Role of Biomarkers in Management of Prostate Cancer

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

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

3. 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

4. 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.

5. 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.

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

7. 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

8. 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.

9. 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

10. 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.

11. Purpose of PSA screening To identify those with high cancer risk who should undergo diagnostic biopsy.

12. PSA Screening approaches

13. 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

14. 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

15. 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.

16. 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.

17. 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.

18. Thank You