MODE OF SPREAD IN THE EARLY PHASE OF LYMPHATIC METASTASIS IN NON-SMALL-CELL LUNG-CANCER - SIGNIFICANCE OF NODAL MICROMETASTASIS

The impact of lymphatic micrometastases on prognosis of non-small-cell lung cancer has not been clearly established. We therefore prospectiv ely assessed the frequency, mode of mediastinal spread, and prognostic significance of lymphatic micrometastases in lymph nodes of 93 patien ts with completely resected non-small-cell lung cancer staged as pT1 t o pT4 pN0 and pN1 by conventional histopathologic techniques, Frozen t issue sections from 471 lymph nodes that were staged as free of metast ases by routine histopathologic examination mere screened for micromet astases by the alkaline phosphatase-antialkaline phosphatase immunosta ining technique with the monoclonal antibody Ber-Ep-4. Twenty of 73 pa tients (27.4%) with disease staged as pN0 and nine of 20 patients (45. 0%) with disease staged as pN1 had nodal micrometastases. Eight of 17 patients with upper lobe primary tumors and five of 12 patients with l ower lobe primary tumors exhibited skip micrometastases. Mean relapse- free survival nas significantly increased in patients with pN0 disease without micrometastases (41.1 vs 29 months, p = 0.0081). In patients with pN1 disease, mean relapse-free and cancer-related survivals were also significantly increased if no micrometastases were found (34.8 an d 38.2 months vs 18 and 23.5 months, p = 0.0157 and p = 0.0094), Patie nts with disease staged as pN0 and pN1 with micrometastases revealed n o difference in cancer-related survival compared with a control popula tion of patients with disease staged as pN2. The mode of spread was er ratic. The prognosis of patients after upstaging of pN0 and pN1 diseas e according to results of immunohistochemical staining correlated stro ngly with the prognosis of patients whose disease was staged at the hi gher stages by conventional histopathologic examination. These finding s could represent a new indication for adjuvant therapy, supporting ex tensive lymph node sampling for staging purposes.