Prognostic significance of tumoral angiogenesis in completely resected late stage lung carcinoma (stage IIIA-N2). Impact of adjuvant therapies in a subset of patients at high risk of recurrence.

Abstract

Angiogenesis plays a critical role in human tumor growth and metastasis. Microvessel count (MC), as a measure of tumor angiogenesis, has been significantly correlated with metastatic disease in cutaneous, mammary, prostatic, head and neck, and early stage lung carcinoma. Ninety-six consecutive patients affected by T1-3N2MO nonsmall cell lung carcinoma (NSCLC), who underwent radical surgery between March 1991 and March 1995 (in many cases followed by adjuvant therapies) were prospectively investigated to assess the prognostic significance of both traditional and new biologic parameters like proliferative activity, blood vessel invasion by tumoral cells, and neovascularization (estimated by the MC). With a median follow-up of 24 months, the projected 3-year survival was 42.1%. Forty-eight of the patients (50%) had already experienced a local (n=14) or systemic (n=34) relapse. The extent of resection (lobectomy vs. pneumonectomy; P=0.0045), the number of mediastinal lymph node levels (single vs. multiple; P=0.014), and the MC (on a X200 field; P=0.015) correlated significantly with metastatic disease. By univariate analysis, significant predictors of survival were: the extent of surgery (P=0.03), adjuvant therapy (P=0.05), and MC (< or = vs. > cut-off; P=0.00076). On multivariate analysis, however, only the MC (P=0.02) retained its level of prognostic significance. Our results provide evidence that neovascularization, estimated by the MC, can predict metastatic disease and survival in patients with completely resected T1-3N2M0 NSCLC, and may also be useful in patient selection for effective adjuvant treatment.