR or CT scan. Close follow-up with radiographic studies are particularly important during the first 3 years following resection of NSCLC because some series have found that a MSPLC develops in more than 50% of patients during this time. 14 Our data was consistent with this, as 44% of 161 patients developed a MSPLC within the first 3 years following resection of the primary NSCLC. We recommend lifelong close follow-up of patients who have undergone resection of NSCLC because a MSPLC developed in 33.6% of the patients our study more than 5 years following their first NSCLC operation and in 6.9% of patients more than 10 years later. This is consistent with what other investigators have found. Mathisen and colleagues 14 found that 25% of patients developed a second primary more than 5 years after the first primary cancer was resected, and Temeck and colleagues 24 found a 16% incidence of second lung primaries in patients who survived 10 years. Results from the National Cancer Institute sponsored randomized phase III National Lung Screening Trial for the first time has provided level-1 evidence that low-dose chest CT screening reduced lung cancer-specific mortality by 20% in a patient population believed to be at high risk for lung cancer. 25 Interestingly, in our study we found that survival following surgical treatment of a MSPLC was not associated with follow-up with CT scan or CXR. We suspect that this is due to the relatively small number of patients in our study. The National Lung Screening Trial randomized 53,454 patients, and was the first randomized trial to ever demonstrate efficacy of a low-dose chest CT screening program. Although 5 different medical societies (ie, American College of Chest Physicians, American College of Radiology, American Society of Clinical Oncology, European Society for Medical Oncology, and National Comprehensive Cancer Network) have put forward guidelines providing specific recommendations for surveillance methods in patients treated for NSCLC, 21 there is wide divergence among the guidelines regarding recommendations for chest imaging. Whereas European Society for Medical Oncology and American Society of Clinical Oncology guidelines do not recommend any chest imaging, the American College of Radiology recommends a CXR every 2 to 4 months and a CT scan every 12 months. The American College of Chest Physicians guidelines recommend a CXR or CT scan every 6 months, and the National Comprehensive Cancer Network guidelines recommend a CT scan every 6 months. Because the issues of radiographic detection of asymptomatic recurrent or metachronous cancer after treatment with curative intent are similar to those of early detection of primary cancer with screening programs in high-risk patients, we believe that the data from the National Lung Screening Trial can be extrapolated to justify close surveillance of patients treated for NSCLC with low-dose chest CT scan. However, we do not believe there is sufficient evidence at present to make any recommendations about specific practice guidelines regarding the frequency of the imaging studies. There are several important potential limitations of this study. This was a single institution experience, and as is the case with analysis of all single institution studies, the issue of external validity is relevant. Futhermore, due to the retrospective nature of the study, the results are based on a highly selected group of patients, and there is certainly a degree of selection bias in the study. We only analyzed patients who were surgically treated, and therefore are unable to compare the outcomes of this group with patients with MSPLC who were never offered or refused surgery and were treated medically. Finally, the incidence of MSPLC is still relatively low, and many of the subgroups we analyzed to identify covariates associated with survival had low numbers of patients. The low numbers within these subgroups may explain the lack of statistical difference in survival between patients with nodal metastases and those whose cancers were TNM stage N0, higher- versus lower-stage disease, and the extent of resection.

PY - 2013/3

Y1 - 2013/3

N2 - Objective: To clarify the perioperative and oncologic outcome of pulmonary resection for a metachronous second primary lung cancer (MSPLC) following resection of an initial non-small cell lung cancer (NSCLC). Methods: Retrospective chart review identified 161 patients (88 men and 73 women) with a median age of 70 years (range, 34-88 years) who underwent pulmonary resection for MSPLC between January 2000 and December 2009. Operative morbidity, mortality, and relevant factors were analyzed with χ2 test or Fisher exact test and Mann-Whitney U test. Survival was analyzed with Kaplan-Meier and Cox proportional hazard method. Results: The median interval between the initial and subsequent resection for MSPLC was 42.7 months (range, 7-205 months). There was no operative mortality and postoperative complication rate was 29%. In multivariate analysis, ipsilateral operation (P = .0002) and a lower predicted preoperative percent forced expiratory volume in the first second (P = .0035) were significant risk factors for postoperative complications. Five-year overall survival rates after resection of the initial and second metachronous NSCLC were 87.4% and 60.8%, respectively. Significant negative long-term prognostic factors for survival following resection of a MSPLC in multivariate analysis were tumor size >2 cm (P = .003) and number of pack years of smoking (P = .005). Metastatic nodal disease (P = .19) or a sublobar resection (P = .17) were not associated with worse survival. Conclusions: Surgical treatment of a MSPLC can be undertaken with 5-year survival rate of 60%. Expected operative morbidity and mortality are comparable to primary surgery. Tumors 2 cm or smaller are associated with improved survival and freedom from recurrence. Close long-term follow-up of patients who have undergone resection of NSCLC is recommended.

AB - Objective: To clarify the perioperative and oncologic outcome of pulmonary resection for a metachronous second primary lung cancer (MSPLC) following resection of an initial non-small cell lung cancer (NSCLC). Methods: Retrospective chart review identified 161 patients (88 men and 73 women) with a median age of 70 years (range, 34-88 years) who underwent pulmonary resection for MSPLC between January 2000 and December 2009. Operative morbidity, mortality, and relevant factors were analyzed with χ2 test or Fisher exact test and Mann-Whitney U test. Survival was analyzed with Kaplan-Meier and Cox proportional hazard method. Results: The median interval between the initial and subsequent resection for MSPLC was 42.7 months (range, 7-205 months). There was no operative mortality and postoperative complication rate was 29%. In multivariate analysis, ipsilateral operation (P = .0002) and a lower predicted preoperative percent forced expiratory volume in the first second (P = .0035) were significant risk factors for postoperative complications. Five-year overall survival rates after resection of the initial and second metachronous NSCLC were 87.4% and 60.8%, respectively. Significant negative long-term prognostic factors for survival following resection of a MSPLC in multivariate analysis were tumor size >2 cm (P = .003) and number of pack years of smoking (P = .005). Metastatic nodal disease (P = .19) or a sublobar resection (P = .17) were not associated with worse survival. Conclusions: Surgical treatment of a MSPLC can be undertaken with 5-year survival rate of 60%. Expected operative morbidity and mortality are comparable to primary surgery. Tumors 2 cm or smaller are associated with improved survival and freedom from recurrence. Close long-term follow-up of patients who have undergone resection of NSCLC is recommended.

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UR - http://www.scopus.com/inward/citedby.url?scp=84873918352&partnerID=8YFLogxK

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ER -

Surgical treatment of metachronous second primary lung cancer after complete resection of non-small cell lung cancer

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