role of biomarkers in management of prostate cancer dr. angela amayo specialist pathologist 13 th...
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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 specificity1. 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