BACKGROUND: This study applied a combined cancer biomarker panel to clinically identify small cell lung cancer (SCLC) and nonsmall cell lung cancer (NSCLC) in a high-risk population. METHODS: The serum levels of 4 biomarkers (progastrin-releasing peptide [ProGRP], carcinoembryonic antigen [CEA], squamous cell carcinoma antigen [SCC], and cytokeratin 19 fragment [CYFRA21-1]) were determined in 153 patients with a high risk of lung cancer (12 with a new diagnosis of SCLC, 52 with NSCLC, and 89 without lung cancer). Information about diagnosis delays was collected through interviews of all participants. RESULTS: Significantly higher serum levels of ProGRP (P <.0001) were found among the SCLC patients versus the rest of the population. A receiver operating characteristic curve analysis established the cutoff values of ProGRP, CEA, SCC, and CYFRA21-1 as 300 pg/mL, 7.3 ng/mL, 3 ng/mL, and 6.5 ng/mL, respectively. The sensitivity and specificity of ProGRP in diagnosing SCLC were 75% and 100%, respectively. Among the 14 lung cancer patients with a false-negative computed tomography (CT) result, the diagnostic panel detected 8 additional cancers. CONCLUSIONS: This panel increased the diagnostic specificity for high-risk subjects (those with renal failure being excluded), and auxiliary to a CT scan, it increased the sensitivity for patients with lung cancer. These results might be applied to shorten the diagnosis delay at health care institutions in China. Cancer 2015;121:3113-21. V C 2015 American Cancer Society.KEYWORDS: biomarker, delayed diagnosis, non-small cell lung cancer, progastrin-releasing peptide (ProGRP), small cell lung cancer.
INTRODUCTIONCurrently, lung cancer is the most common cancer and the leading cause of cancer-related deaths worldwide. 1 Lung cancer has replaced liver cancer to become the top killer among malignant tumors in China for the past 3 decades, during which the registered mortality rate for lung cancer increased by 465%. 2,3 Among lung cancer deaths, 87% are attributable to cigarette smoking. 4 The mortality rate of lung cancer is approximately 23 times higher for current male smokers and 13 times higher for female smokers versus lifelong nonsmokers. 5 A population-based, cross-sectional study estimated the total number of lung cancer deaths in China to be 493,348 (338,346 males and 155,002 females) in 2008. 6 The variations in lung cancer mortality rates between males and females seen in China and across other countries reflect differences in the stages and degrees of the tobacco epidemic. [7][8][9][10]