1. Management of Testicular Tumours
Dr.Sunil Shroff, MS, FRCS (UK ), D.Urol (Lond.)
Prof & HOD SriRamachandra Medical College & Research Institution, Chennai

2. TESTICULAR TUMOUR 1% of all Malignant Tumour
Affects young adults - 20 to 40 yrs - when Testosterone Fluctuations are maximum
90% to 95% of all Testicular tumours from germ cells
99% of all Testicular Tumours are malignant.
Causes Psychological & Fertility Problems in young

3. Survival in Testicular Tumours
Improved overall survival in last 15 to 20 years due to -
Better understanding of Natural History and Pathogenesis of disease
Reliable Tumour Markers
Cis-platinum based chemotherapy

4. CROSS SECTION OF TESTIS
Stroma Seminiferous Tubules
(200 to 350 tubules)
Interstitial Cells Supporting Spermatogonia
Leydig or
(Androgen) Sertoli Cell

5. EPIDEMIOLOGY Incidence : 1.2 per 100,000 (Bombay)
3.7 per 100,000 (USA)
Age : 3 Peaks
yrs. Maximum
yrs.
- After - 60 yrs.
Bilaterality : 2 to 3% Testicular Tumour

6. CLASSIFICATION I. Primary Neoplasma of Testis. A. Germ Cell Tumour
B. Non-Germ Cell Tumour
II. Secondary Neoplasms.
III. Paratesticular Tumours.

7. I. PRIMARY NEOPLASMS OF TESTIS
A. Germinal Neoplasms : ( %)
1. Seminomas - 40%
(a) Classic Typical Seminoma
(b) Anaplastic Seminoma
(c) Spermatocytic Seminoma
2. Embryonal Carcinoma %
3. Teratoma %
(a) Mature
(b) Immature
4. Choriocarcinoma - 1%
5. Yolk Sac Tumour

8. I. PRIMARY NEOPLASMS OF TESTIS
B. Nongerminal Neoplasms : ( 5 to 10% )
1. Specialized gonadal stromal tumor
(a) Leydig cell tumor
(b) Other gonadal stromal tumor
2. Gonadoblastoma
3. Miscellaneous Neoplasms
(a) Adenocarcinoma of the rete testis
(b) Mesenchymal neoplasms
(c) Carcinoid
(d) Adrenal rest “tumor”

9. A. Reticuloendothelial Neoplasms B. Metastases
II. SECONDARY NEOPLASMS OF TESTIS
A. Reticuloendothelial Neoplasms
B. Metastases
III. PARATESTICULAR NEOPLASMS
A. Adenomatoid
B. Cystadenoma of Epididymis
C. Mesenchymal Neoplasms
D. Mesothelioma
E. Metastases

10. AETIOLOGY OF TESTICULAR TUMOUR
1. Cryptorchidism
2. Carcinoma in situ
3. Trauma
4. Atrophy

11. CRYPTORCHIDISM & TESTICULAR TUMOUR
Risk of Carcinoma developing in undescended testis is
14 to 48 times the normal expected incidence

12. CRYPTORCHIDISM & TESTICULAR TUMOUR
The cause for malignancy are as follows:
Abnormal Germ Cell Morphology
Elevated temperature in abdomen & Inguinal region as opposed to scrotum
Endocrinal disturbances
Gonadal dysgenesis

13. Testicular Tumour & Molecular Biology
(Recent Advances)
Molecular & Genetic Research may help Future patient with Testicular Tumours:
Earlier diagnosis
Identify Susceptible Individuals

14. Testicular Tumour & Molecular Biology
PROTO-ONCOGENES in Germ Cell Tumours (Shuin et al)
Seminoma &
Embryonal - N-myc expression
Carcinoma
Seminoma - c-Ki-ras expression
Immature
Teratomas - c-erb B-1 expression

15. Testicular Tumour & Molecular Biology (Recent Advances)
Testicular germ cell tumour show consistent expression of both:
Parental alleles of H19
IGF-2 genes.

16. Clinical Staging of Testicular Tumour
Staging A or I - Tumour confined to testis.
Staging B or II - Spread to Regional nodes.
IIA - Nodes <2 cm in size or < 6 Positive Nodes
IIB - 2 to 5 cm in size or > 6 Positive Nodes
IIC - Large, Bulky, abd.mass usually > 5 to 10 cm
Staging C or III - Spread beyond retroperitoneal Nodes or Above Diaphragm or visceral disease

17. Requirements for staging
To properly Stage Testicular Tumours following
are pre-requisites:
(a) Pathology of Tumour Specimen
(b) History
(c) Clinical Examination
(d) Radiological procedure - USG / CT / MRI / Bone Scan
(e) Tumour Markers -  HCG, AFP

18. TNM Staging of Testicular Tumour
T0 = No evidence of Tumour
T1s = Intratubular, pre invasive
T1 = Confined to Testis
T2 = Invades beyond Tunica Albuginea or into Epididymis
T3 = Invades Spermatic Cord
T4 = Invades Scrotum
N1 = Single < 2 cm
N2 = Multiple < 5 cm / Single 2-5 cm
N3 = Any node > 5 cm
Epididymis or Scrotal skin – Lymph drainage to Inguinal Nodes

19. Pathogenesis & Natural History of Testicular Tumour
Course of Spread of Germ Cell Tumours are predictible once Histology of Tumour cofirmed
Lymphatic Spread has a set pattern depending on side of Tumour
Seminoma may have non-seminomatous metastasis
High Grade Tumours spread by both Vascular invasion & via Lymphatics

20. Investigation 1. Ultrasound - Hypoechoic area
2. Chest X-Ray - PA and lateral views
3. CT Scan
4. Tumour Markers
- AFP
-  HCG
- LDH
- PLAP

21. CLINICAL FEATURES
Painless Swelling of One Gonad
Dull Ache or Heaviness in Lower Abdomen
10% - Acute Scrotal Pain
10% - Present with Metatstasis
- Neck Mass / Cough / Anorexia / Vomiting / Back Ache/ Lower limb swelling
5% - Gynecomastia
Rarely - Infertility

22. DICTUM FOR ANY SOLID SCROTAL SWELLINGS
All patients with a solid, Firm Intratesticular Mass that cannot be Transilluminated should be regarded as Malignant unless otherwise proved

23. Tumour Markers TWO MAIN CLASSES Onco-fetal Substances : AFP & HCG
Cellular Enzymes : LDH & PLAP
( AFP - Trophoblastic Cells
HCG - Syncytiotrophoblastic Cells )

24. AFP –( Alfafetoprotein )
NORMAL VALUE: Below 16 ngm / ml
HALF LIFE OF AFP – 5 and 7 days
Raised AFP :
Pure embryonal carcinoma
Teratocarcinoma
Yolk sac Tumour
Combined Tumour
REMEMBER: AFP Not raised is Pure Choriocarcinoma or Pure Seminoma

25. HCG – ( Human Chorionic Gonadotropin )
Has  and  polypeptide chain
NORMAL VALUE: < 1 ng / ml
HALF LIFE of HCG: 24 to 36 hours
RAISED  HCG -
100 % - Choriocarcinoma
60% - Embryonal carcinoma
55% - Teratocarcinoma\
25% - Yolk Cell Tumour
7% - Seminomas

26. ROLE OF TUMOUR MARKERS
Helps in Diagnosis - 80 to 85% of Testicular Tumours have Positive Markers
Most of Non-Seminomas have raised markers
Only 10 to 15% Non-Seminomas have normal marker level
After Orchidectomy if Markers Elevated means Residual Disease or Stage II or III Disease
Elevation of Markers after Lymphadenectomy means a STAGE III Disease

27. ROLE OF TUMOUR MARKERS cont...
Degree of Marker Elevation Appears to be Directly Proportional to Tumour Burden
Markers indicate Histology of Tumour:
If AFP elevated in Seminoma - Means Tumour has Non-Seminomatous elements
Negative Tumour Markers becoming positive on follow up usually indicates -
Recurrence of Tumour
Markers become Positive earlier than X-Ray studies

28. PRINCIPLES OF TREATMENT
Treatment should be aimed at one stage above the clinical stage
Seminomas - Radio-Sensitive. Treat with Radiotherapy.
Non-Seminomas are Radio-Resistant and best treated by Surgery
Advanced Disease or Metastasis - Responds well to Chemotherapy

29. PRINCIPLES OF TREATMENT
Radical INGUINAL ORCHIDECTOMY is Standard first line of therapy
Lymphatic spread initially goes to
RETRO-PERITONEAL NODES
Early hematogenous spread RARE
Bulky Retroperitoneal Tumours or Metastatic Tumors Initially “DOWN-STAGED” with CHEMOTHERAPY

30. Treatment of Seminomas
Stage I, IIA, ?IIB –
Radical Inguinal Orichidectomy followed by radiotherapy to Ipsilateral Retroperitonium & Ipsilateral Iliac group Lymph nodes ( rads)
Bulky stage II and III Seminomas -
Radical Inguinal Orchidectomy is followed by Chemotherapy

31. Treatment of Non-Seminoma
Stage I and IIA:
RADICAL ORCHIDECTOMY
followed by RETROPERITONEAL LYMPH NODES DISSECTION
Stage IIB:
RPLND with possible ADJUVANT CHEMOTHERAPY
Stage IIC and Stage III Disease:
Initial CHEMOTHERAPY followed by SURGERY for Residual Disease

32. STANDARD CHEMOTHERAPY FOR NON-SEMINOMATOUS GERM CELL TUMOURS
Chemotherapy Toxicity
BEP -
Bleomycin Pulmonary fibrosis
Etoposide (VP-16) Myelosuppression
Alopecia
Renal insufficiency (mild)
Secondary leukemia
Cis-platin Renal insufficiency
Nausea, vomiting
Neuropathy

33. Left Right
Axial CT Section demonstarating - Left Hydronephrosis, due to large Para-Aortic Nodal Mass from a Germ cell tumour

34. Limits of Lymph Nodes Dissection For Right &
Left Sided Testicular Tumours

35. THERAPY OF PATIENT WITH SEMINOMA
Stage I, IIA, ? IIB Stage IIB, IIC, III
B - Bleomycin
Abdominal Radiotherapy E - Etoposide (VP-16)  4 cycles
P - cis-platin
Follow Up Stable/Regress Relapse/Growth
F/U ? RPLND
? Chemotherapy
? XRT

36. Therapy of Nonseminomatous Germ Cell Testicular Tumours
Radical Inguinal Orchidectomy
Stage I, II (minimum)
RPLND
Stage I, II B1 Stage II B2
Observe BEP  2 cycles
Bleomycin
Etoposide
Cis-platin

37. Therapy of Nonseminomatous Germ Cell Testicular Tumours
Radical Inguinal Orchidectomy
Stage II C (advanced) / III
BEP  4 cycles
Complete Response Partial Response Progress
Observe RPLND VIP or Autologous
Bone marrow
Transplant
Cancer Teratoma / Fibrosis
V-Vinblastine
I-Ifosfamide OBSERVE
P-cis-platin

38. PROGNOSIS Seminoma Nonseminoma Stage I 99% 95% to 99%
Stage II 70% to 92% 90%
Stage III 80% to 85% 70% to 80%

39. CONCLUSION
Improved Overall Survival of Testicular Tumour due to Better Understanding of the Disease, Tumour Markers and Cis-platinum based Chemotherapy
Current Emphasis is on Diminishing overall Morbidity of Various Treatment Modalities