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