What is the role of tumour (tumor) markers, such as carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125), and prostate-specific antigen (PSA), in monitoring disease progression and response to treatment in patients with a history of cancer?

Role of Tumor Markers in Monitoring Cancer Patients

Tumor markers should NOT be used for screening, diagnosis, or routine surveillance after primary therapy, but can be valuable adjuncts—never standalone tests—for monitoring metastatic disease during active treatment when combined with imaging and clinical examination. 1, 2

Context-Specific Applications

Breast Cancer Monitoring

For metastatic breast cancer during active therapy:

• CA 15-3 or CA 27.29 are the primary markers (elevated in 75-90% of metastatic cases), used alongside imaging and physical examination—never alone 1, 2
• Rising CA 15-3/CA 27.29 indicates treatment failure when readily measurable disease is absent, but requires imaging confirmation before changing therapy 1, 3
• CEA has limited complementary value (elevated in only 50-60% of metastatic cases) and adds minimal sensitivity (2.1%) when CA 15-3 is already elevated 1, 2
• Measure CEA only if CA 15-3/CA 27.29 is not elevated, as it may provide supplementary information in select cases 1, 2

Critical timing consideration:

• Do NOT interpret rising markers during the first 4-6 weeks of new therapy due to spurious early elevations that do not reflect true progression 1, 3

Colorectal Cancer Monitoring

CEA for metastatic colorectal cancer:

• CEA can be measured every 1-3 months during active treatment for locally advanced or metastatic disease 1
• Rising CEA suggests progressive disease but requires confirmation with imaging or biopsy before treatment modification 1
• CEA cannot provide definitive evidence of recurrence alone and must be corroborated with other studies 1

Pancreatic Cancer Monitoring

CA 19-9 for pancreatic cancer:

• CA 19-9 can be measured at treatment initiation and every 1-3 months during active therapy for locally advanced or metastatic disease 1
• Elevated serial CA 19-9 may indicate progressive disease but requires confirmation with imaging or clinical findings 1
• CA 19-9 alone cannot determine operability or provide definitive evidence of recurrence 1

Ovarian Cancer Monitoring

CA-125 for ovarian cancer:

• CA-125 is useful for monitoring therapy response in patients with diagnosed ovarian cancer 4, 5
• CA-125 measured relative to CEA helps distinguish ovarian from gastrointestinal primaries when evaluating peritoneal carcinomatosis of uncertain origin 6

What NOT to Do: Common Pitfalls

Explicitly contraindicated uses:

• Never use tumor markers for cancer screening in asymptomatic populations due to low sensitivity and specificity 1, 2
• Never use markers for initial cancer diagnosis as they lack adequate sensitivity for early-stage disease 1, 2
• Never use markers for routine post-surgical surveillance after curative treatment, as early detection of recurrence does not improve survival or quality of life 1, 2
• Never rely on markers alone without concurrent imaging and clinical assessment 1, 2

The most common error: Ordering CEA or CA 15-3 for routine follow-up after breast cancer surgery, which leads to overdiagnosis without survival benefit 2

Prognostic Value (Limited Clinical Impact)

• Pre-treatment CA 15-3 levels correlate with disease stage but are not independent prognostic factors 1
• Initial CA 15-3 >50 kU/L warrants metastatic workup before finalizing treatment plans 1
• Persistently elevated markers despite treatment indicate poor prognosis and treatment failure 1

Practical Algorithm for Marker Use

Step 1: Confirm metastatic disease with imaging/biopsy first

Step 2: Establish baseline marker levels at treatment initiation:

• Breast cancer: CA 15-3 or CA 27.29 (if not elevated, add CEA) 1, 2
• Colorectal cancer: CEA 1
• Pancreatic cancer: CA 19-9 1
• Ovarian cancer: CA-125 4

Step 3: Monitor every 1-3 months during active therapy 1

Step 4: Interpret trends, not single values:

• ≥20% increase suggests progression 3
• Ignore changes in first 4-6 weeks of new therapy 1

Step 5: Confirm rising markers with imaging before changing treatment 1, 2

Evidence Quality Note

The American Society of Clinical Oncology guidelines 1 represent the highest quality evidence for breast cancer markers, while the 2006 ASCO gastrointestinal guidelines 1 provide definitive recommendations for CEA and CA 19-9. Critically, no prospective randomized trials demonstrate that marker-based early detection of recurrence improves survival, disease-free survival, or quality of life 1, which is why routine surveillance use is explicitly discouraged despite markers' ability to detect recurrence 5-6 months earlier than clinical symptoms 1.