Transcript TESTICULAR TUMOUR

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
Interstitial Cells
Leydig
(Androgen)
Seminiferous Tubules
(200 to 350 tubules)
Supporting
or
Sertoli Cell
Spermatogonia
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.
1.
2.
3.
Nongerminal Neoplasms : ( 5 to 10% )
Specialized gonadal stromal tumor
(a) Leydig cell tumor
(b) Other gonadal stromal tumor
Gonadoblastoma
Miscellaneous Neoplasms
(a) Adenocarcinoma of the rete testis
(b) Mesenchymal neoplasms
(c)
Carcinoid
(d) Adrenal rest “tumor”
II. SECONDARY NEOPLASMS OF TESTIS
A.
B.
Reticuloendothelial Neoplasms
Metastases
III.
PARATESTICULAR NEOPLASMS
A.
B.
C.
D.
E.
Adenomatoid
Cystadenoma of Epididymis
Mesenchymal Neoplasms
Mesothelioma
Metastases
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
(Recent Advances)
Molecular & Genetic Research may
help Future patient with Testicular
Tumours:
Earlier diagnosis
Identify Susceptible Individuals
Testicular Tumour & Molecular Biology
PROTO-ONCOGENES in Germ Cell Tumours
Seminoma &
Embryonal
Carcinoma
Seminoma
Immature
Teratomas
(Shuin et al)
-
N-myc expression
-
c-Ki-ras expression
-
c-erb B-1 expression
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
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
TNM Staging of Testicular Tumour
T0
T1s
T1
T2
=
=
=
=
T3
T4
=
=
No evidence of Tumour
Intratubular, pre invasive
Confined to Testis
Invades beyond Tunica Albuginea
or into Epididymis
Invades Spermatic Cord
Invades Scrotum
N1
N2
N3
=
=
=
Single < 2 cm
Multiple < 5 cm / Single 2-5 cm
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.
2.
3.
4.
Ultrasound - Hypoechoic area
Chest X-Ray - PA and lateral views
CT Scan
Tumour Markers
- AFP
-  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  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
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 Radiotherapy.
Radio-Sensitive.
Treat
with
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
STANDARD CHEMOTHERAPY FOR
NON-SEMINOMATOUS GERM CELL TUMOURS
Chemotherapy
BEP Bleomycin
Toxicity
Pulmonary fibrosis
Etoposide (VP-16)
Myelosuppression
Alopecia
Renal insufficiency (mild)
Secondary leukemia
Cis-platin
Renal insufficiency
Nausea, vomiting
Neuropathy
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
Abdominal Radiotherapy
Follow Up
Stage IIB, IIC, III
B - Bleomycin
E - Etoposide (VP-16)  4 cycles
P - cis-platin
Stable/Regress
F/U
Relapse/Growth
? 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
Therapy of Nonseminomatous Germ Cell Testicular Tumours
Radical Inguinal Orchidectomy
Stage II C (advanced) / III
Complete Response
Observe
BEP  4 cycles
Partial Response
Progress
RPLND
Cancer
V-Vinblastine
I-Ifosfamide
P-cis-platin
VIP or Autologous
Bone marrow
Transplant
Teratoma / Fibrosis
OBSERVE
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 Cisplatinum based Chemotherapy
Current Emphasis is on Diminishing
overall Morbidity of Various Treatment
Modalities