Prognostic value and therapeutic consequences of vascular invasion in non-small cell lung carcinoma

Abstract

The prognostic relevance of blood vessel invasion (BVI) in non-small cell lung carcinoma (NSCLC) remains controversial, as is the question of whether its finding should influence therapeutic decisions after an R0 resection. One hundred and twelve cases of NSCLC were included in the study. All had been treated by potentially curative surgical resection of the primary tumor and systematic lymphadenectomy. In all cases, lymphatic metastatic spread was at its earliest stage and only one regional lymph node was involved, 27.0 ± 8.9 nodes per patient being examined histologically. Most of the cases were pT2 (75.9%) and pN1 (81.3%), and all were MX/M0 and R0. 62.5% were at stage IIB, 25.9% at stage IIIA, and 9.8% at stage IIA. BVI was found in 45.5% of the tumors (V1), and 18.8% exhibited both lymphatic invasion and BVI (L1V1). Local recurrence occurred in 10.7% of the patients, distant metastasis in 24.1%, and both forms of tumor progression simultaneously in a further 7.1%. Thus 31.2% of the patients developed distant metastases by hematogenous spread (to the brain, bones, lung, adrenal, and liver, in descending order of frequency), mostly within two years of surgery. Late metastasis is not typical of NSCLC. Adenocarcinomas showed a strong tendency to be associated with a poorer prognosis than squamous cell carcinomas, probably because of their more frequent involvement of blood vessels. Five-year survival (Kaplan–Meier method) was significantly lower in V1 cases (37.2%) than in V0 cases (56.0%; p = 0.0249).

Adjuvant mediastinal radiation in node-positive cases of NSCLC may prevent local recurrence but is unlikely to influence the development of distant metastases. The histological detection of BVI is of prognostic relevance and should be considered for inclusion in the staging criteria and indications for adjuvant chemotherapy.

Introduction

As many as 60–80% of non-small cell lung carcinomas (NSCLC) are already inoperable at the time of diagnosis [1], [2]. In stages IA–IIB, resection is still the treatment of choice [3]. Stage IA tumors (T1/N0) are associated with a 5-year survival of more than 70% [4], [5]. Lymph node status is often quoted as the most important prognostic factor [5], [6], [7], [8], [9], [10], [11], but other parameters, such as UICC stage, histology, grade, and residual tumor status (R classification), are also important prognostic factors [1], [3], [5], [11], [12], [13], [14]. However, it remains unclear whether intratumorous lymphatic invasion and/or blood vessel invasion (BVI) can be regarded as true prognostic factors [11], [15]. The aim of this study was to investigate the influence of early lymphatic tumor spread (only one regional lymph node positive) and BVI on the prognosis of patients with NSCLC, mainly in stages IIA–IIIA, and their possible consequences for the choice of treatment.