Increased CYFRA 21-1 and CEA levels are negative predictors of outcome in p-stage I NSCLC

Thomas Muley, Hendrik Dienemann, Werner Ebert
Anticancer Research 2003, 23 (5): 4085-93
Besides established factors, we assessed the prognostic impact of tumor markers CYFRA 21-1, CEA and NSE on survival probability in a series of 515 NSCLC patients who were treated by surgery. In addition, we studied the prognostic significance of CYFRA 21-1 and CEA with reference to the individual postoperative (p-) stages. It was found that p-stages correlated inversely with survival probability. Complete resection had a favourable impact on prognosis (R0 versus R1/R2: p < 0.0001). Among patient characteristics, we found that age (> 70 years) was an unfavourable prognostic factor (p = 0.0014). Performance status (PS, ECOG) also pointed to an adverse prognosis for PS 1-2 versus PS 0 (p = 0.014), whereas gender was not prognostically important. Elevated LDH levels (> 240 U/l), although non-specific, had adverse prognostic significance (p = 0.0034). Patients with CYFRA 21-1 levels above 3.3 ng/ml had a median survival of 24.2 months compared to 55.0 months for patients with marker levels below that cut-off point (p < 0.0001). CEA levels above 9.8 ng/ml were also associated with shorter survival. Median survival was 19.2 months versus 49.9 months in patients with CEA levels below 9.8 ng/ml (p < 0.0001). NSE was of no prognostic value. However, increased NSE levels (> 14.5 ng/ml) in a subgroup of patients with advanced stages IIIa up to IV were found to be associated with shortened survival (p = 0.024). In p-stage I, 3-year survival was shorter for patients with abnormal CYFRA 21-1 levels compared to patients with normal marker expression (60.2% versus 78.4%, p = 0.015). CEA was also of prognostic value in this stage (p = 0.013). In p-stage II, patients with normal CYFRA 21-1 and CEA levels tended to have a better outcome (p = 0.064 and 0.09, respectively). Combined use of both markers showed that stage I patients in whom both markers were normal had a 3-year survival rate of 82.5% compared to those where at least one marker was abnormal (3-year survival: 55.7%, p = 0.0014). It is concluded that tumor markers CYFRA 21-1 and CEA proved to be important adjuncts to the staging system and may help to better assess prognosis. A subgroup of p-stage I patients at high risk was identified by elevated marker levels. These patients may benefit from adjuvant chemotherapy.

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