Lung Cancer Invading the Chest Wall: A Plea for En-Bloc Resection but the Need for New Treatment Strategies

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1 Lung Cancer Invading the Chest Wall: A Plea for En-Bloc Resection but the Need for New Treatment Strategies Christophe Doddoli, MD, Benoit D Journo, MD, Françoise Le Pimpec-Barthes, MD, Antoine Dujon, MD, Christophe Foucault, MD, Pascal Thomas, MD, and Marc Riquet, MD, PhD Department of Thoracic Surgery, Hôpital Sainte-Marguerite, Marseille, Department of Thoracic Surgery, Hôpital Européen Georges Pompidou, Paris, Thoracic Surgery Unit, Centre Médico-Chirurgicale du Cèdre, Boisguillaume, and Unité Propre de Recherche et d Enseignement Supérieur, Equipe d Acceuil 2201, Institut Fédératif de Recherche, Jean Roche, Marseille, France Background. Factors influencing survival of patients with a nonsmall-cell lung cancer (NSCLC) invading the parietal pleura or the chest wall are still controversial. The aim of this study was to assess prognostic factors in completely resected pt3 chest wall NSCLC patients. Methods. We retrospectively reviewed a three-center experience between 1984 and 2002 with 309 patients. Results. There were 269 male and 40 female patients. Pulmonary resections consisted of 13 wedge resections or segmentectomies, 211 lobectomies, 6 bilobectomies, and 79 pneumonectomies. One hundred patients underwent extrapleural mobilization, and 209, en-bloc resection. Tumors were staged as stages IIB (n 212) and IIIA (n 97). Overall 5-year survival rates were 40% and 12% for stage IIB and IIIA, respectively (p < 10 4 ). Multivariate analysis shows male sex and bigger tumor size as independent indicators of poor prognosis in stage IIB patients. In stage IIB patients with a chest wall invasion limited to the parietal pleura, en-bloc resections provided higher 5-year survival rates when compared with extrapleural resections (60.3% versus 39.1%; p 0.03). In stage IIIA patients, multivariate analysis disclosed two independent prognostic factors: the number of resected ribs and adjuvant parietal and mediastinal radiotherapy. Conclusions. The presence of lymph node metastases has a disastrous impact on survival in this subset of patients. En-bloc resection is strongly suggested to be the standard of surgical care, and adjuvant radiotherapy does not seem to be necessary in N0 patients when a complete R0 resection has been achieved. For huge tumors (larger than 6 cm), this report suggests that the role of perioperative chemotherapy needs further evaluation. (Ann Thorac Surg 2005;80: ) 2005 by The Society of Thoracic Surgeons Accepted for publication March 21, Address correspondence to Dr Doddoli, Sainte-Marguerite Hospital, 270, Blvd de Sainte-Marguerite, Marseille Cedex 09, France; christophe.doddoli@mail.ap-hm.fr. The treatment of patients with a nonsmall-cell lung cancer (NSCLC) invading the chest wall remains under debate because of questions about the unresolved issue of the treatment strategy for a locally advanced disease with or without multimodality approaches, and the technical challenge of an extended operation that offers a complete resection. Despite a substantial literature, factors affecting survival are still unclear, excepted the incompleteness of the resection and the presence of lymph node metastases [1 4]. One of the most frequent bias encountered in the available literature is the wide variety of medical and surgical treatment options in most series. To limit as much as possible the influence of such confounding variables, we focused our analysis on a selected sample of 309 patients free of any treatment before surgery, and who received a pathologically proven complete R0 resection. The aim of this study was to identify potential patient-related, tumor-related, and treatment-related factors that may impact on the longterm outcome of patients presenting with a NSCLC invading the chest wall. Patients and Methods Patients From 1984 to 2002, 309 consecutive patients with a pt3 NSCLC invading the chest wall were surgically treated with a complete (R0) resection at three institutions (Sainte-Marguerite Hospital, European Georges Pompidou Hospital, and Boisguillaume Surgical Center). All these patients underwent surgery as the first treatment. Patients with a tumor classified postoperatively as T3 due to the invasion of the diaphragm, the mediastinal pleura, or the pericardium were not included. The subset of patients with a superior sulcus tumor included in the present study had no Pancoast syndrome at presentation, and all received a complete R0 resection through a posterior approach. Not included were those patients with a Pancoast syndrome, or who were deemed to be of doubtful resectability after imaging investigations. All of them received induction chemoradiotherapy, and some 2005 by The Society of Thoracic Surgeons /05/$30.00 Published by Elsevier Inc doi: /j.athoracsur

2 Ann Thorac Surg DODDOLI ET AL 2005;80: LUNG CANCER INVOLVING THE CHEST WALL of them were operated on through an anterior or a combined anterior and posterior approach. Patient charts were identified by screening of a database into which data were entered prospectively for any patient undergoing surgery for lung malignancy at our departments. When chest wall invasion was proven preoperatively (invasion beyond parietal pleura clearly evident on computed tomography (CT) scan or positive bone scintigraphy on ribs), or suspected clinically (chest pain), an en-bloc resection was scheduled. En-bloc resection was also performed in case of intraoperative evidence of deep parietal invasion. Otherwise extrapleural dissection (parietal pleurectomy) was performed when the parietal pleura could be freed easily from the chest wall. One hundred patients (32.4%) underwent an extrapleural resection and the analysis of the specimen confirmed that the depth of chest wall invasion was confined to the parietal pleura in all of them. Two hundred and nine patients (67.6%) had an en-bloc chest wall resection. Lymphadenectomy was done uniformly betweens centers, and this was precisely the reason why the authors chose to pool their experience. An ipsilateral hilar, scissural, and mediastinal lymph node dissection was performed routinely in all patients, and this was checked on the pathology report. Operative reports, pathology reports, hospital reports, and outclinic charts were reviewed. Demographic data of patients and first symptom were collected. Preoperative workup included routine chest radiography, and thoracic and abdominal CT scan. Bone scanning and brain CT scan were performed selectively on the basis of clinical clues. Preoperative workup also included routine biochemical profile, bronchoscopy, pulmonary function tests, and arterial blood gas analysis at rest, as well as quantitative ventilation and perfusion scans in patients in whom predicted postoperative forced expiratory volume in 1 second (FEV 1 ) could be estimated lower than 1 L. Mediastinoscopy was not routinely performed as part of the preoperative workup, except to rule out a N2 disease when suspected on the basis of enlarged mediastinal lymph nodes at CT scan. Types of pulmonary and parietal resections and postoperative complications were collected as well. Postoperative pathological analysis included pathologic type, tumor size, ptnm assessment, chest wall in-depth invasion, presence of vessel invasion, and number of resected ribs. Adjuvant therapy (radiotherapy, chemotherapy, or combination of both) was noted, but only postoperative radiotherapy was submitted to analysis given the wide variety of drug regimens. There was also no uniform attitude to select patients for adjuvant radiotherapy after complete resection. When performed, it consisted of parietal radiotherapy in case of stage IIB disease, and parietal and mediastinal radiotherapy in case of stage IIIA disease. Statistical Analysis Survival was studied in stage IIB (T3N0M0) and IIIA (T3N1M0 and T3N2M0) patients. The following variables were considered as potential prognostic factors of survival: age ( 60 years versus 60 years), sex, side of the resection, number of resected ribs ( 2 versus 2), type of operation (extrapleural versus en-bloc resection), pathologic type (squamous cell carcinoma versus adenocarcinoma versus others), tumor size ( 6 cm versus 6 cm), depth of invasion of the chest wall (pleura versus pleura plus soft tissues versus pleura plus soft tissue plus ribs), blood vessels invasion (yes versus no), and adjuvant radiotherapy (yes versus no). Survival was calculated from the date of surgery until death or the date of last follow-up. Actuarial survival curves were calculated using the Kaplan-Meier method. Comparisons were made using the log-rank test. Univariate and multivariate analysis were performed using Cox proportional hazards regression model to determine factors potentially predicting survival. The Cox model was used to incorporate in the same model any explanatory variables with a p value less than Forward stepwise procedure and likelihood ratio tests were used to select the variables with the greatest prognostic value (p 0.05). This statistical analysis was performed by using the SPSS V10.0 software package (SPSS, Chicago, Illinois). Results 2033 The demographic and surgical data and the pathologic features are shown in Table 1. Thirteen patients had a limited resection because of a poor pulmonary functional status. Complications occurred in 101 patients (32.7%) and resulted in 24 postoperative deaths (7.8%). Respiratory failure was the leading cause of death (n 17). Postoperative mortality rates were 5.7% (12 of 211), 33.3% (2 of 6), and 12.7% (10 of 79) for lobectomy, bilobectomy, and pneumonectomy, respectively. In the 209 patients having undergone an en-bloc resection (n 209), the tumor invaded the parietal pleura only in 38 patients, the pleura and soft tissues in 75, and the pleura, soft tissues and ribs in 96. Large chest wall defects were repaired using a prosthesis in 84 patients (40%): flexible mesh (Vicryl; Ethicon, Somerville, New Jersey) in 68 cases; Marlex (CR Bard, Murray Hill, New Jersey) in 14 cases, and Gore-Tex (Gore and Associates, Flagstaff, Arizona) in 2 cases. Muscle transpositions were associated in 3 cases. The distribution of node involvement according to the depth of chest wall invasion is shown in Table 2. Adjuvant radiotherapy, chemotherapy, or associated radiochemotherapy were administered to, respectively, 131, 10, and 36 patients. At completion of the study, follow-up was complete for 82.8% of patients. The status of the patients at last follow-up is given by Table 3. Median survival was 19 months, and the overall 5-year survival rate was 30.7%. Five-year survival according to the N status was 40%, 23.8%, and 8.4% in cases of N0, N1, and N2 disease, respectively. The difference of survival between N1 and N2 patients was close to statistical significance (p 0.056). Five-year survival rates were 40% and 12% for stage IIB and IIIA, respectively (p 10 4 ; Fig 1). Survival with reference to various variables in stage IIB patients is shown in Table 4. A poorer survival was shown in case of tumor size bigger than 6 cm (Fig 2). GENERAL THORACIC

3 2034 DODDOLI ET AL Ann Thorac Surg LUNG CANCER INVOLVING THE CHEST WALL 2005;80: Table 1. Demographic and Surgical Data and Pathologic Features of the 309 Patients Sex Male 269 (87%) Female 40 (13%) Age (years) Mean Range Location Right 175 (57%) Left 134 (43%) Symptoms Pain 159 (51.46%) Hemoptysis 19 (6.15%) Pain and hemoptysis 11 (3.56%) Others 70 (22.65%) No symptom 50 (16.18%) Parenchymal resection Lobectomy 211 (68.28%) Right upper 110 Right lower 12 Middle 2 Left upper 76 Left lower 11 Bilobectomy 6 (1.95%) Pneumonectomy 79 (25.57%) Wedge/segmentectomy 13 (4.2%) Tumor size (cm) Mean Range Chest wall resection rib 27 (12.92%) 2 ribs 66 (31.57%) 3 ribs 80 (38.28%) 4 ribs 33 (15.8%) 5 ribs 3 (1.43%) Histology Squamous cell carcinoma 130 (42.07%) Adenocarcinoma 100 (35.6%) Others 69 (22.33%) Five-year survival was also negatively influenced by male sex and chest wall resection including more than 2 ribs. Survival was not significantly modified by the type of pulmonary and chest wall resection, the depth of chest wall invasion, histology, and performance of adjuvant parietal radiotherapy. At multivariate analysis, two independent prognostic factors entered the model: sex and tumor size (Table 5). For these tumors IIB, an en-bloc resection was found to increase survival significantly in patients with invasion limited to the parietal pleura (39.1% for extrapleural mobilization versus 60.3% for en-bloc resection, p 0.03; Fig 3). The status at last follow-up of these patients is shown in Table 6. The survival of stage IIIA patients with reference to various variables is shown in Table 7. At multivariate analysis, two independent prognostic factors entered the model: number of resected ribs, and adjuvant parietal and mediastinal radiotherapy (Table 8). In these stage IIIA patients, overall 5-year survival was not influenced by the type of the parietal resection when the tumoral invasion was limited to the parietal pleura (13.9% for extrapleural mobilization versus 0 % for en-bloc resection, p 0.19). Comment The present results show several particular features of chest wall pt3 (stage IIB and IIIA), with the limitations due to the retrospective and multicenter nature of this study, the design of which was dictated by the relatively rare frequency of such disease in the setting of a surgical treatment: fewer than 5% of all pulmonary resections for lung cancer performed during the same period at our institutions and 5.6% in others [5]. Our choice to include patients with a superior sulcus tumor may be questionable given their usual worse prognostic profile and different treatment strategies, including induction chemoradiotherapy. We emphasize on the facts that only those patients without a Pancoast syndrome at presentation, and having received a complete R0 resection after a first-line surgery through a posterior approach were considered. These criteria undoubtedly define a highly selected subset of patients for whom there is no clear rationale to anticipate a different outcome than that of patients operated on from a tumor invading other areas of the chest wall. Of note, these patients are not usually excluded from those studies dealing with combined modalities treatment, although one may oppose that their outcome would probably bias the overall results favorably. Demographic and clinical features in our study were not different of what is typically reported in the literature [4 8]. Pulmonary resections consisting of a majority of lobectomy are also usual [3 11]. We performed a relatively high percentage of pneumonectomy (25%), did Table 2. Distribution of Node Involvement in the Chest Wall pt3 N0 (%) N1 (%) N2 (%) Total Pleura 91 (65.94) 16 (11.59) 31 (22.46) 138 Pleura soft tissues 53 (70.67) 8 (10.67) 14 (18.67) 75 Pleura soft tissue ribs 68 (70.83) 8 (8.33) 20 (20.83) 96 Total

4 Ann Thorac Surg DODDOLI ET AL 2005;80: LUNG CANCER INVOLVING THE CHEST WALL Table 3. Patient s Status at Last Follow-Up Status Extrapleural Resection n 100 En-Bolc Resection n 209 All Patients n 309 p Value Dies postoperatively test No recurrence test Alive Dead With recurrence test Alive Dead GENERAL THORACIC Downey and associates [4] and Magdeleinat and coworkers [6], who reported similar percentages of 20% and 27%, respectively. After large parietal resections, 40% of our patients required a dedicated reconstruction, mainly to avoid the incarceration of the scapula inside the chest wall defect after posterior resections, and to limit paradoxical chest wall motion for anterolateral defects. The percentage of such reconstruction varies from 0% to 64% in the literature [5 8, 11]. Postoperative mortality was in the range of what is reported by the literature [4, 6, 8, 11], but the rate observed after pneumonectomy was high (12.7%). Unfortunately, very few data are available regarding this topic, which makes comparison difficult [1, 8, 11]. Most papers reported on overall mortality, without emphasis or special attention to that of patients having received pneumonectomy [2, 4, 6, 9, 12, 13]. Most of the pathologic characteristics in this study do not differ from those reported in other major series. Mean tumor size ranged from 5.1 and 7.1 cm in the literature [1, 4, 9, 11, 14], and was 6.1 cm in the present series. Although a complete lymph node dissection was not performed routinely by all surgeons having published on this topic, the prevalence of N0 disease seems to be a relatively common feature, observed in about 60% of the reported cases [1, 3 7, 9, 11, 14], and in 68.6% in our experience. Survival and prognostic factors focused our attention because of the nonhomogeneous information brought by the literature. Five-year survival rate was 40% for our Fig 1. Overall survival according to the stage. stage IIB patients, whereas the usually reported rates range from 22% to 78.5% [1 9, 11]. This relatively large scale reflects patients samples of uneven sizes [1 3, 9], variable treatment modalities [1, 4 6, 9, 11], and different surgical policies [1 11]. Conversely, all authors join to underline the disastrous impact of the presence of lymph nodes metastases, with an attached 5-year survival around 10% (12% in our experience) [1, 8, 9, 12, 15], with some series culminating at 20% [2, 5, 6, 11] as the result of a stage migration effect (Will Rogers phenomenon) according to the proportion of patients with a clinically occult N disease [6, 11]. The results of our multivariate analysis clearly showed that the lymph node status canceled the impact of any other potential prognosticator. Obviously, this evidence should lead to improve selection methods to allocate those patients to multimodality strategies including induction therapies. Of note, our multivariate analysis identified the performance of adjuvant radiotherapy as an independent determinant of survival in stage IIIA patients, whereas it was not the case in stage IIB patients. This difference may be because, in most cases, radiotherapy consisted of parietal and mediastinal radiation in stage IIIA patients, but parietal radiation only in stage IIB patients. The second explanation relies on the adjunction of chemotherapy preferentially in stage IIIA patients. Anyway, one should point out that the chances for cure for T3 stage IIIA patients are so low that it remains unclear whether surgery is of any benefit for these patients, especially when a pneumonectomy is required. Tumor size is a classical factor in the study on survival in NSCLC. A 3-cm cutoff point separates T1 from T2 tumors, whereas a size larger than 3 cm is not ascribed any prognostic value. The cancer-related death risk does not seem to increase in line with tumor size for each of the pathologic stages, in a significant and independent fashion. For instance, stratifying patients with stage IA NSCLC according to their tumor size gave no apparent difference in survival [16, 17]. Conversely, tumors with a diameter of 5 cm or larger determine the same survival as some categories of T3N0M0 [18, 19]. Comparatively, stratifying our patients with pt3 chest wall NSCLC according to tumor size gave an apparent difference in survival for patients with a stage IIB tumor. We report a quite good 5-year survival rate (45.9%) for patients with a tumor size of less than 6 cm. Tumor size, by itself, thus

5 2036 DODDOLI ET AL Ann Thorac Surg LUNG CANCER INVOLVING THE CHEST WALL 2005;80: Table 4. Relationship Between Variables and 5-Year Survival for Patients Having Pathology Stage IIB Variable No. of Observations (n 212) 5 Years 95% Confidence Interval Lower Upper p Value Age 60 years years Sex Male Female Side of resection Right Left Resected ribs Histology Squamous cell carcinoma Adenocarcinoma Others Tumor size 6 cm cm In-depth chest wall invasion Pleura Pleura soft tissues Pleura soft tissue ribs Vessel invasion No Yes Adjuvant radiotherapy No Yes appears as a putatively strong prognostic factor of longterm outcome in pt3n0 chest wall patients. To our knowledge, this finding was not yet recognized for this pathologic stage. The explanation may be pragmatic only, as it may be more difficult to obtain wide and clear Fig 2. Overall survival according to the tumor size in stage IIB patients. surgical margins with huge tumors. As the primary goal of surgery remains a complete resection with free margins, as stressed by the absence of 2.5-year survivors among incompletely resected patients [2], this finding may be the rationale for investigating the value of induction therapy for huge tumors. Similar to the findings of Chapelier and associates [8], we found that the extent of the chest wall resection assessed by the number of removed ribs was a predictor of survival only at univariate analysis in stage IIB patients. In contrast, this variable entered the multivariate analysis of stage IIIA patients. Depth invasion of the chest wall was not correlated with survival, despite a poor prognosis in patients with N0 disease and invasion of all components of the chest wall. This finding was in agreement with some experiences [7, 11, 20], but in contrast with others in which survival was better when tumoral invasion was confined to the parietal pleura [4 6, 8, 21]. Among the patients with invasion limited to the parietal pleura, the type of resection (extrapleural mobilization or en-bloc resection) affected survival in cases of N0 disease. This result is consistent with previ-

6 Ann Thorac Surg DODDOLI ET AL 2005;80: LUNG CANCER INVOLVING THE CHEST WALL Table 5. Univariate and Multivariate Analyses of Prognostic Factors in Pathology Stage IIB Chest Wall Patients Variable p Value Univariate Analysis Hazard Ratio Multivariate Analysis % Confidence Interval 95% Confidence Interval Lower Upper p Value Hazard Ratio Lower Upper GENERAL THORACIC Age ( 60 vs years) Sex (female vs male) Side of resection (right vs left) Resected ribs ( vs 2) Histology Others vs ADK Others vs SCC Tumor size ( 6vs cm) In-depth chest wall invasion PvsP St PvsP ST R Vessels invasion (yes vs/no) Adjuvant radiotherapy (yes vs no) Type of resection (extrapleural vs en bloc) ADK adenocarcinoma; P pleura; P ST pleura soft tissues; P St R pleura soft tissue ribs; SCC squamous cell carcinoma. Fig 3. Overall survival according to the type of resection for tumors involving only parietal pleura in stage IIB patients. ously reported findings [3, 9]. The explanation of the benefit of this apparent overtreatment is probably artefactual. Indeed, performing a full-thickness en-bloc resection logically decreases the risk of leaving a residual disease. As a matter of fact, the analysis of the subgroup of N0 patients with a chest wall invasion limited to the parietal pleura suggested that patients undergoing extrapleural mobilization developed more local relapses (18%) than those treated by full-thickness en-bloc resection (4%), and in turn had a significantly worse survival rate as well. The absence of survival difference according to the type of chest wall resection noticed in N patients is probably due to the higher prognostic weight provided by a lymph node invasion, canceling that of a microscopically incomplete resection. So the concept of performing routinely an en-bloc resection even if the parietal pleura could easily be cleaved from the chest wall is strongly sustained by our results and is clinically relevant, even if this issue remains controversial [2, 4, 6, 13]. In our study, female sex was a significant predictor of long-term survival in stage IIB patients. Burkhart and associates [11] have recently reported a similar finding. However, this effect is usually pronounced at early disease stages [22 24]. Lung cancer in women when compared with men has generally the following characteristics: younger age of onset, less smoking, and more adenocarcinoma. Of note, these characteristics were not observed in our experience. Some reports suggest that NSCLC may be under hormonal control [25]. In addition, the presence of an allele loss that occurs more frequently in men and is associated with decreased survival has recently been reported [26].

7 2038 DODDOLI ET AL Ann Thorac Surg LUNG CANCER INVOLVING THE CHEST WALL 2005;80: Table 6. Status of IIB Patients With Involvement of Only Parietal Pleura Status at Last Follow-up Extrapleural Resection n 66 En-Bloc Resection n 25 p Value Died postoperatively (Fisher s test) No recurrence ( 2 test) Alive Dead 7 3 With local general recurrence (Fisher s test) Alive 2 0 Dead 10 1 With general recurrence only ( 2 test) Alive 4 1 Dead 21 6 Whether adjuvant radiotherapy is needed in chest wall pt3 NSCLC is still an open issue. We did not observe any difference in terms of local relapse and overall survival in stage IIB patients with regard to the administration of postoperative radiotherapy. In contrast, adjuvant radiotherapy increased survival in stage IIIA patients. It may be hypothesized that N0 patients having undergone a R0 resection did not need any adjuvant radiotherapy to achieve a suitable local control of the disease. Conversely, besides the bias due to the frequent adjunction of chemotherapy in stage IIIA patients, it may be speculated that mediastinal radiotherapy improved the local Table 7. Relationship Between Variables and 5-Year Survival for Patients Having Pathology State IIIA Variable No. of Observations (n 97) 5 Years 95% Confidence Interval Lower Upper p Value Age 60 years years Sex male Female Side of resection Right left Resected ribs Pathology Squamous cell carcinoma Adenocarcinoma Others Tumor size 6 cm cm In-depth chest wall invasion Pleura Pleura soft tissues Pleura soft tissue ribs Vessel invasion No Yes 19 0 Adjuvant radiotherapy No Yes

8 Ann Thorac Surg DODDOLI ET AL 2005;80: LUNG CANCER INVOLVING THE CHEST WALL Table 8. Univariate and Multivariate Analyses of Prognostic Factors in Pathology Stage IIIA Chest Wall Patients Variable p Value Univariate Analysis Hazard Ratio Multivariate Analysis % Confidence Interval 95% Confidence Interval Lower Upper p Value Hazard Ratio Lower Upper GENERAL THORACIC Age ( 60 vs 60 years) Gender (female vs male Side of resection (right vs left) Resected ribs ( 2vs 2) Pathology ADK vs SCC ADK vs others Tumor size ( 6vs cm) In-depth chest wall invasion P ST vs P P ST vs. P ST R Vessels invasion (yes vs no) Adjuvant radiotherapy (yes vs no) Type of resection (extrapleural vs en bloc) ADK adenocarcinoma; P pleura; P ST pleura soft tissues; P ST R pleura soft tissue ribs; SCC squamous cell carcinoma. control of the disease in N patients. However, our study, as well as most publications, sins by the absence of a uniform protocol employed in those patients [1, 4 6, 9, 13]. To conclude, the present results highlight several particular features of chest wall pt3 NSCLC patients. The disastrous impact of lymph node metastases on survival leads to questions of whether surgery is of any benefit in this subset of patients. The best surgical candidates are likely to be those with a N0 disease. In that way, en-bloc resection is strongly suggested to be the standard of surgical care, and adjuvant radiotherapy does not seem to be necessary if a complete resection has been achieved. For huge tumors, this report suggests that the role of perioperative chemotherapy needs further evaluation. References 1. Piehler JM, Pairolero PC, Weiland LH, Offord KP, Payne WS, Bernatz PE. Bronchogenic carcinoma with chest wall invasion: factors affecting survival following en bloc resection. Ann Thorac Surg 1982;34: McCaughan BC, Martini N, Bains MS, McCormack PM. Chest wall invasion in carcinoma of the lung. Therapeutic and prognostic implications. J Thorac Cardiovasc Surg 1985; 89: Albertucci M, DeMeester TR, Rothberg M, Hagen JA, Santoscoy R, Smyrk TC. Surgery and the management of peripheral lung tumors adherent to the parietal pleura. J Thorac Cardiovasc Surg 1992;103: Downey RJ, Martini N, Rusch VW, Bains MS, Korst RJ, Ginsberg RJ. Extent of chest wall invasion and survival in patients with lung cancer. Ann Thorac Surg 1999;68: Facciolo F, Cardillo G, Lopergolo M, Pallone G, Sera F, Martelli M. Chest wall invasion in non-small cell lung carcinoma: a rationale for en bloc resection. J Thorac Cardiovasc Surg 2001;121: Magdeleinat P, Alifano M, Benbrahem C, et al. Surgical treatment of lung cancer invading the chest wall: results and prognostic factors. Ann Thorac Surg 2001;71: Elia S, Griffo S, Gentile M, Costabile R, Ferrante G. Surgical treatment of lung cancer invading chest wall: a retrospective analysis of 110 patients. Eur J Cardiothorac Surg 2001;20: Chapelier A, Fadel E, Macchiarini P, et al. Factors affecting long-term survival after en-bloc resection of lung cancer invading the chest wall. Eur J Cardiothorac Surg 2000;18: Allen MS, Mathisen DJ, Grillo HC, Wain JC, Moncure AC, Hilgenberg AD. Bronchogenic carcinoma with chest wall invasion. Ann Thorac Surg 1991;51: Roviaro G, Varoli F, Grignani F, et al. Non-small cell lung cancer with chest wall invasion: evolution of surgical treatment and prognosis in the last 3 decades. Chest 2003;123: Burkhart HM, Allen MS, Nichols FC III, et al. Results of en bloc resection for bronchogenic carcinoma with chest wall invasion. J Thorac Cardiovasc Surg 2002;123: Casillas M, Paris F, Tarrazona V, Padilla J, Paniagua M, Galan G. Surgical treatment of lung carcinoma involving the chest wall. Eur J Cardiothorac Surg 1989;3: Pitz CC, Brutel de la Riviere A, Elbers HR, Westermann CJ, van den Bosch JM. Surgical treatment of 125 patients with non-small cell lung cancer and chest wall involvement. Thorax 1996;51:

9 2040 DODDOLI ET AL Ann Thorac Surg LUNG CANCER INVOLVING THE CHEST WALL 2005;80: Ribet M, al Nashawati G. Bronchial cancers invading the chest wall. Rev Mal Respir 1992;9: Carrel T, Nachbur B, Veraguth P. En bloc resection for bronchogenic carcinoma with chest wall invasion. Value of pre-operative radiotherapy. Eur J Cardiothorac Surg 1990;4: Yanagi S, Sugiura H, Morikawa T, et al. Tumor size does not have prognostic significance in stage Ia NSCLC. Anticancer Res 2000;20: Patz EF Jr, Rossi S, Harpole DH Jr, Herndon JE, Goodman PC. Correlation of tumor size and survival in patients with stage IA non-small cell lung cancer. Chest 2000;117: Padilla J, Calvo V, Penalver JC, et al. Survival and risk model for stage IB non-small cell lung cancer. Lung Cancer 2002; 36: Carbone E, Asamura H, Takei H, et al. T2 tumors larger than five centimeters in diameter can be upgraded to T3 in non-small cell lung cancer. J Thorac Cardiovasc Surg 2001; 122: Riquet M, Lang-Lazdunski L, Le Pimpec-Barthes F, et al. Characteristics and prognosis of resected T3 non-small cell lung cancer. Ann Thorac Surg 2002;73: Ramsey HE, Cliffton EE. Chest wall resection for primary carcinoma of the lung. Ann Surg 1968;167: De Perrot M, Licker M, Bouchardy C, Usel M, Robert J, Spiliopoulos A. Sex differences in presentation, management, and prognosis of patients with non-small cell lung carcinoma. J Thorac Cardiovasc Surg 2000;119: Ferguson MK, Wang J, Hoffman PC, et al. Sex-associated differences in survival of patients undergoing resection for lung cancer. Ann Thorac Surg 2000;69: Alexiou C, Onyeaka CV, Beggs D, et al. Do women live longer following lung resection for carcinoma? Eur J Cardiothorac Surg 2002;21: Canver CC, Memoli VA, Vanderveer PL, Dingivan CA, Mentzer RM Jr. Sex hormone receptors in non-small cell lung cancer in human beings. J Thorac Cardiovasc Surg 1994;108: Schreiber G, Fong KM, Peterson B, Johnson BE, O Briant KC, Bepler G. Smoking, gender, and survival association with allele loss for the LOH11B lung cancer region on chromosome 11. Cancer Epidemiol Biomark Prev 1997;6: INVITED COMMENTARY Doddoli and colleagues [1] have reported the largest series of patients with completely resected nonsmall cell lung cancer invading the chest wall. Their series is a retrospective analysis and it confirms the results of other large series in most respects. Because all of the patients in this series underwent complete (R0) resection, the main influence on overall survival was the presence or absence of lymph node metastases. T3N0M0 (stage IIB) patients had a median and 5-year survival of 19 months and 40%, respectively. Patients staged IIIA (T3N1M0 or T3N2M0) had a 12% 5-year survival (p 10 4 ). T3N0 patients did not benefit from adjuvant radiotherapy to the chest wall. Novel findings included the fact that based on their multivariate analysis stage IIIA patients seemed to benefit in terms of survival from adjuvant radiotherapy to the chest wall and mediastinum. The authors also noted that in the stage IIB subgroup of patients with tumor invasion limited to the parietal pleura, the survival rate of those patients undergoing en bloc chest wall resection was greater than that of patients undergoing extrapleural resection. This is a controversial finding not consistently supported in the literature. Certainly if there is any question of tumor invasion beyond the parietal pleura, en bloc resection of the chest wall should be performed. An unusual aspect of this series is the inclusion of patients with superior sulcus tumors. Superior sulcus tumors are usually not included in series of lung cancers invading the chest wall because they may have higher local recurrence rates, require a unique operative approach, and so forth. The authors justify the inclusion of these patients by saying that none of those included had Pancoast syndrome. Surely some of these patients had pain because all had T3 tumors, although they may not have had Horner s syndrome and muscle wasting. The best approach would have been for the authors to analyze these patients separately within the report or to at least tell us how many patients with superior sulcus tumors were included in their series. Walter J. Scott, MD Thoracic Surgical Oncology Fox Chase Cancer Center Suite C Cottman Avenue Philadelphia, PA w_scott@fccc.edu Reference 1. Doddoli C, D Journo B, Le Pimpec-Barthes F, et al. Lung cancer invading the chest wall: a plea for en-bloc resection but the need for new treatment strategies. Ann Thorac Surg 2005;80: by The Society of Thoracic Surgeons /05/$30.00 Published by Elsevier Inc doi: /j.athoracsur