Stage IA non-small cell lung cancer: Vessel invasion is a poor prognostic factor and a new target of adjuvant chemotherapy
Introduction
Recent advances in diagnostic imaging have increased the number of patients diagnosed with stage IA lung cancer. Histopathological and imaging studies of small size lung cancer strongly indicate the existence of good prognostic groups in stage IA non-small cell lung cancer (NSCLC) [1]. However, the overall 5-year survival of stage IA NSCLC still ranges from 66 to 85%, which indicates the existence of poor prognostic group [2], [3].
Stage IA NSCLC is sub-divided according to poor prognostic factors such as smoking history, serum level of carcinoembryonic antigen (CEA), extent of operation, tumour size, and vessel invasion (Vi) [4], [5], [6], [7], [8], [9]. Vi, which includes lymphatic or blood vessel invasion, is considered a useful predictor of survival in NSCLC. In a study of T1 N0 M0 adenocarcinomas and bronchioloalveolar carcinomas of the lung, Goldstain and colleagues demonstrated that the nonpulmonary metastasis-free survival advantage of patients without Vi was significant; 78% of patients were disease-free at 5 years when Vi was absent compared with only 35% when Vi was present [8].
Since 2004, clinical research studies have established the efficacy of adjuvant chemotherapy on post-operative patients with stage IB to IIIA NSCLC [10], [11], [12]. On the other hand, the trial of adjuvant chemotherapy on patients with stage IA NSCLC could not detect significant improvement of survival [11]. However, the seminal prospective study of Kato et al. [11] showed that treatment with uracil-tegafur, which has anti-vascular endothelial growth factor (VEGF) effect [13], tended to improve the survival rate of patients with a tumour measuring 2–3 cm in diameter. Because, Vi correlates with VEGF expression in lung cancer [14], we speculated that uracil-tegafur chemotherapy could improve survival of patients with surgically resected Vi-stage IA NSCLC.
The objectives of the present study were to assess whether Vi is a valuable prognostic criterion that can be used to sub-divide patients with surgically resected stage IA NSCLC, and to evaluate the effect of adjuvant chemotherapy of oral uracil-tegafur on stage IA Vi group.
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Patients
This retrospective study included 322 patients (178 male and 144 female) with pathological stage IA NSCLC who underwent surgical resection at Oita Prefectural Hospital between February 1978 and March 2005. The age distribution ranged from 41 to 88 years (median, 67 years). None of the patients received radio- or chemotherapy preoperatively. The clinical records of these patients were reviewed to obtain routine demographic information and confirm accurate pathological staging. The records of
Results
Vi was identified in 85 patients (26.4%; Vi group) among 322 patients with stage IA NSCLC. The overall 5-year survival rates were 89.6% for the non-Vi group (n = 237) and 71.8% for the Vi group (Fig. 1). The difference between the two groups was significant (P < 0.001).
The associations between Vi and various clinicopathological prognostic factors are shown in Table 1. Chi-square analysis showed the proportion of patients with Vi was significantly higher in patients with high serum CEA level (>5
Discussion
The aim of the present study was to determine whether vessel invasion (Vi) is an independent prognostic factor in patients with surgically resected stage IA NSCLC, and whether adjuvant chemotherapy could improve the survival of the poor prognostic group.
Our results clearly showed that Vi is a poor prognostic factor in patients with surgically resected stage IA NSCLC. We showed that overall 5-year survival rate of Vi group was significantly lower than that of non-Vi group. Both lymphatic and
Conclusion
Our data point to the efficacy of adjuvant chemotherapy in the poor prognostic group of stage IA NSCLC. We focused on Vi as a profitable prognostic factor, which can be clearly used to sub-divide patients with stage IA NSCLC. The prognosis of patients with surgically resected Vi-stage IA NSCLC was similar to that of patients with stage IB NSCLC. Uracil-tegafur-based adjuvant chemotherapy significantly improved prognosis of patients with Vi-stage IA NSCLC possibly based on high sensitivity. A
Conflicts of interest
None declared.
Acknowledgements
We thank Drs. Yoshitaka Uchiyama and Norio Yamaoka for their effort in data assembly and invaluable assistance.
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