Heterogeneous prognosis and adjuvant chemotherapy in pathological stage I non-small cell lung cancer patients

Chia-Hsin Liu, Yi-Jen Peng, Hong-Hau Wang, Ying-Chieh Chen, Chen-Liang Tsai, Chih-Feng Chian, Tsai-Wang Huang, Chia-Hsin Liu, Yi-Jen Peng, Hong-Hau Wang, Ying-Chieh Chen, Chen-Liang Tsai, Chih-Feng Chian, Tsai-Wang Huang

Abstract

Background: Even after curative resection, the prognosis of pathological stage I non-small cell lung cancer (NSCLC) can be heterogeneous, and the use of adjuvant chemotherapy in these patients is controversial. We aimed to identify the prognostic factors and role of adjuvant chemotherapy in pathological stage I NSCLC.

Methods: We retrospectively analyzed the correlations between clinicopathological factors and survival in 179 patients with resected pathological stage I NSCLC.

Results: After a median follow-up of 93 months, overall and disease-free survival were not significantly different between pathological stage IA (n = 138) and IB (n = 41) patients. The prognosis of pathological stage I patients with poorly differentiated tumors was significantly worse than that of those with non-poorly differentiated tumors (P = 0.003). Multivariate analysis revealed that poor tumor differentiation was an independent factor for poor survival (hazard ratio = 6.889). A marginally significant survival benefit was observed in poorly differentiated pathological stage I patients who received adjuvant chemotherapy (P = 0.053). Pathological stage IA patients who received adjuvant chemotherapy had a worse prognosis than those who did not receive adjuvant chemotherapy (P < 0.001), whereas pathological stage IA patients with poorly differentiated tumors who received adjuvant chemotherapy had better survival than who did not receive adjuvant chemotherapy (P < 0.001).

Conclusions: Poor differentiation is an independent prognostic factor in pathological stage I NSCLC after surgical resection. Adjuvant chemotherapy may be beneficial in poorly differentiated pathological stage IA NSCLC patients.

Keywords: Adjuvant chemotherapy; neoplasm grading; non-small cell lung carcinoma; prognosis; tumor staging.

Figures

Figure 1
Figure 1
Representative histopathological features of non-small cell lung cancers. (a) Well-differentiated squamous cell carcinoma. (b) Moderately differentiated squamous cell carcinoma. (c) Poorly differentiated squamous cell carcinoma. (d) Well-differentiated adenocarcinoma. (e) Moderately differentiated adenocarcinoma. (f) Poorly differentiated adenocarcinoma.
Figure 2
Figure 2
(a) Overall survival and (b) disease-free survival in stage IA and stage IB patients. Stage: , 1A; , 1B; , 1A-censored; , 1B-censored.
Figure 3
Figure 3
Overall survival in stage I patients according to (a) tumor size (>4 cm vs. ≤4 cm), and (b) tumor differentiation (poor vs. non-poor). (a) Tumor size: , ≤4 cm; , >4 cm; , 1-censored; , 2-censored. (b) Tumor differentiation: , No-poor; , poor; , 1-censored; , 2-censored.
Figure 4
Figure 4
Overall survival in (a) patients with poor tumor differentiation, and (b) patients with non-poor tumor differentiation according to adjuvant chemotherapy administration. Chemotherapy: , No; , Yes; , 0-censored; , 1-censored.
Figure 5
Figure 5
Overall survival in (a) stage IA patients, and (b) stage IB patients, according to adjuvant chemotherapy administration. Chemotherapy: , No; , Yes; , 0-censored; , 1-censored.
Figure 6
Figure 6
Overall survival in (a) stage IA patients with poor tumor differentiation, and (b) stage IA patients with non-poor tumor differentiation according to adjuvant chemotherapy administration. Chemotherapy: , No; , Yes; , 0-censored; , 1-censored.

References

    1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statisticsCA Cancer J Clin61: CA Cancer J Clin. 2011;61:69–90. (Published erratum appears in 2011; 134)
    1. Devesa SS, Bray F, Vizcaino AP, Parkin DM. International lung cancer trends by histologic type: Male:female differences diminishing and adenocarcinoma rates rising. Int J Cancer. 2005;117:294–299.
    1. Morgensztern D, Ng SH, Gao F, Govindan R. Trends in stage distribution for patients with non-small cell lung cancer: A National Cancer Database survey. J Thorac Oncol. 2010;5:29–33.
    1. Datta D, Lahiri B. Preoperative evaluation of patients undergoing lung resection surgery. Chest. 2003;123:2096–2103.
    1. Goya T, Asamura H, Yoshimura H, et al. Prognosis of 6644 resected non-small cell lung cancers in Japan: A Japanese lung cancer registry study. Lung Cancer. 2005;50:227–234.
    1. Okada M, Nishio W, Sakamoto T, et al. Effect of histologic type and smoking status on interpretation of serum carcinoembryonic antigen value in non-small cell lung carcinoma. Ann Thorac Surg. 2004;78:1004–1009.
    1. Asamura H, Goya T, Koshiishi Y, et al. A Japanese Lung Cancer Registry study: Prognosis of 13,010 resected lung cancers. J Thorac Oncol. 2008;3:46–52.
    1. Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: A pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26:3552–3559.
    1. Arriagada R, Dunant A, Pignon JP, et al. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol. 2010;28:35–42.
    1. Travis WD, Brambilla E, Müller-Hermmelink HK, Harris CC, editors. Pathology & Genetics: Tumours of the Lung, Pleura, Thymus and Heart. Lyon: IARC Press; 2004.
    1. Goldstraw P, Crowley J, Chansky 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.
    1. Ou SH, Zell JA, Ziogas A, Anton-Culver H. Prognostic factors for survival of stage I nonsmall cell lung cancer patients: A population-based analysis of 19,702 stage I patients in the California Cancer Registry from 1989 to 2003. Cancer. 2007;110:1532–1541.
    1. Sun Z, Aubry MC, Deschamps C, et al. Histologic grade is an independent prognostic factor for survival in non-small cell lung cancer: An analysis of 5018 hospital- and 712 population-based cases. J Thorac Cardiovasc Surg. 2006;131:1014–1020.
    1. Ichinose Y, Yano T, Asoh H, Yokoyama H, Yoshino I, Katsuda Y. Prognostic factors obtained by a pathologic examination in completely resected non-small-cell lung cancer. An analysis in each pathologic stage. J Thorac Cardiovasc Surg. 1995;110:601–605.
    1. Kobayashi N, Toyooka S, Soh J, et al. Risk factors for recurrence and unfavorable prognosis in patients with stage I non-small cell lung cancer and a tumor diameter of 20 mm or less. J Thorac Oncol. 2007;2:808–812.
    1. Suzuki K, Nagai K, Yoshida J, et al. Conventional clinicopathologic prognostic factors in surgically resected nonsmall cell lung carcinoma. A comparison of prognostic factors for each pathologic TNM stage based on multivariate analyses. Cancer. 1999;86:1976–1984.
    1. Khan OA, Fitzgerald JJ, Field ML, et al. Histological determinants of survival in completely resected T1-2N1M0 nonsmall cell cancer of the lung. Ann Thorac Surg. 2004;77:1173–1178.
    1. Pelletier MP, Edwardes MD, Michel RP, Halwani F, Morin JE. Prognostic markers in resectable non-small cell lung cancer: A multivariate analysis. Can J Surg. 2001;44:180–188.
    1. Kozu Y, Maniwa T, Takahashi S, Isaka M, Ohde Y, Nakajima T. Risk factors for both recurrence and survival in patients with pathological stage I non-small-cell lung cancer. Eur J Cardiothorac Surg. 2013;44:e53–58.
    1. Ceppi P, Mudduluru G, Kumarswamy R, et al. Loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype in non-small cell lung cancer. Mol Cancer Res. 2010;8:1207–1216.
    1. Deng LL, Deng HB, Lu CL, et al. Mutations of EGFR or KRAS and expression of chemotherapy-related genes based on small biopsy samples in stage IIIB and IV inoperable non-small cell lung cancer. J Cancer Res Clin Oncol. 2014;140:2097–2105.
    1. Hamada C, Tsuboi M, Ohta M, et al. Effect of postoperative adjuvant chemotherapy with tegafur-uracil on survival in patients with stage IA non-small cell lung cancer: An exploratory analysis from a meta-analysis of six randomized controlled trials. J Thorac Oncol. 2009;4:1511–1516.
    1. Strauss GM, Herndon JE, 2nd, Maddaus MA, et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008;26:5043–5051.
    1. Park SY, Lee JG, Kim J, et al. Efficacy of platinum-based adjuvant chemotherapy in T2aN0 stage IB non-small cell lung cancer. J Cardiothorac Surg. 2013;8:151.

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