DOES THE ASSESSMENT OF SERUM MARKERS IN PATIENTS WITH LUNG-CANCER AIDIN THE CLINICAL DECISION-MAKING PROCESS

This survey describes potential clinical applications of the tumour ma rkers CYFRA 21-1, SCC antigen, NSE, and CEA in patients with lung canc er. Due to the rather low prevalence of bronchogenic carcinoma in the general public and the limited diagnostic accuracy, currently availabl e tumour markers are unsuitable for the screening of asymptomatic indi viduals. All studies performed so far in patients with histologically confirmed NSCLC, agree that the best performance characteristics, in t erms of sensitivity and specificity, were obtained with the CYFRA 21-1 test (sensitivity: 40-66%, specificity: 95% versus patients with beni gn pulmonary disorders) while NSE was found to be the marker of first choice in patients with SCLC (sensitivity: 77-85%). For diagnostic pur pose, the value of tumour markers must be compared with the efficiency of standard clinical methods including imaging techniques and cytopat hological examinations (detection rates: sputum cytology: 40-70%, biop sy at bronchoscopy in central tumours: 95-98%, biopsy at bronchoscopy + bronchial washing + thin needle aspiration in peripheral tumours: 85 %). These figures show that the diagnostic yield of cytopathological e xaminations by far exceeds that of tumour markers. In addition, these investigations supply with histology and give informations on the T-st age (bronchoscopy). Tumour markers, however, may be used for diagnosis in advanced stages in which patients are very often not eligible for extensive investigations due to their performance status. In the diffe rential diagnosis between NSCLC and SCLC a combination of CYFRA 21-1 a nd NSE was claimed to be helpful. It was demonstrated that 97% of pati ents could be correctly classified. NSE was shown to be useful to dist inguish SCLC from malignant lymphoma, both the Hodgkin's (rate of fals e-positive elevations: 6.5%) and the non-Hodgkin's (rate of false posi tive elevations: 22.4%) types. By applying a cut-off point of NSE assa ys of 21.9 ng/ml corresponding to a 95% specificity versus the lymphom a group, SCLC is still indicated by elevated NSE levels with a sensiti vity of 57.7%. Although a positive correlation of marker concentration s with increasing anatomical tumour extent could be demonstrated, the markers cannot be used for staging purposes due to a considerable over lap of marker levels between the individual stage. CYFRA 21-1 was show n to be unable to differentiate between operable (TNM I-IIIa) and inop erable (TNM IIIb/IV) NSCLC patients. The latter were identified with a detection rate of only 17% by the CYFRA 21-1 test (specificity 95% ve rsus operable patients, cut-off point 20 ng/ml). Pretreatment-measured tumour markers, in particular CYFRA 21-1, were shown to provide progn ostic information for the overall survival. The negative prognostic ef fect of CYFRA-21-1 was independent of classical prognostic markers suc h as performance status and tumour extent. There are several potential applications of serially-assessed tumour markers for disease monitori ng of patients under therapy. In SCLC, increasing NSE levels within th e remission phase were demonstrated to be strongly suggestive of tumou r recurrence. This finding should give rise to further diagnostic proc edures. NSE, however, was not able to differentiate between partial an d complete remission since, in both cases, NSE levels dropped to the n ormal range; thus, NSE cannot replace clinical response evaluations. I n NSCLC, it was found that curative surgery resulted in a significant drop of preoperatively elevated CYFRA 21-1 or SCC antigen levels down to the normal range. Although rising SCC antigen levels in the postope rative surveillance of patients with squamous cell carcinoma indicated very early tumour relapse, these results are of minor clinical utilit y due to the absence of curative therapy. Serial measurement of CYFRA 21-1 during chemotherapy in patients with inoperable squamous cell car cinoma has shown that there is a concordance of 74% between the course of the marker and the clinical response evaluation according to the c riteria of the WHO. In a more recent study including all histological forms of lung cancer, it was found that only 59% of response evaluatio ns yielded concordant results. More data, however, are needed to suppo rt this intended clinical use.