Testis carcinoma- staging & tumour markers

1. Ca testis –tumor marker and
staging
Dept of Urology
Govt Royapettah Hospital and Kilpauk Medical College
Chennai
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2. Moderators:
Professors:
• Prof. Dr. G. Sivasankar, M.S., M.Ch.,
• Prof. Dr. A. Senthilvel, M.S., M.Ch.,
Asst Professors:
• Dr. J. Sivabalan, M.S., M.Ch.,
• Dr. R. Bhargavi, M.S., M.Ch.,
• Dr. S. Raju, M.S., M.Ch.,
• Dr. K. Muthurathinam, M.S., M.Ch.,
• Dr. D. Tamilselvan, M.S., M.Ch.,
• Dr. K. Senthilkumar, M.S., M.Ch.
Dept of Urology, GRH and KMC, Chennai. 2

3. Introduction
• Non-seminomatous germ cell tumors (NSGCT)-mostly
• 85% of NSGCT will secrete at least one tumor marker.
• Germ cells in the testis have the potential to transform into a variety
of cell types.
• Germ cells turn into cancer cells,
• Secrete proteins
• Help in the diagnosis, prognosis, treatment and monitoring of testis
cancer.
3
Dept of Urology, GRH and KMC, Chennai.

4. Markers
•AFP (alpha fetoprotein)
•HCG (human chorionic gonadotropin)
•LDH (lactate dehydrogenase)
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Dept of Urology, GRH and KMC, Chennai.

5. ALPHA-FETOPROTEIN (AFP)
• NORMAL RANGE <40 micrograms/L
• T ½ is 5-7 days
• AFP levels are elevated in 50% to 70% of low stage (CS I, IIA, and IIB) NSGCT
and
• 60% to 80% of advanced (CS IIC and III) NSGCT
• secreted by the
• fetal yolk sac
• liver
• gastrointestinal tract
• AFP can be secreted by NSGCT that contain
• embryonal carcinoma, yolk sac tumor or teratoma.
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Dept of Urology, GRH and KMC, Chennai.

6. • Malignancies including with
• Hepatocellular (liver) carcinoma
• Cancer of the stomach
• Pancreas, biliary tract
• Lung
• Non-malignant diseases
• Diseases of the liver
• Ataxic telangiectasia
• Hereditary tyrosinemia.
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Dept of Urology, GRH and KMC, Chennai.

7. HUMAN CHORIONIC GONADOTROPIN (HCG)
• NORMAL RANGE <5 IU/L
• HALF-LIFE 24-36 hours
• HCG is a glycoprotein produced by the placenta to maintain the
corpus luteum during pregnancy.
• Including both seminomas and NSGCT, cancerous cells can transform
into syncytiotrophoblasts (a normal component of the placenta) and
secrete HCG.
7
Dept of Urology, GRH and KMC, Chennai.

8. • 20% to 40% of low-stage NSGCT
• 40% to 60% of advanced NSGCT
• Levels greater than 5,000 IU are usually indicative of NSGCT
• Non seminoma
• higher levels of HCG are associated with a worse prognosis.
• Seminoma
• HCG-producing (approximately 15% of seminomas) has the same prognosis as
seminoma that does not produce HCG.
• Other malignancies
• cancers of the liver
• lung
• pancreas and stomach
8
Dept of Urology, GRH and KMC, Chennai.

9. False positive
• Cross-reactivity of the hCG assay with luteinizing hormone
• Primary hypogonadism.
• Elevated serum hCG results caused by hypogonadism normalize
within 48 to 72 hours after administration of testosterone
• Marijuana use may also cause false-positive hCG results.
9
Dept of Urology, GRH and KMC, Chennai.

10. LACTATE DEHYDROGENASE (LDH)
• NORMAL RANGE 1.5-3.2 MIU/L
• T ½ is 24 hours
• Cellular enzyme found in every tissue in the body.
• Highest concentrations in
• muscle (including skeletal, cardiac and smooth muscle)
• liver
• brain.
10
Dept of Urology, GRH and KMC, Chennai.

11. LDH
• LDH is expressed on chromosome 12p, which is often amplified in
testis cancer cells.
• LDH is less specific for testis cancer than HCG or AFP.
• Elevated in approximately 20% of low-stage GCT and 20% to 60% of
advanced GCT
• Correlated to high tumor burden in seminoma and recurrence in
NSGCT.
• Lymphoma may also cause elevated LDH levels.
11
Dept of Urology, GRH and KMC, Chennai.

12. OTHERS
• PLACENTAL ALKALINE PHOSPHATASE
• Elevated levels present in as many as 40% patients with advanced disease
• Most useful as a marker for “bulk’disease
• Elevated in seminoma
• GGT (Gamma glutamyl transpeptidase):
• Marker of seminoma testis
• Marker for “bulk” disease
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Dept of Urology, GRH and KMC, Chennai.

13. Ca testis …
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Dept of Urology, GRH and KMC, Chennai.

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Dept of Urology, GRH and KMC, Chennai.

15. TNM staging
• The extent of primary tumor is classified after radical orchiectomy
• pTX --Primary tumor cannot be assessed. (If no radical orchiectomy
has been performed, TX is used.)
• pT0-- No evidence of primary tumor
• pTis-- Intratubular germ cell neoplasia (carcinoma in situ)
• pT1--Tumor limited to the testis and epididymis without
vascular/lymphatic invasion.
• Tumor may invade into the tunica albuginea but not the tunica vaginalis
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Dept of Urology, GRH and KMC, Chennai.

16. • pT2--Tumor limited to the testis and epididymis with
vascular/lymphatic invasion, or
• tumor extending through the tunica albuginea with involvement of the tunica
vaginalis
• pT3--Tumor invades the spermatic cord with or without
vascular/lymphatic invasion
• pT4--Tumor invades the scrotum with or without vascular/lymphatic
invasion
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Dept of Urology, GRH and KMC, Chennai.

17. REGIONAL LYMPH NODES
• Clinical (as Determined by Noninvasive)
• NX Regional lymph nodes cannot be assessed
• N0 --No regional lymph node metastasis
• N1 Metastasis with lymph node mass ≤2 cm in greatest dimension;
• or multiple lymph nodes, none more than 2 cm in greatest dimension
17
Dept of Urology, GRH and KMC, Chennai.

18. • N2 Metastasis with lymph node mass, >2 cm
• but not more than 5 cm in greatest dimension; or
• multiple lymph nodes,
• any one mass >2 cm but not more than 5 cm in greatest dimension
• N3 Metastasis with lymph node mass >5 cm in greatest dimension
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Dept of Urology, GRH and KMC, Chennai.

19. LYMPHATIC DRAINAGE
• The retroperitoneum is the initial site of metastatic spread in 70% to 80% of patients
with GCT.
• For right testis tumors
• Inter-aortocaval lymph nodes inferior to the renal vessels,followed by the paracaval and para-
aortic nodes.
• left testis tumors
• The para-aortic lymph nodes, followed by the inter-aortocaval nodes .
• The pattern of lymph drainage in the retroperitoneum is from right to left.
• Contralateral spread is common with right-sided tumors
• Rarely seen with left-sided tumors and usually is associated with bulky disease.
• Retroperitoneal lymphatics drain into the cisterna chyli behind the right renal artery and
right crus of the diaphragm.
• From there, lymphatic spread occurs via the thoracic duct to the posterior mediastinum
and left supraclavicular fossa.
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Dept of Urology, GRH and KMC, Chennai.

20. Pathologic (pN)
• (as Determined by Pathologic Findings of RPLND
without Prior Chemotherapy or Radiotherapy)
• pNX Regional lymph nodes cannot be assessed
• pN0 No regional lymph node metastasis
• pN1 Metastasis with lymph node mass ≤2 cm in greatest dimension
and ≤5 nodes positive, none more than 2 cm in greatest dimension
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Dept of Urology, GRH and KMC, Chennai.

21. • pN2 Metastasis with lymph node mass >2 cm
• not more than 5 cm in greatest dimension;
• or >5 nodes positive, none more than 5 cm;
• or evidence of extranodal extension of tumor
• pN3 Metastasis with lymph node mass >5 cm in greatest dimension
21
Dept of Urology, GRH and KMC, Chennai.

22. DISTANT METASTASIS(M)
• MX -- Distant metastasis cannot be assessed
• M0 --No distant metastasis
• M1 -- Distant metastasis
• M1a Non regional nodal or pulmonary metastasis
• M1b Distant metastasis at site other than non regional lymph nodes or lung
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Dept of Urology, GRH and KMC, Chennai.

23. SERUM TUMORMARKERS (S)
• SX Marker studies unavailable or not performed
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Dept of Urology, GRH and KMC, Chennai.

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Dept of Urology, GRH and KMC, Chennai.

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Dept of Urology, GRH and KMC, Chennai.

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Dept of Urology, GRH and KMC, Chennai.

27. CLINICAL STAGING
• CS I -- clinically confined to the testis
• CS II -- presence of regional (retroperitoneal) lymph node metastasis
• CS III --represents non regional lymph node and/or visceral
metastasis.
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Dept of Urology, GRH and KMC, Chennai.

28. THANK YOU
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Dept of Urology, GRH and KMC, Chennai.

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Dept of Urology, GRH and KMC, Chennai.