What are cancer markers and how are they used in cancer screening and diagnosis?

Cancer Markers: Role in Screening and Diagnosis

Cancer markers are substances produced by cancer cells or in response to cancer that can be detected in blood, urine, or tissue samples and are used for diagnosis, monitoring treatment response, and predicting outcomes in cancer patients. 1, 2

Types of Cancer Markers

• Serum-based markers are the most commonly used due to their relative ease of testing and lower cost compared to tissue-based or radiology-based markers 1
• Tissue-based markers require biopsy specimens and are often used for diagnosis and treatment planning 2
• Molecular markers include genetic mutations, gene expression patterns, and other molecular changes that can be detected through various laboratory techniques 3

Common Cancer Markers and Their Clinical Applications

Diagnostic Markers

• Alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (β-hCG) are used in males with suspected germ cell tumors 4
• Prostate-specific antigen (PSA) is used in males with possible prostate cancer, though its value in screening remains controversial 4, 3
• Carcinoembryonic antigen (CEA) is primarily used for monitoring colorectal cancer rather than diagnosis 4
• Cancer antigen 125 (CA125) is used in females with suspected gynecological malignancies 4, 3
• Chromogranin A is used in patients with possible neuroendocrine malignancies 4

Prognostic Markers

• Lactate dehydrogenase (LDH) correlates with tumor burden and has established prognostic significance across multiple tumor types 5
• Elevated CEA levels (≥5 mg/mL) may correlate with poorer prognosis in colorectal cancer patients 4
• Oncotype DX assay can predict recurrence risk in node-negative, estrogen-receptor positive breast cancer patients treated with tamoxifen 4

Monitoring Treatment Response

• CEA is the marker of choice for monitoring metastatic colorectal cancer during systemic therapy and should be measured at the start of treatment and every 1-3 months during active treatment 4
• CA125 is used for monitoring therapy in patients with ovarian cancer 3
• Despite non-tumor type-specific elevations of markers like CEA, CA19-9, CA15-3, and CA125, these can be used to determine disease course and monitor treatment response 4

Limitations of Cancer Markers in Screening

• Serum cancer markers have poor mass screening utility due to low positive predictive value 1
• Non-cancerous conditions can cause elevation of some tumor markers above normal levels 2
• Not every cancer patient will have elevated levels of a tumor marker 2
• The American Society of Clinical Oncology does not recommend using circulating tumor cell (CTC) measurements to make breast cancer diagnoses or influence treatment decisions 4

Guidelines for Cancer Marker Use in Clinical Practice

• Postoperative serum CEA testing should be performed every 3 months in patients with stage II or III colorectal disease for at least 3 years after diagnosis 4
• Persistently rising CEA values above baseline should prompt restaging but may suggest progressive disease even without corroborating radiographic evidence 4
• Caution should be used when interpreting rising CEA levels during the first 4-6 weeks of new therapy, as spurious early rises may occur, especially after oxaliplatin treatment 4
• Multiple measurements of markers over time provide more valuable prognostic information than single determinations 5, 6

Emerging Approaches in Cancer Marker Research

• Gene expression profiling can be used to discover genes that may predict responsiveness to specific drugs in cancer cell lines 4
• Polymorphisms in genes like TS, DPD, UGT1A1, and CYP3A4 are being studied as potential predictors of response to specific cancer drugs 4
• Multiparameter gene expression analysis, such as Oncotype DX, has emerged as a valuable tool for predicting recurrence risk and guiding treatment decisions in breast cancer 4
• Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) guidelines have been developed to improve the quality and transparency of tumor marker research 4

Clinical Application Considerations

• Cancer markers should be interpreted in conjunction with clinical findings, imaging studies, and when necessary, biopsy results 4, 6
• The specific tumor type, stage, and treatment history must be considered when evaluating prognostic markers 5
• Adherence to standardized reporting guidelines (REMARK) is essential for improving the quality and comparability of tumor marker studies 4
• Acquisition of DNA samples with appropriate consent for future use should be included in major cancer trials to advance pharmacogenomic research 4