Frequency and prognostic significance of isolated tumour cells in bone marrow of patients with non-small-cell lung cancer without overt metastases

Abstract

Background: Metastasis is generally looked on as a late event in the natural history of epithelial tumours. However, the poor prognosis of patients with apparently localised lung cancer indicates that micrometastases occur often before diagnosis of the primary tumour.

Methods: At primary surgery, disseminated tumour cells were detected immunocytochemically in bone marrow of 139 patients with non-small-cell lung carcinomas without evidence of distant metastases (pT(1-4)pN(1-2)M(0)). Tumour cells in bone-marrow aspirates were detected with monoclonal antibody CK2 against cytokeratin polypeptide 18. Patients were followed up for a median of 39 months (range 14-52) after surgery. 215 patients without epithelial cancer (ie, with benign epithelial tumours, non-epithelial neoplasms, or inflammatory diseases) acted as controls.

Findings: In 83 of 139 (59.7%) patients cytokeratin-positive cells were detected at frequencies of 1 in 100 000 to 1 in 1 000 000. Even without histopathological involvement of lymph nodes (pN(0)), tumour cells were found in 38 of 70 (54.3%) patients. 1 positive cell was found in each of 6 out of 215 controls. Surgical manipulation during primary tumour resection did not affect the frequency of these cells. In Cox's regression analyses, the presence of such cells was a significant and independent predictor for a later clinical relapse in node-negative patients (p=0.028).

Interpretation: Early dissemination of isolated tumour cells is a frequent and intrinsic characteristic of non-small-cell lung carcinomas. The finding of these cells may help to decide whether adjuvant systemic therapy is required for the individual patient.