Lung cancer remains a significant global health concern, being a leading cause of cancer-related deaths worldwide. Early detection can improve survival rates, but conventional methods often involve radiation exposure or invasive procedures. Blood markers offer a less invasive way to gain insights into health, and this article explores their role in lung cancer.
Understanding Blood Markers in Cancer
Blood markers, also known as biomarkers, are substances that can be measured in blood or other bodily fluids. These substances are often proteins or genetic material, which can indicate the presence of disease, the body’s response to disease, or the effect of a specific treatment. They are detected through blood tests, making them a less invasive alternative to tissue biopsies. While some markers are specific to a single cancer type, others can be found in various cancers or even in non-cancerous conditions.
Key Blood Markers for Lung Cancer
Several blood markers are used or emerging for lung cancer, categorized as protein or genetic markers. Protein markers include:
- Carcinoembryonic Antigen (CEA), elevated in various cancers including lung adenocarcinomas.
- Cytokeratin 19 Fragment (CYFRA 21-1), useful for non-small cell lung cancer (NSCLC), especially squamous cell carcinoma.
- Neuron-Specific Enolase (NSE), more specific for small cell lung cancer (SCLC).
- Pro-gastrin-releasing peptide (ProGRP), primarily associated with SCLC.
Circulating tumor DNA (ctDNA) is a genetic marker that detects tumor fragments shed into the bloodstream. ctDNA can reveal specific genetic alterations, such as mutations in the Epidermal Growth Factor Receptor (EGFR) gene, or rearrangements in the ALK and ROS1 genes. These insights guide the selection of targeted therapies. Additionally, ctDNA testing can assess PD-L1 expression and tumor mutational burden (TMB), relevant for immunotherapy decisions.
Applications in Lung Cancer Management
Blood markers contribute to lung cancer management, complementing other diagnostic tools. Though not used for standalone diagnosis, they support diagnosis by providing additional information alongside imaging and biopsies. For instance, a panel combining markers like CYFRA21-1, CEA, and SCC-Ag has shown improved sensitivity and specificity for NSCLC diagnosis. Marker levels also offer insights into prognosis, predicting disease aggressiveness or patient outcomes. Elevated levels of CEA, CYFRA 21-1, and NSE, for example, have been associated with poorer outcomes in squamous cell carcinoma of the lung.
Blood markers also monitor treatment effectiveness; a decrease in levels may indicate treatment is working, while an increase might suggest disease progression or recurrence. Serial monitoring of ctDNA, for example, can detect resistance mutations like EGFR T790M during treatment with EGFR inhibitors. Molecular markers from ctDNA are useful for guiding targeted therapies, identifying patients who benefit from medicines targeting mutations like EGFR, ALK, or ROS1.
Considerations and Limitations
Despite their utility, blood markers in lung cancer have limitations. They are not used for standalone diagnosis because non-cancerous conditions can cause elevated levels (false positives), and cancer can be present even if levels are not elevated (false negatives). Therefore, blood marker results must always be interpreted with other diagnostic tools, such as CT scans, PET scans, and tissue biopsies.
Variability in marker levels among individuals and across different stages and types of lung cancer also presents challenges. For example, the prognostic significance of serum tumor markers can vary with histology and stage. Ongoing research aims to improve the accuracy and utility of these markers, exploring new technologies and combinations of biomarkers to enhance their diagnostic and prognostic value.