Background The standard for clinical staging of lung cancer is the use of CT and PET scans, however, these may underestimate the burden of the disease. The use of serum tumor markers might aid in the detection of subclinical advanced disease. The aim of this study is to review the predictive value of tumor markers in patients with clinical stage I NSCLC. Methods A comprehensive search was performed using the Medline, EMBASE, Scopus data bases. Abstracts included based on the following inclusion criteria: 1) adult ≥18 years old, 2) clinical stage I NSCLC, 3) Tumor markers (CEA, SCC, CYFRA 21-1), 4) further imaging or procedure, 5) > 5 patients, 6) articles in English language. The primary outcome of interest was utility of tumour markers for predicting nodal involvement and oncologic outcomes in patients with clinical stage I NSCLC. Secondary outcomes included sub-type of lung cancer, procedure performed, and follow-up duration. Results Two hundred seventy articles were screened, 86 studies received full-text assessment for eligibility. Of those, 12 studies were included. Total of 4666 patients were involved. All studies had used CEA, while less than 50% used CYFRA 21-1 or SCC. The most common tumor sub-type was adenocarcinoma, and the most frequently performed procedure was lobectomy. Meta-analysis revealed that higher CEA level is associated with higher rates of lymph node involvement and higher mortality. Conclusion There is significant correlation between the CEA level and both nodal involvement and survival. Higher serum CEA is associated with advanced stage, and poor prognosis. Measuring preoperative CEA in patient with early stage NSCLC might help to identify patients with more advanced disease which is not detected by CT scans, and potentially identify candidates for invasive mediastinal lymph node staging, helping to select the most effective therapy for patients with potentially subclinical nodal disease. Further prospective studies are needed to standardize the use of CEA as an adjunct for NSCLC staging.

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Metastasectomy by an open approach, which affords bimanual palpation of the entire lung, discovered ipsilateral non-imaged malignant pulmonary metastases in 36% of cases (41% of mesenchymal tumors).