Tumour markers

1. Introduction
2. Definition
3. Classification
4. Technique
5. Ideal tumour marker
6. Uses in urology
7. Tumour marker used in Urology
8. Tumor markers
1) Prostate
a. PSA
b. PAP
c. PCA3
2) Bladder
a. BTA stat
b. BTA TRAK
c. NMP 22
d. Telomerase
e. UroVysion
3) Testis
a. AFP
b. hCG
c. LDH
d. PLAP
4) Adrenal
a. Cortisol
b. Aldosterone
c. Androgen & Oestrogen
5) Kidney
a. VEGF
b. Erythropoietin
c. HIF-1
d. CD 44
6) UTUC
a. Epithelial Cadherin
8. Conclusion
 2

Introduction
In the recent years, knowledge about tumour marker has increased tremendously providing
great opportunities for management of cancer patients. A comprehensive understanding of the
relevance of each tumour marker is very important for diagnosis and helpful for the choice of
multiple treatments.

Definition
A tumour marker is a biomarker found in blood, urine and body tissues and it can be
elevated by the presence of one or more type of cancer.

Classification
Tumour marker can be protein, peptide, carbohydrate or gene.
1. Hormone – hCG
2. Enzyme – PSA
3. Cancer Ag – Ca 19.9
4. Oncofetal Ag – AFP

Techniques
Tumour marker can be assessed by immunoassay or enzyme activity determination.

Ideal tumour marker

Ideal tumour marker should have the following properties. In reality, ideal tumour marker
does not exist.
1. Present in blood
2. Undetectable in health
3. produced only by malignant cells
4. Highly sensitive
5. Highly specific
6. Concentration propotion to tumour mass

Uses in Urology
1. Screening
2. Prediction of risk
3. Approach to Diagnosis
4. Prediction of staging (PSA with T stage of DRE and Gleason score)
5. Prognosis
6. Monitoring of therapy
7. Monitoring of recurrence

Tumour marker used in Urology

1. Prostate – PSA
2. Bladder – BTA, NMP 22, ImmunoCyst, UroVysion
3. UTUC – Epithelial cadherin
4. Testis – AFP, hCG, LDH, PLAP
5. Adrenal – Cortisol, Aldosterone, Androgen & Oestrogen
6. Renal – VEGF, Erythropoietin, HIF-1
 3

Prostate Cancer
Introduction
PSA is very useful tumour marker for PC. Prior to PSA era, most men with newly diagnosed
PC had advanced incurable disease. It is hK3 protein located on chromosome 19. It is serine protease
and liquefies the ejaculate for fertilization. It is produced by columnar cells of ducts and acini of
prostate. It is mostly found in serum and small amount found in blood and urine. 75% of serum PSA
is complexed and 25% is free. Half life is 2.2 days. Normal range is <4 ng/ml. It is androgen
dependent and varies with race, age, BMI and prostate volume.
PSA is organ specific and not cancer specific. So, it is elevated not only in PC but also in BPH,
prostatitis, UTI, recent ejaculation, prostate injury, vigorous cycling and instrumentation. It may be
low or mask of high level in obesity and use of 5ARI, aspirin and statin.

Indications for checking PSA

1. Patient request
2. LUTS
3. Abnormal DRE
4. Progressive bone pain (Back pain)
5. Unexplained anaemia, anorexia or weight loss
6. Spontaneous thromboembolism or unilateral leg swelling
7. Monitoring of PC

Counselling before PSA test

Counselling is the mandatory before offering PSA to asymptomatic men especially iin
screening. It is less fundamental for symptomatic patient but all patient should be informed.
The following points should be used.
1) Cancer will be identified in <5% of men screened.
2) The benefit of PC screening is controversial.
3) Sensitivity is 80%.
4) Specificity is 40-50% (Other causes of increased PSA must be explained).
5) Prostate MRI can cause distress & claustrophobia.
6) Prostate biopsy is uncomfortable & may miss cancer.
7) Treatment may not be necessary, curative and treatment related morbidity could lead to
a diminished QoL.

Types of PSA test (Total PSA & PSA derivatives)

1. Total PSA
It generally increases with advancing stage and tumour volume. But small propotion of
poorly differentiated tumour fails to express PSA.
1. Any PSA rise from its nadir when on 5ARI treatment for BPH should be considered
for biopsy.
2. If PSA of <1.0 ng/ml at age 60, 0.2% risk of PC death is present.
3. If PSA >10 ng/ml, >50% of patients have extraprostatic disease.
4. If PSA <20 ng/ml, <5% of patients have obturator lymph node metastasis and 1%
have bone metastasis.
5. If PSA >50 ng/ml, 66% of patients have lymphatic involvement, 90% have seminal
vesicle involvement.
PSA should be undetectable (<0.01 ng/ml) following RP for gland confined disease. PSA
rise after RP precedes the development of metastasis disease by a mean time of 8 years. In
80% of patients with metastasis, PSA fall to within normal limit after 4 months of ADT.
PSA also used in some criminal cases of rape.
 4

2. F:T PSA
It increases the specificity of total PSA because the ratio is lower in PC than BPH. So, it is
helpful in deciding to re-image or re-biopsy in previous benign biopsy. Total PSA (4-10 ng/ml)
and normal DRE have 25% risk of PC. This risk rise to 60% if F:T ratio is 10%. This risk fall to
10% if F:T ratio is 25%. Normal value = >20%
3. PSAV
PSAV is defined as the rise in PSA per year in ng/ml. Velocity of >0.75 ng/mL is associated
with an increased risk of PC. Ideally at least 3 PSA are required.
PSAV = 0.5 x (PSA2 – PSA1/ time 1 in year + PSA3 – PSA2/ time 2 in year)
Normal value = <0.6 -0.75 ng/ml/year

4. PSADT
It is defined as the length of time that a patient's PSA takes to double in months or years.
It is useful in patient under survillance for high PSA and negative biopsy.
Normal value = > 3 Years

5. PSAD & PSATZD

It is defined as the serum PSA per ml of prostate tissues. Increased PSAD is likely to lead
to the diagnosis of PC.
Normal value = 0.15 ng/ml/ml of prostate tisssues
Prostate volume = Height x Width x Length x 0.52

6. sPSA
Undetectable PSA is defined as <0.01 ng/ml. sPSA enables PSA to be detected to a
threshold of 0.003 ng/ml. It is used for early detection of biochemical relapse after RP.

uPM3/ PCA3
uPM3 test detects prostate cancer antigen 3. It is performed by collecting the first 20-30 ml
of urine voided following vigorous prostatic messsage. It is used in persistently elevated PSA with
negative biopsy for further biopsy.

Biochemical recurrence (BCR)/ PSA relapse

BCR is defined as rise in PSA to 0.2 ng/mL and a confirmatory value of >0.2 ng/mL following
RP or a rise of >2ng/mL above the Nadir after RT.
 5

Bladder Cancer
Cystoscopy remain the gold standard for Ca bladder detection and urine cytology is the most
accurate and non invasive test for Ca bladder. But, several novel urinary markers have been
developed. These are high sensitivity but lower specificity. Currently, these markers are not
accepted for diagnosis or follow up in clinical practice.
1. NMP 22
2. BTA stat
3. BTA TRAK
4. UroVysion (FISH)
5. Telomerase

Testicular Cancer
Across the board for all testicular cancer, 51% will have elevated tumor markers. Commonly
used tumour markers are AFP (Half life 5-7 Days), hCG (Half life 24-36 Hours) and LDH (24 Hours).
They are both diagnostic and prognostic. Measurement after orchidectomy and their half life
decline are useful in assessment for retroperitoneal and metastastic disease.
1. Seminoma – hCG
2. NSGCT – hCG & AFP/ LDH (Tumour burden)
(Choriocarcinoma do not secrete AFP)

Adrenal Tumour
Functioning adrenal tumour can be assessed with tumour markers.
Medulla arising tumour (Pheochromocytoma)
1. Blood (Catecholamines-fractionated/ Epinephrine/ Norepinephrine/ Dopamine)
2. 24 Hr urine collection (Catecholamines-total/ Metanephrine/ Normetanephrine/
Dopamine)
Cortex arising tumour
1. Cushing's Syndrome (Cortisol)
2. Conn's Syndrome (K+/ PRA/ PAC)
3. Adrenal Cancer (DHEA/ Testosterone)

Renal cell carcinoma

There is no established tumor marker for RCC. The followings may be investigated, but still in
trial.
1. Screening (ESR, Fibrinogen)
2. Staging (ESR, Fibrinogen, CEA, Erythropoietin)
3. Prognosis (ESR, CEA, CRP, VEGF, Erythropoietin, Ferritin)

Conclusion
A comprehensive understanding of the relevance of tumor marker (liquid biopsy) will be
very important to efficiently diagnose the disease and provide appropriate direction to definitive
management to benefit the unfortunate patients.

Dr Aung Ko Htet