Prognostic Factors in Resected T3 Non-Small Cell Lung Carcinoma: Perineural Invasion as a New Prognostic Factor

Abstract

Background: Currently the best prognostic indicator for resected non-small cell lung cancer (NSCLC) is the TNM stage. Moreover, certain histopathological properties of the tumor (such as lymphatic, vascular and perineural invasion) can help to predict the survival of the patients. Patients and Methods: Between 1997 and 2004, the results of surgical treatment were retrospectively analyzed for 153 patients with T3 non-small cell lung cancer. One hundred and twenty-four of them had had complete (R0) resections, and 29 had had incomplete (R1) resections. The prognostic factors evaluated by univariate and multivariate analysis were: type of resection; N status; subgroup of pT3; effect of adjuvant therapy; tumor size; histological type; tumor differentiation; lymphatic invasion; vascular invasion; and perineural invasion. Results: The overall 5-year survival rate was 32 % in R0 patients, and 8 % in R1 patients (p = 0.0002). The presence of N2 disease, vascular invasion, and perineural invasion were found to be significant prognostic indicators in univariate analysis (p = 0.0058, p = 0.033, and p = 0.0058, respectively). Among these indicators, N2 disease and perineural invasion were also found to be significant prognostic factors in multivariate analyses (p = 0.013, and p = 0.003, respectively). Conclusions: Incomplete resection, N2 disease, vascular and perineural invasion were found to be prognostic indicators for the survival of T3 NSCLC patients. Of these indicators, perineural invasion was found to be the strongest predictor of poor prognosis and independently affected the patients' survival.

Key words

NSCLC - T3 - vascular invasion - perineural invasion

References

• 1 Mountain C F. Revisions in the international system for staging lung cancer.  Chest. 1997;  111 1710-1717
• 2 Fujisawa T, Yamaguchi Y, Saitoh Y, Hiroshima K, Ohwada H. Blood and lymphatic vessel invasion as prognostic factors for patients with primary resected non-small cell carcinoma of the lung with intrapulmonary metastases.  Cancer. 1995;  76 2464-2470
• 3 Mountain C F. New prognostic factors in lung cancer. Biologic prophets of cancer cell aggression.  Chest. 1995;  108 246-254
• 4 O'Byrne K J, Cox G, Swinson D, Richardson D, Edwards J G, Lolljee J, Andi A, Koukourakis M I, Giatromanolaki A, Gatter K, Harris A L, Waller D, Jones J L. Towards a biological staging model for operable non-small cell lung cancer.  Lung Cancer. 2001;  34 (Suppl 2) S83-S89
• 5 Fu X L, Zhu X Z, Shi D R, Xiu L Z, Wang L J, Zhao S, Qian H, Lu H F, Xiang Y B, Jiang G L. Study of prognostic predictors for non-small cell lung cancer.  Lung Cancer. 1999;  23 143-152
• 6 Rigau V, Molina T J, Chaffaud C, Huchon G, Audouin J, Chevret S, Brechot J M. Blood vessel invasion in resected non small cell lung carcinomas is predictive of metastatic occurrence.  Lung Cancer. 2002;  38 169-176
• 7 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
• 8 Suzuki K, Nagai K, Yoshida J, Nishimura M, Takahashi K, Yokose T, Nishiwaki Y. Conventional clinicopathologic prognostic factors in surgically resected non-small cell lung carcinoma. A comparison of prognostic factors for each pathologic TNM stage based on multivariate analyses.  Cancer. 1999;  86 1976-1984
• 9 Roberts T E, Hasleton P S, Musgrove C, Swindell R, Lawson R AM. Vascular invasion in non-small cell lung carcinoma.  J Clin Pathol. 1992;  45 591-593
• 10 Shields T W. Prognostic significance of parenchymal lymphatic invasion and blood vessel invasion in carcinoma of the lung.  Surg Gynecol Obstet. 1983;  157 185-190
• 11 Goepfert H, Dichtel W J, Medina J E, Lindberg R D, Luna M D. Perineural invasion in squamous cell skin carcinoma of the head and neck.  Am J Surg. 1984;  148 542-547
• 12 Brechot J M, Chevret S, Charpentier M C, Appere de Vecchi C, Capron F, Prudent J, Rochemaure J, Chastang C. Blood vessel and lymphatic vessel invasion in resected non-small cell lung carcinoma. Correlation with TNM stage and disease free and overall survival.  Cancer. 1996;  78 2111-2118
• 13 Ruffini E, Rena O, Oliaro A, Filosso P L, Bongiovanni M, Arslanian A, Papalia E, Maggi G. Lung tumors with mixed histologic pattern. Clinico-pathologic characteristics and prognostic significance.  Eur J Cardiothorac Surg. 2002;  22 701-707
• 14 Sayar A, Turna A, Solak O, Kilicgun A, Urer N, Gurses A. Non-anatomic prognostic factors in resected non-small cell lung carcinoma: the importance of perineural invasion as a new prognostic marker.  Ann Thorac Surg. 2004;  77 421-425
• 15 World Health Organization .Histological Typing of Lung Tumors. 3rd edn. World Health Organization. Berlin, Heidelberg; Springer Verlag 1999
• 16 Pitz C C, Brutel de la Riviere A, Elbers H R, Westermann C J, van den Bosch J M. Results of resection of T3 non-small cell lung cancer invading the mediastinum or main bronchus.  Ann Thorac Surg. 1996;  62 1016-1020
• 17 Downey R J, Martini N, Rusch V W, Bains M S, Korst R J, Ginsberg R J. Extent of chest wall invasion and survival in patients with lung cancer.  Ann Thorac Surg. 1999;  68 188-193
• 18 Riquet M, Lang-Lazdunski L, Le Pimec-Barthes F. Characteristics and prognosis of resected T3 non-small cell lung cancer.  Ann Thorac Surg. 2002;  73 253-258
• 19 Nakahashi H, Yasumoto K, Sugimachi M. Results of surgical treatment of patients with T3 non-small cell lung cancer.  Ann Thorac Surg. 1996;  61 273-274
• 20 Ghiribelli C, Voltolini L, Paladini P, Luzzi L, Di Bisceglie M, Gotti G. Treatment and survival after lung resection for non-small cell lung cancer in patients with microscopic residual disease at the bronchial stump.  Eur J Cardiothorac Surg. 1999;  16 555-559
• 21 Fu X L, Jiang G L, Wang L J, Qian H, Fu S, Yie M. Discussion of prognostic factors in squamous cell carcinoma and adenocarcinoma of lung treated non-surgically.  China Oncol. 1996;  6 199-202
• 22 Cicero J L, Ponn R B, Daly D T. Surgical treatment of non-small cell lung cancer. Shields TW General Thoracic Surgery. 5th ed. Philadelphia; Lippincott, Williams, Wilkins 2000 99: 1311-1341
• 23 Tanaka F, Yanagihara K, Otake Y, Yamada T, Shoji T, Miyahara R, Inui K, Wada H. Prognostic factors in patients with resected pathologic (p-) T1-2N1M0 non-small cell lung cancer (NSCLC).  Eur J Cardiothorac Surg. 2001;  19 555-561
• 24 Kessler R, Gasser B, Massard G, Roeslin N, Meyer P, Wihlm J M, Morand G. Blood vessel invasion is a major prognostic factor in resected non-small cell lung cancer.  Ann Thorac Surg. 1996;  62 1489-1493
• 25 Cote R J, Beattie E J, Chaiwun B, Shi S R, Harvey J, Chen S C, Sherrod A E, Groshen S, Taylor C R. Detection of occult bone marrow micrometastases in patients with operable lung carcinoma.  Ann Surg. 1995;  222 415-423