[Isolated tumor cells in bone marrow predicts reduced survival in lymph node-negative non-small-cell lung cancer]

Abstract

Background: It became recently evident that isolated tumor cells undetectable by conventional tumor staging are frequently present in bone marrow of patients with apparently localized non-small cell lung cancer (NSCLC). The clinical relevance of this minimal hematogenous tumor cell dissemination is under vigorous debate.

Methods: For tumor cell detection in the bone marrow we used monoclonal antibody CK2 against the epithelial intermediate filament protein cytokeratin 18. The influence of a positive bone marrow finding on clinical outcome was studied in 139 patients with NSCLC postoperatively staged as pT1-4, pN0-2, M0, R0 after a median follow up of 66 months (48-74).

Findings: Cytokeratin-18-positive cells in bone marrow were demonstrated in 83 (59.7%) patients at the time of primary surgery and in 6 of 12 representative patients analyzed twice 3-18 months after surgery. In patients without histopathological lymph node metastases (pN0; n = 66) the occurrence of > or = 2 tumor cells in bone marrow at primary surgery was a strong and independent predictor for overall survival (p = 0.007) in univariate analysis. The multivariate analysis showed a 2.8 times increased risk for shorter survival in patients with disseminated tumor cells versus patients without such cells. Four of the six patients with a positive CK status after surgery developed a tumor recurrence 11-44 months after the operation, while in none of the patients with a negative bone marrow at all times intervals showed a tumor relapse.

Conclusions: Minimal residual bone marrow involvement is an independent prognostic factor for overall survival in patients with node-negative NSCLC, which may help to identify patients in need of an adjuvant systemic therapy. The postoperative persistence or re-appearance of tumor cells in bone marrow indicates that these are not only shredded cells but rather represent true micrometastasis.