FREQUENCY AND PROGNOSTIC-SIGNIFICANCE OF ISOLATED TUMOR-CELLS IN BONE-MARROW OF PATIENTS WITH NON-SMALL-CELL LUNG-CANCER WITHOUT OVERT METASTASES

Background Metastasis is generally looked on as a late event in the na tural history of epithelial tumours. However, the poor prognosis of pa tients with apparently localised lung cancer indicates that micrometas tases occur often before diagnosis of the primary tumour. Methods At p rimary surgery, disseminated tumour cells were detected immunocytochem ically in bone marrow of 139 patients with non-small-cell lung carcino mas without evidence of distant metastases (pT(1-4)pN(1-2)M(0)). Tumou r cells in bone-marrow aspirates were detected with monoclonal antibod y CK2 against cytokeratin polypeptide 18. Patients were followed up fo r a median of 39 months (range 14-52) after surgery. 215 patients with out epithelial cancer (ie, with benign epithelial tumours, nonepitheli al neoplasms, or inflammatory diseases) acted as controls. Findings In 83 of 139 (59.7%) patients cytokeratin-positive cells were detected a t frequencies of 1 in 100 000 to 1 in 1 000 000. Even without histopat hological 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 o ut of 215 controls. Surgical manipulation during primary tumour resect ion did not affect the frequency of these cells. In Cox's regression a nalyses, 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 carcinom as. The finding of these cells may help to decide whether adjuvant sys temic therapy is required for the individual patient.