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% <10% < 10% 56% Approaches to increase PSA specificity 2. Use of age dependent reference values. • Improves detection of cancer in younger adults. Age Reference values 40 – 49 yrs 0 – 2.5 ug/L 50 – 59 yrs 0 – 3.5ug/L 60 – 69 yrs 0 – 4.5ug/L Approaches to increase PSA specificity 3. Use of PSA dynamics • Includes PSA velocity and PSA doubling time. Based on annual PSA testing. • Measures rate of PSA increase over time. • Highest increase rate in cancer. • In PSA >4, increase >0.75ug/L/yr significant • In PSA <4, increase > 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 ? 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 <50% of pretreatment values. • Improvement- Marker falls to < 50% of pretreatment values. • Response – Marker falls to <10% pretreatment values. • Complete response- Marker falls to normal reference value. SUMMARY • PSA is an organ specific tumour biomarker. • Specificity of PSA for Ca Prostate is low • Knowledge of the performance characteristics is important. • Approaches can be used to improve specificity. • Useful role for PSA in treatment monitoring. • Analytical method used important for interpretation of results. Thank You