Lung cancer has become a major killer threatening the health of our nation, and in 2008, the Ministry of Health announced the results of the third national survey on the causes of death of residents, which showed that malignant tumors were the leading cause of death among urban residents. Among them, lung cancer has replaced liver cancer as the first cause of death of malignant tumors in China (accounting for 22.7% of all malignant tumor deaths). Over the past 30 years, the mortality rate of lung cancer in China has increased by 465%, and the incidence of lung cancer is becoming younger. The diagnosis and treatment of lung cancer deserve adequate attention from the medical community. Lung cancer can be pathologically characterized as non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC), of which NSCLC accounts for about 75%. Different pathologic typing has an important impact on the choice of treatment options. For NSCLC that cannot be surgically resected or has a high tumor load, the standard treatment option commonly used today is a combination therapy based on platinum-containing regimens. In addition to accurate diagnosis, how to assess and monitor the efficacy of cancer treatment is critical to the quality and outcome of patient care, as well as a major topic of medical research. Analysis of imaging data is a routine means of assessing tumor efficacy. However, imaging is not measurable for some lesions such as pulmonary atelectasis, pericardial effusion, pleural effusion, tumors in the former radiotherapy treatment field, lymphovascular invasive lesions, pleural lung cancer, etc. The use of tumor markers, however, can effectively fill the gap in imaging and solve this challenge. Tumor markers CEA, CYFRA 21-1 and NSE Among the common tumor markers in lung cancer, the main ones that have greater clinical significance in the assessment of efficacy and prognosis are CEA (carcinoembryonic antigen), CYFRA 21-1 (cytokeratin fragment 19), and NSE (neuron-specific enolase). CEA is a glycoprotein and is a broad-spectrum tumor marker. CEA levels are less frequently elevated in adult healthy individuals. In contrast, adenocarcinoma and large cell lung cancer cause significant elevation of CEA, which makes CEA clinically relevant in differential diagnosis of NSCLC (in combination with CYFRA 21-1), prognostic assessment, monitoring of the efficacy of treatment for advanced lung cancer, and early detection of lung adenocarcinoma recurrence. CYFRA 21-1 fragment is a cellular structural protein, which is often released into the blood in cancer patients, especially NSCLC patients’ cases, and it is the most sensitive tumor marker for NSCLC, especially for lung squamous carcinoma, and it has significant clinical value for the prognosis and efficacy assessment of NSCLC. Relevant studies have shown that the elevation of CYFRA precedes the appearance of clinical symptoms and imaging findings such as CT, which can indicate disease progression at an early stage. Before the initial treatment, the level of CYFRA can predict the efficacy of subsequent treatment. NSE is an important marker for the diagnosis of small-cell lung cancer, and high levels of NSE (>100 mg/L), when malignancy is suspected, suggests that SCLC may be present, and is also used in the differential diagnosis of ectopic neuroendocrine tumors, hepatocellular carcinoma, lymphomas, and seminomas.NSE levels are important in responding to the efficacy of treatment for SCLC, in the detection of SCLC treatment and early detection of recurrence, and in the prognostic evaluation of NSCLC. NSE is clinically important for the detection of SCLC treatment and early detection of recurrence, as well as for the prognosis of NSCLC.The diagnostic positivity rate of NSE for SCLC is 66.7%, and up to 80% in the extensive stage. Clinical assessment of CEA, CYFRA21-1 and NSE in a Chinese population with advanced NSCLC Tumor markers in lung cancer can be used for differential diagnosis and histological typing of tumors, especially for lung cancer with an unknown primary site.Significantly elevated levels of CEA, CYFRA21-1, and NSE are suggestive of malignancy, and expression and release of these tumor markers at the time of initial diagnosis is an important indicator of prognostic and therapeutic monitoring in lung cancer. CEA, CYFRA21-1 and NSE, as independent prognostic factors, are of great clinical significance for NSCLC. Whether CEA, CYFRA21-1 and NSE are suitable for chemotherapy detection and prognosis in Chinese advanced NSCLC population is an important issue for China’s oncology medical practitioners.Between October 2006 and March 2008, the Chest Hospital affiliated to Shanghai Jiaotong University conducted a clinical study on 111 patients with advanced NSCLC. The patients enrolled in this study were histopathologically or cytopathologically confirmed primary NSCLC patients with imaging stages IIIB and IV, all of whom had at least one measurable tumor lesion, had an expected survival time of more than three months, had no major organ dysfunction, and had normal bone marrow picture and liver and kidney functions. For the enrolled patients, this study used a three-generation platinum-containing chemotherapy regimen for at least four cycles of treatment. All samples were cryopreserved at -77 °C, and specimens were tested using commercial CEA, CYFRA21-1 and NSE kits. Samples were collected before the first chemotherapy and after the second chemotherapy cycle. The Kaplan-Meier method was selected to calculate the survival rate, Log-rank analysis was used to count the difference in survival rate, ox’s model was used to analyze the independent prognostic multifactorial analysis, and SPSS11.5 software was used to perform statistical calculation of the data and the effectiveness was assessed by using the RECIST criteria at every two treatment cycles.TTP (time to disease progression) and OS (overall survival time) were counted from the time of chemotherapy initiation. It was found that the time to TTP was significantly longer in the treatment-effective group, with a median value of 9.7 months in the PR (partial remission) control group, while the corresponding value in the progression (PD) group was only 2.1 months. A significant correlation between efficacy and TTP was shown. The median TTP values for patients with reduced versus elevated or maintained tumor marker CEA were 9.2 versus 4.3 months, respectively; for patients with reduced versus elevated or maintained CYFRA21-1, 9.1 versus 4.2 months; and for patients with reduced versus elevated or maintained NSE, 8.7 versus 4.7 months. It can be seen that effective radiotherapy and CYERA reduction were predictors of TTP. In addition the CEA lowering group and NSE lowering group also showed a treatment effect of prolonged TTP. Notably, patients with decreased levels of all 3 markers had the longest TTP. In terms of OS, the one-year survival rate of the 111 patients selected for the study was 69.4%, with a median OS value of 19.2 months. Similar to the case of TTP, OS was likewise significantly prolonged in the treatment-effective group. Whereas both tumor markers showed a correspondence between decreased index and significantly prolonged OS, except for NSE, which had no corresponding response, OS was significantly prolonged in both the CEA and CYFRA baseline normal groups.The median value of OS for patients with reduced versus elevated or maintained CEA was 30.1 months versus 14.1 months, respectively. This suggests that CEA reduction, CEA baseline and CYFRA21-1 are all valid predictors of OS. Taken together, several data proved that the levels of CEA, CYFRA and NSE before and after treatment were correlated with the efficacy of treatment, in which the change of CYFRA 21-1 level after chemotherapy was an independent prognostic factor for TTP, while the change of CEA level after chemotherapy was an independent prognostic factor for OS. Guideline recommendations for the application of tumor markers in lung cancer As independent prognostic factors recommended by the major international academic organizations of tumor markers, EGTM (European Group for Tumor Markers) and NACB (National Academy of Clinical Biochemistry), CEA, CYFRA21-1, and NSE are recommended to be applied in the diagnosis, treatment, evaluation, and monitoring of NSCLC. International academic organizations tend to select appropriate markers based on histological type. (e.g., Table I) Relevant application guidelines show that the speed and degree of tumor marker decline is a predictor of patient regression in postoperative follow-up. The decline in tumor markers is related to the half-life of the tumor marker and the residual tissue of the tumor. Exclude renal/hepatic insufficiency if slow clearance or elevation of tumor markers suggests residual tumor lesions or disease recurrence. In systemic therapy, CYFRA 21-1 was the marker with the best concordance with NSCLC treatment efficacy, and CYFRA had a specificity of 100% and a sensitivity of 52% in monitoring disease progression. Moreover, tumor markers are sensitive markers of cancer recurrence, often suggesting disease progression months in advance of imaging changes. CYFRA 21-1 is a very good prognostic marker for NSCLC, with a sensitivity of 79% for NSCLC, and up to 100% for patients with preoperative levels above 3.3 μg/L. Changes in tumor markers can be made 2-15 months earlier than imaging and clinical diagnosis. Discussion In conclusion, tumor markers such as CEA, CYERA and NSE are of great value in the treatment of lung cancer, which can not only assist clinicians in evaluating the efficacy of treatment, selecting subsequent treatment plans and assessing the prognosis, but are also of great significance for tumors that cannot be evaluated by imaging. Among them, CYFRA 21-1 can be used as an independent prognostic marker for TTP, and CEA can be used as an independent prognostic marker for OS. However, the use of tumor markers for the follow-up of asymptomatic population after initial treatment is still controversial, but the selection of appropriate markers for continuous monitoring provides an early clinical basis for tumor surgical outcome and recurrence. In systemically treated NSCLC, CEA and CYFRA 21-1 monitoring may reflect the efficacy of treatment and early detection of tumor progression. Reliable criteria for tumor marker progression remain to be validated by future clinical studies investigating tumor marker interventions. In continuous dynamic monitoring, the same tumor marker test reagents and methods should be used, and test reports and patient medical record documentation should indicate the above information.