Asian Cardiovasc Thorac Ann 2006;14:30-34
© 2006 Asia Publishing EXchange Ltd
Relationship of Tumor Size to Survival in Patients With pT2N0 Lung Cancer
Ryuichi Suemitsu, MD,
Hitoshi Ueda, MD,
Yasunori Shikada, MD1,
Kaoru Ondo, MD,
Ichiro Yoshino, MD1,
Yoshihiko Maehara, MD1
Department of Thoracic Surgery, Matsuyama Red Cross Hospital, Matsuyama, Japan
1 Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
For reprint information contact: Ryuichi Suemitsu, MD Tel: 81 89 924 1111 Fax: 81 89 922 6892 Email: sue{at}matsuyama.jrc.or.jp, Department of Thoracic Surgery, Matsuyama Red Cross Hospital, 1 Bunkyoh-cho, Matsuyama 790-8524, Japan.
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ABSTRACT
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Lung cancer extending beyond 3 cm in diameter without lymph node or distant metastasis is defined as T2. The purpose of this study was to analyze the prognosis based on tumor size for patients with resected T2N0M0 non-small cell lung cancer. The 268 patients who underwent complete resection of a lung tumor > 3 cm in diameter were reviewed retrospectively. They were divided into 3 groups based on tumor size: 3–5 cm, > 5–7 cm, and > 7 cm. There were significant differences in the 5-year survival rates of 61.4%, 47.9%, and 21.9% in each group, respectively. In the two subgroups with tumor sizes 3–4 cm and > 4 cm, the 5-year survival was 63.8% and 48.1%, respectively. Tumors > 4 cm in diameter indicate a poor long-term prognosis.
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INTRODUCTION
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Lung cancer is increasing worldwide and since 1998, it has been the most common cause of cancer death among Japanese. Lung cancer is an aggressive carcinoma with a poor outcome. In 1997, Mountain1 refined the TNM staging system of lung cancer. The T2 category includes a tumor of more than 3 cm, visceral pleura involvement, tumor involvement of other endothoracic structures such as the proximal bronchus, and atelectasis or pneumonitis due to tumor involvement. Since 1974, 3 cm has been regarded as the prognostic threshold in the staging of lung cancer.2 The T2 lung cancer that involves other organs or the pleura might be considered to have poor prognosis, however, there has been much discussion regarding prognosis in relation to tumor size and the issue is still in dispute.3 Generally, as tumor size increases, the prognosis of lung cancer patients worsens.4–9 In this study, we retrospectively analyzed the survival of patients with completely resected T2 lung cancer according to tumor size.
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PATIENTS AND METHODS
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There were 303 patients with stage IB lung cancer treated by pulmonary resection and lymph node dissection in our department from June 1974 to February 2002. The 268 who underwent complete resection and whose tumors did not involve pleural or other endothoracic structures were included in this study. Disease was staged postsurgically according to the TNM criteria of the International System for Staging Lung Cancer.1 Initially, the patients were divided into three groups according to tumor size: group 1 was 191 patients with a tumor of 3–5 cm in diameter, group 2 was 58 patients with a tumor > 5–7 cm, and group 3 was 19 patients with a tumor > 7 cm. The patients were then divided into subgroups based on tumor sizes with 10 mm increments: 133 patients with a tumor of 31 to 40 mm, 60 patients with a tumor of 41 to 50 mm, and 75 patients with a tumor of more than 50 mm. There were 191 males (71.3%) and 77 females (28.7%), their mean age at operation was 65.6 ± 9.75 years. Histological typing was carried out according to the World Health Organization histologic classification.10 The histological types and operative approaches are shown in Table 1
. The surgical-pathological size was obtained by measuring the greatest diameter of the fresh surgical specimen. Tumor sizes ranged from 31 to 223 mm (mean, 46.8 ± 18.5 mm). Surgical-pathologic stage N0 was assigned when there was no lymph node involvement after systematic nodal dissection was performed.
A follow-up examination was usually carried out every 2 months for the first 2 years, and every 3 to 4 months thereafter. The follow-up included a physical examination, complete blood count, blood chemistry, and chest radiography. Although a few patients routinely underwent screening by CT or radionuclide bone scanning once or twice per year after their operation, the majority underwent CT or a radionuclide bone scan only when symptoms of recurrence appeared. Recurrent disease was confirmed by biopsy if clinically feasible. In patients for whom this was not feasible, radiographic evidence (radiography, CT, or radionuclide scan) was accepted.
The chi-squared test and Student’s t test were used to compare the data. Survival curves were constructed using the Kaplan-Meier method, and the Mantel-Cox test was used to analyze the equality of the survival. A p value of less than 0.05 was considered significant.
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RESULTS
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No significant difference was observed in the distribution of sex, age, histology, and surgical treatments among the 3 main groups (Table 1
). The overall survival of the 268 patients was 55.8% at 5 years (Figure 1). The 5-year and 10-year survival rates of the 3 groups were: group 1, 61.4% and 41.6%; group 2, 47.9% and 29.6%; group 3, 21.9% and 14.6%. The differences between groups were significant ( p < 0.0001; Figure 2), especially between group 1 and the other 2 groups (Table 2). The 3-year and 5-year freedom from recurrence rates of the 3 main groups are also shown in Table 2; these were significantly different ( p = 0.0002). The 5-year and 10-year survival rates of the subgroups based on tumor size at 10 mm increments were: 3–4 cm, 63.8% and 47.1%; > 4–5 cm, 57.8% and 30.0%; > 5 cm, 39.8% and 25.3%. These 3 subgroups were significantly different ( p = 0.0007; Figure 3).
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Figure 1. Survival curve of 268 patients with completely resected stage IB cancer. Five-year survival was 55.8%, 10-year survival was 37.2%.
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Figure 2. Survival curves according to tumor size of patients with completely resected stage IB lung cancer. Comparison between groups: p < 0.0001. Five-year survival rates for the 3–5 cm group, > 5 – 7 cm group, and > 7 cm group were 61.4%, 47.9%, and 21.9%, respectively.
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Figure 3. Survival curves of patients with tumors of 3–4 cm, > 4 – 5 cm, and > 5 cm. Comparison between groups: p = 0.0007. Five-year survival rates for the 3–4 cm group, > 4 – 5 cm group, and > 5 cm group were 63.8%, 57.8%, and 39.8%, respectively.
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Because of the small number of cases, the survival rate of patients with adenosquamous cell carcinoma was not analyzed. No significant difference was observed in the distribution of histology among the 3 groups ( p = 0.4558). The survival curves according to the histology are shown in Figure 4. There was a significant difference in survival between adenocarcinoma and squamous cell carcinoma ( p = 0.0486). In 192 patients over 60-years old, the 5-year and 10-year survival rates were significantly lower than those of younger patients (Table 3).
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Figure 4. Survival curves of 264 patients according to histological type. Adenocarcinoma vs. squamous cell carcinoma, p = 0.0486; squamous cell carcinoma vs. large cell carcinoma, p = 0.0792; adenocarcinoma vs. large cell carcinoma, p = 0.6404. Five-year survival rates for adenocarcinoma, large cell carcinoma, and squamous cell carcinoma were 58.0%, 53.9%, and 52.8%, respectively.
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DISCUSSION
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Stage IB non-small cell lung cancer is usually defined as a resectable disease, with a good prognosis being achieved by complete resection. However, patients who experience metastasis or recurrence in the early postoperative period have a poor prognosis. In particular, patients with adenocarcinoma are more prone to experience metastasis compared to those with squamous cell carcinoma (SCC). Post- and/or preoperative chemotherapy is often needed in progressive non-small cell lung cancer, such as stage III.11–12 In contrast to progressive disease, stage I non-small cell lung cancer responds to non-adjuvant therapy after surgery. However, Wada and colleagues13 reported that adjuvant chemotherapy after surgery improved the prognosis in pathological stage I patients. In 2003, the American Society of Clinical Oncology reported that a randomized phase III trial of adjuvant chemotherapy with uracil and tegafur for completely resected pathological stage IB adenocarcinoma of the lung showed significantly improved survival. These reports indicate that some non-small cell lung cancers in stage I need neoadjuvant chemotherapy.
One report stated that T2N0 lung cancer had a good prognosis; however, for T2 tumors above 3 cm, as defined by the WHO, a giant tumor with non-lymph node metastasis and non-distant metastasis should be contained within the T2 criteria.1 Several institutions have reported that the larger the tumor size, the worse the prognosis.4–9 In this study, survival data were very similar to those reported by other institutions.1,8 The prognosis became significantly worse with increasing tumor size. In addition, the disease-free interval after surgical treatment was shorter with increasing tumor size and correlated with the prognosis. The 5-year disease-free interval rates for the 3–5 cm, > 5–7 cm, and > 7 cm groups were 58.7%, 30.9%, and 27.6%, respectively. Postoperative recurrence and/or metastasis increased according to tumor size. We believe that larger tumors produce more tumor cell stimulating factors and cytokines, such as transforming growth factor and interleukin-6, hence micrometastasis increases according to tumor size, and is one of the reasons for poor prognosis.
There were significant differences in survival among the 3 main groups in this study. Therefore, survival rates were further analyzed by dividing the subjects into 3 subgroups. The survival curves of these three subgroups indicated a prognostic threshold which was investigated by analyzing the survival rates of the 133 patients with tumor size 3–4 cm and the 135 patients with tumors > 4 cm. The results show that lung cancer patients have poor prognoses when the tumor is over 4 cm. The 5-year survival of stage IA surgically resected non-small cell lung cancer patients in this institution during the same period was 75.6%. This was significantly higher than the 63.8% survival rate of the 3–4 cm subgroup ( p = 0.0270).
Histological types were mainly adenocarcinoma and SCC, accounting for 91.8% of the 268 patients. Among the 3 tumor size groups, there was no difference in the distribution of histological type. The survival rate of SCC patients was the lowest. Our previous study on the prognosis of patients undergoing blood transfusion associated with pneumonectomy showed lower survival rates in SCC patients than in those with adenocarcinoma. Various types of carcinomas express different biological behaviors, and our results reflect the specific biological character of lung cancer. Elderly patients showed a statistically worse prognosis, but no correlation between age and tumor size was apparent in our study, in contrast to results reported by another facility.14 Our finding that stage IB non-small lung cancer patients with tumors over 4 cm had a poor prognosis indicates that this group need adjuvant therapy.
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REFERENCES
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- Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997;111:1710–7.[Abstract/Free Full Text]
- Mountain CF, Carr DT, Anderson WA. A system for the clinical staging of lung cancer. Am J Roentgenol Radium Ther Nucl Med 1974;120:130–8.[Medline]
- Kang JH, Kim KD, Chung KY. Prognostic value of visceral pleura invasion in non-small cell lung cancer. Eur J Cardiothorac Surg 2003;23:865–9.[Abstract/Free Full Text]
- 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;117:1568–71.[Abstract/Free Full Text]
- Lopez-Encuentra A, Duque-Medina JL, Rami-Porta R, de la Camara AG, Ferrando P; Bronchogenic Carcinoma Co-operative Group of the Spanish Society of Pneumology and Thoracic Surgery. Staging in lung cancer: is 3 cm a prognostic threshold in pathologic stage I non-small cell lung cancer? A multicenter study of 1,020 patients. Chest 2002;121:1515–20.[Abstract/Free Full Text]
- Sakao Y, Sakuragi T, Natsuaki M, Itoh T. Clinicopathological analysis of prognostic factors in clinical IA peripheral adenocarcinoma of the lung. Ann Thorac Surg 2003;75:1113–7.[Abstract/Free Full Text]
- Gajra A, Newman N, Gamble GP, Abraham NZ, Kohman LJ, Graziano SL. Impact of tumor size on survival in stage IA non-small cell lung cancer: a case for subdividing stage IA disease. Lung Cancer 2003;42:51–7.[Medline]
- Padilla J, Calvo V, Penalver JC, Zarza AG, Pastor J, Blasco E, et al. Survival and risk model for stage IB non-small cell lung cancer. Lung Cancer 2002;36:43–8.[Medline]
- Carbone E, Asamura H, Takei H, Kondo H, Suzuki K, Miyaoka E, 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;122:907–12.[Abstract/Free Full Text]
- Travis WD, Colby TV, Corrin B, Shimosato Y, Brambilla E. In collaboration with Sobin LH and pathologists from 14 countries. World Health Organization international histological classification of tumours. Histological typing of lung and pleural tumours. 3rd ed. Berlin: Springer-Verlag, 1999.
- Bedini AV, Tavecchio L, Palazzi M. Surgical results of maximal local-regional treatment (cisplatin-enhanced high-dose radiotherapy and adjuvant surgery) in initially non-resectable stage III lung cancer. Lung Cancer 2002;35:271–7.[Medline]
- Roth JA, Fossella F, Komaki R, Ryan MB, Putnam JB Jr, Lee JS, et al. A randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. J Natl Cancer Inst 1994;86:673–80.[Abstract/Free Full Text]
- Wada H, Miyahara R, Tanaka F, Hitomi S. Postoperative adjuvant chemotherapy with PVM (Cisplatin + Vindesine + Mitomycin C) and UFT (Uracil + Tegaful) in resected stage I-II NSCLC (non-small cell lung cancer): a randomized clinical trial. West Japan Study Group for lung cancer surgery (WJSG). Eur J Cardiothorac Surg 1999;15:438–43.[Abstract/Free Full Text]
- Yamamoto K, Padilla Alarcon J, Calvo Medina V, Garcia-Zarza A, Pastor Guillen J, Blasco Armengod E, et al. Surgical results of stage I non-small cell lung cancer: comparison between elderly and younger patients. Eur J Cardiothorac Surg 2003;23:21–5.[Abstract/Free Full Text]
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ABSTRACT
INTRODUCTION
