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Management of
Testicular Tumours
Dr.Sunil Shroff, MS, FRCS (UK ), D.Urol (Lond.)
Prof & HOD SriRamachandra Medical College & Research Institution,
Chennai
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
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
CROSS SECTION OF TESTIS
Testis
Stroma Seminiferous Tubules
(200 to 350 tubules)
Interstitial Cells Supporting
Spermatogonia
Leydig or
(Androgen) Sertoli Cell
EPIDEMIOLOGY
Incidence : 1.2 per 100,000 (Bombay)
3.7 per 100,000 (USA)
Age : 3 Peaks
- 20-40 yrs. Maximum
- 0 - 10 yrs.
- After - 60 yrs.
Bilaterality : 2 to 3% Testicular Tumour
CLASSIFICATION
I. Primary Neoplasma of
Testis.
A. Germ Cell Tumour
B. Non-Germ Cell Tumour
II. Secondary Neoplasms.
III. Paratesticular Tumours.
I. PRIMARY NEOPLASMS OF TESTIS
A. Germinal Neoplasms : (90 - 95 %)
1. Seminomas - 40%
(a) Classic Typical Seminoma
(b) Anaplastic Seminoma
(c) Spermatocytic Seminoma
2. Embryonal Carcinoma - 20 - 25%
3. Teratoma - 25 - 35%
(a) Mature
(b) Immature
4. Choriocarcinoma - 1%
5. Yolk Sac Tumour
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”
A. Adenomatoid
B. Cystadenoma of Epididymis
C. Mesenchymal Neoplasms
D. Mesothelioma
E. Metastases
II. SECONDARY NEOPLASMS OF TESTIS
A. Reticuloendothelial Neoplasms
B. Metastases
III. PARATESTICULAR NEOPLASMS
AETIOLOGY OF TESTICULAR TUMOUR
1. Cryptorchidism
2. Carcinoma in situ
3. Trauma
4. Atrophy
CRYPTORCHIDISM & TESTICULAR TUMOUR
Risk of Carcinoma
developing in
undescended testis is
14 to 48 times the
normal expected
incidence
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
Testicular Tumour & Molecular Biology
Molecular & Genetic Research may
help Future patient with Testicular
Tumours:
• Earlier diagnosis
• Identify Susceptible Individuals
(Recent Advances)
Testicular Tumour & Molecular Biology
Seminoma &
Embryonal - N-myc expression
Carcinoma
Seminoma - c-Ki-ras expression
Immature
Teratomas - c-erb B-1 expression
PROTO-ONCOGENES in Germ Cell Tumours (Shuin et al)
Testicular Tumour & Molecular Biology
(Recent Advances)
Testicular germ cell tumour show
consistent expression of both:
Parental alleles of H19
IGF-2 genes.
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
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 - β HCG, AFP
Requirements for staging
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
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
Investigation
1. Ultrasound - Hypoechoic area
2. Chest X-Ray - PA and lateral views
3. CT Scan
4. Tumour Markers
- AFP
- β HCG
- LDH
- PLAP
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
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
Tumour Markers
TWO MAIN CLASSES
Onco-fetal Substances : AFP & HCG
Cellular Enzymes : LDH & PLAP
( AFP - Trophoblastic Cells
HCG - Syncytiotrophoblastic Cells )
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
HCG – ( Human Chorionic Gonadotropin )
Has α and β polypeptide chain
NORMAL VALUE: < 1 ng / ml
HALF LIFE of HCG: 24 to 36 hours
RAISED β HCG -
100 % - Choriocarcinoma
60% - Embryonal carcinoma
55% - Teratocarcinoma
25% - Yolk Cell Tumour
7% - Seminomas
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
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
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
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
Treatment of Seminomas
Stage I, IIA, ?IIB –
Radical Inguinal Orichidectomy followed by
radiotherapy to Ipsilateral Retroperitonium &
Ipsilateral Iliac group Lymph nodes (2500-3500 rads)
Bulky stage II and III Seminomas -
Radical Inguinal Orchidectomy is followed by
Chemotherapy
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
Chemotherapy Toxicity
BEP -
Bleomycin Pulmonary fibrosis
Etoposide (VP-16) Myelosuppression
Alopecia
Renal insufficiency (mild)
Secondary leukemia
Cis-platin Renal insufficiency
Nausea, vomiting
Neuropathy
STANDARD CHEMOTHERAPY FOR
NON-SEMINOMATOUS GERM CELL TUMOURS
Left Right
Axial CT Section demonstarating - Left Hydronephrosis, due
to large Para-Aortic Nodal Mass from a Germ cell tumour
Limits of Lymph Nodes Dissection For Right &
Left Sided Testicular Tumours
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
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
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
Therapy of Nonseminomatous Germ Cell Testicular Tumours
PROGNOSIS
Seminoma Nonseminoma
Stage I 99% 95% to 99%
Stage II 70% to 92% 90%
Stage III 80% to 85% 70% to 80%
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

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Management Of Testicular Tumours

  • 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 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 - 20-40 yrs. Maximum - 0 - 10 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 : (90 - 95 %) 1. Seminomas - 40% (a) Classic Typical Seminoma (b) Anaplastic Seminoma (c) Spermatocytic Seminoma 2. Embryonal Carcinoma - 20 - 25% 3. Teratoma - 25 - 35% (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. Adenomatoid B. Cystadenoma of Epididymis C. Mesenchymal Neoplasms D. Mesothelioma E. Metastases II. SECONDARY NEOPLASMS OF TESTIS A. Reticuloendothelial Neoplasms B. Metastases III. PARATESTICULAR NEOPLASMS
  • 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 Molecular & Genetic Research may help Future patient with Testicular Tumours: • Earlier diagnosis • Identify Susceptible Individuals (Recent Advances)
  • 14. Testicular Tumour & Molecular Biology Seminoma & Embryonal - N-myc expression Carcinoma Seminoma - c-Ki-ras expression Immature Teratomas - c-erb B-1 expression PROTO-ONCOGENES in Germ Cell Tumours (Shuin et al)
  • 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. 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 - β HCG, AFP Requirements for staging
  • 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 - β 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 α and β polypeptide chain NORMAL VALUE: < 1 ng / ml HALF LIFE of HCG: 24 to 36 hours RAISED β 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 (2500-3500 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. Chemotherapy Toxicity BEP - Bleomycin Pulmonary fibrosis Etoposide (VP-16) Myelosuppression Alopecia Renal insufficiency (mild) Secondary leukemia Cis-platin Renal insufficiency Nausea, vomiting Neuropathy STANDARD CHEMOTHERAPY FOR NON-SEMINOMATOUS GERM CELL TUMOURS
  • 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. 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 Therapy of Nonseminomatous Germ Cell Testicular Tumours
  • 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