What is the appropriate use of tumor markers, such as Carcinoembryonic Antigen (CEA), Prostate-Specific Antigen (PSA), and Cancer Antigen 125 (CA-125), in clinical practice?

Appropriate Use of Tumor Markers in Clinical Practice

Tumor markers should not be used for cancer screening or initial diagnosis due to insufficient sensitivity and specificity, but have specific roles in monitoring treatment response and disease recurrence in patients with established cancer diagnoses. 1, 2

General Principles of Tumor Marker Use

• Tumor markers are proteins, antigens, or genes that may be elevated in cancer but lack the sensitivity and specificity to be used alone for diagnosis
• No ideal tumor marker exists - all have limitations in sensitivity, specificity, and clinical utility 3
• Clinical applications fall into four categories:
  • Screening and early detection (limited utility)
  • Diagnostic confirmation (adjunctive only)
  • Prognosis and prediction of therapeutic response
  • Monitoring disease and detecting recurrence (most established use)

Specific Tumor Markers and Their Appropriate Use

Carcinoembryonic Antigen (CEA)

• Recommended uses:

  • Monitoring response to treatment in metastatic colorectal cancer 2
  • Detecting recurrence after primary colorectal cancer treatment
  • Can be used to suggest treatment failure in metastatic breast cancer when measurable disease is absent 2

• Not recommended for:

  • Screening or initial diagnosis of colorectal or breast cancer
  • Routine surveillance of breast cancer patients after primary therapy 2

CA 15-3 and CA 27.29 (Breast Cancer)

• Recommended uses:

  • Monitoring response to treatment in metastatic breast cancer 2, 1
  • May detect recurrence with lead time of approximately 5.3 months before clinical symptoms 1
  • Two consecutive rising values are more concerning than a single elevated value 1

• Not recommended for:

  • Screening or initial diagnosis due to limited sensitivity 1
  • Routine surveillance after primary treatment 2

Prostate-Specific Antigen (PSA)

• Recommended uses:

  • Monitoring response to treatment in prostate cancer
  • Detecting recurrence after primary treatment

• Controversial use:

  • Screening for prostate cancer (value in reducing mortality remains unclear) 4

Cancer Antigen 125 (CA-125)

• Recommended uses:

  • Monitoring therapy in patients with ovarian cancer 4
  • Following treatment response in advanced ovarian cancer

• Not recommended for:

  • Population screening due to limited sensitivity for early disease

Interpretation Guidelines

• Serial measurements are more valuable than single determinations 1, 3
• Measurements should be performed in the same laboratory using the same technique 1
• Changes in levels (≥20% increase) rather than absolute values may be more meaningful 1
• Rising trend may detect recurrence before clinical or radiological evidence ("biochemical recurrence") 3
• Sampling should ideally be repeated after 5-6 half-lives of the marker 3

Management of Elevated Tumor Marker Levels

• For patients with history of cancer and elevated markers but negative workup:

  • Regular clinical examinations
  • Repeat marker testing every 2-3 months
  • Consider imaging based on clinical findings and marker trends 1

• For patients without history of cancer but elevated markers:

  • Comprehensive cancer screening
  • Evaluation for non-malignant conditions that can elevate markers
  • Repeat testing in 3-6 months if initial workup is negative 1

Common Pitfalls to Avoid

• Establishing a diagnosis based on tumor markers alone 3
• Using markers for screening in general population (high false positive rates) 5
• Ordering multiple tumor markers without clear clinical indication 5
• Failing to recognize that normal levels do not completely exclude disease 1
• Overreacting to a single elevated value rather than confirming with repeat testing

Evidence-Based Markers with Established Clinical Utility

• Estrogen and progesterone receptors for predicting response to hormone therapy in breast cancer 2
• HER-2/neu for identifying breast cancer patients likely to respond to trastuzumab 2
• KRAS mutational status for identifying colorectal cancer patients likely to benefit from anti-EGFR antibodies 4

By following these evidence-based guidelines for tumor marker use, clinicians can maximize their clinical utility while avoiding unnecessary testing and potential harm from false positive or negative results.