Novel markers predict NSCLC prognosis

Serum levels of cytokeratin 19 fragment (CYFRA)21-1 and sialyl-Lewis x (SLex) are prognostic markers for non-small-cell lung cancer (NSCLC), and the combination of the two factors may contribute to the classification of these patients, suggest Japanese study results.

It is crucial that patients with advanced lung cancer are diagnosed accurately, as primary disease is one of the most aggressive solid tumors. However, current techniques result in 25% of patients diagnosed with N2-negative NSCLC pre-operatively subsequently being found to have metastases to mediastinal lymph nodes.

To examine the significance of pre-operative serum levels of CYFRA21-1 and SLex, Shinjiro Mizuguchi and colleagues from Osaka City University Medical School studied 272 patients with NSCLC, who were aged a median of 69 years. All of the patients underwent pulmonary resection with mediastinal lymph node dissection.

Carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC) levels were assessed alongside CYFRA21-1 and SLex levels, the team notes in the Annals of Thoracic Surgery.

Survival rates were associated, on a log-rank test, with age, gender, and performance status, along with serum CEA, SCC, CRFRA21-1, and SLex levels. Multivariate analysis revealed that age, gender, and performance status were independent prognostic factors, as were high levels of CYFRA21-1, at a risk ratio [RR] of 2.42, and SLex, at a RR of 6.18. Patients who were positive for both markers had a RR of 6.10 in comparison with those negative for both.

For patients negative for both markers, the 1-, 3-, and 5-year survival rates were 98%, 82%, and 75%, respectively. This compared with corresponding values of 90%, 63%, and 49% for those who were positive for either marker, and 62%, 31%, and 25% for those who were positive for both. Of the patients positive for both markers, 64% had histologic stage III/IV disease, whereas 68% of those negative for both had stage I disease.

"In conclusion, serum CYFRA21-1 and SLex were prognostic markers in patients with NSCLC," the team says, adding that the combination of the two should significantly contribute to the classification of NSCLC patients.

Thomas D'Amico, from Duke University Medical Center in Durham, North Carolina, wrote in an accompanying commentary: "Although prognostic information may be attained from initial serum titers of tumor markers, these markers continue to be secreted into the peripheral circulation of patients with continued and recurrent disease.

"The use of serial serum determinations enables analysis of protein expression within time, and changes in protein levels may be more important than the absolute value of the protein."



Ann Thorac Surg 2007; 83: 216–222