Role of Biomarkers in Management of Prostate Cancer

Role of Biomarkers in Management of Prostate Cancer Dr. Angela Amayo Specialist Pathologist 13th April 2012

Outline Review • Performance characteristics of PSA markers • Limitations of PSA • Guidelines for clinical utility of PSA in screening and treatment monitoring.

Tumour Biomarkers • Substances usually found in body fluids. • Used to determine the presence of tumours. • Are produced by - tumour cells, or - host cells in response to presence of tumour

Prostate Specific Antigen (PSA) • A protease enzyme produced by prostatic epithelial cells. • Circulates in blood in free form or bound to α1- antichymotrypsin. • Serum reference values < 2ug/L • Elevations found in prostatitis, BPH and Prostate cancer. • PSA use reported to contribute greatly to early Ca prostate diagnosis.

Criteria for assessing usefulness of tumour biomarkers:• High sensitivity – detectable when only few cancer cells present. Sensitivity = TPos TPos+ FNeg • High specificity – not detectable in healthy individuals or in non-malignant disease. Specificity = TNeg TNeg + FPos.

Clinical Utility of PSA • Screening – Widespread use • Diagnosis – Limited use • Prognosis – Limited usefulness. • Treatment Monitoring - Indicated

PSA Performance characteristics in screening At cut-off of 4 ug/L: - Sensitivity 78% - Specificity 33%.

Causes of low specificity: • Elevations in non malignant situations BPH Prostatitis Prostate surgical procedures

Approaches to increase PSA specificity 1. Use of free PSA • For PSA 4-10ug/L • Estimate percent free PSA. • Low % free PSA associated with higher likelihood of cancer. % Free PSA

Cancer Risk

> 25%

4, increase >0.75ug/L/yr significant • In PSA 0.5ug/L/yr significant.

Purpose of PSA screening

To identify those with high cancer risk who should undergo diagnostic biopsy.

PSA Screening approaches Authority

Recommendations

American Cancer Society

Annual Screening From 50 – 76 years Afr Ame from 45 years

American College of Physicians

Above with proviso – inform clients of risks and benefits. Clients make informed choice.

Kenya

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Use of PSA in treatment monitoring 1. Assessment of completeness of surgery • Following prostatectomy, PSA levels should be < 2ug/L. • PSA should be measured after 6 weeks (allow clearance of PSA released during surgery). • Persistent elevations may suggest residual tumour or metastatic disease

Use of PSA in treatment monitoring 2. Active surveillance or follow up after surgery/ radiation • Important use of tumour biomarker • Evaluates success of therapy • Aid in early detection of recurrence

Biomarkers in treatment monitoring • Decrease in marker level to normal indicates effective treatment. • Persistent elevation of marker indicates residual disease or metastases. • Renewed increase after period of normal indicates recurrence of tumour. • Requires serial estimations of biomarkers. • Method used for testing important for interpretation of serial results. • Same analytical method should be used.

Interpretation of biomarker during treatment monitoring • No change- Marker does not fall to