Testicular Tumour Markers

Testicular Tumour Markers

Introduction

• Substances detected in the blood, urine or tissues that are associated with the presence of cancer

• Produced either by the tumour, by the body in response to the cancer but also in some benign conditions

• Useful in screening, diagnosis, staging, prognosis and monitoring response to treatment

Testicular Tumour Markers

• Oncofetal proteins:
• Alpha-fetoprotein (AFP)
• Human chorionic gonadotrophin (ß-hCG)

• Cellular enzymes:
• Lactate dehydrogenase (LDH)
• Placental alkaline phosphatase (PLAP)

AFP

• Normal fetal serum protein – fetal yolk sac, liver and GI tract. Trace amounts after age 1 year.
• Expressed by trophoblastic elements in 50-70% of terotomas and yolk sac tumours.
• Raised AFP is NEVER found in pure seminoma or pure choriocarcinoma.
• In seminomas, suggests the presence of non-seminomatous element.
• Serum half-life: 5-7 days.
• [<10 ng/ml].

ß-hCG

• Glycoprotein with alpha and beta subunits.
• Produced by syncytiotrophoblastic cells of placenta.
• Expressed by syncytiotrophoblastic elements of:
• choriocarcinomas (100%).
• terotomas (40%).
• seminomas (10-15%).
• pure seminomas (0-5%).
• Serum half-life: 24-36 hours.
• [ß-subunit <5 mIU/ml, <1 ng/ml]

LDH

• Ubiquitous cellular enzyme (muscle, liver, kidney and brain).
• Marker of all germinal cell tumours (less specific than AFP or ß-hCG).
• Seminomas: Elevated in 10-20% (metastatic disease 80%).
• NSGCTs: Elevated (metastatic disease 50-60%).
• Degree of elevation correlates with tumour burden.
• Useful in monitoring treatment response in advanced seminoma.
• Prognostic value in patients with metastatic disease and is therefore included in staging.

PLAP

• Fetal isoenzyme - different from adult alkaline phosphatase.
• Advanced GCTs: Elevated in up to 40%.
• Non-specific and not widely used.
• May be elevated in smokers.

Clinical uses

• Measured at presentation:
• Normal markers do not exclude metastatic disease.
• Measured 1-2 weeks post-radical orchidectomy:
• Normalisation of markers does not indicate absence of disease. Persistent elevation usually indicates residual or metastatic disease (but also elevated in liver dysfunction and hypogonadotrophism).
• Measured during follow-up:
• To assess response to treatment and residual disease.

NB

• 80-85% of testicular tumours have positive markers.
• 85-90% of NSGCTs have raised markers.
• 10-15% of NSGCTs have normal markers.
• Terotomas: 75% have elevated ß-hCG and/or AFP.
• Pure seminomas: do not produce AFP, 0-5% ß-hCG.
• Seminomas: 10-15% produce ß-hCG.
• LDH elevated in metastatic seminomas and teratomas

• Degree of marker elevation directly proportional to tumour burden.
• Markers indicate tumour histology: If AFP elevated in seminoma, tumour has non-seminomatous elements.
• Negative tumour markers becoming positive on follow up usually indicates tumour recurrence.
• Markers become positive earlier than on imaging studies.

S Staging

The S classification is based on the nadir value after orchidectomy.

Sx: markers not available or not performed.

S0: markers within normal limits.

S1: AFP <1000 ng/ml and hCG <5000 mIU/ml and

LDH 1-1.5 x normal upper limit

S2: AFP 1000-10,000 or hCG 5000-50,000 or

LDH 1.5-10 x normal

S3: AFP >10,000 or hCG >50,000 or

LDH >10 x normal