management of testicular tumours
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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
SpermatogoniaLeydig 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. Gonadoblastoma3. Miscellaneous Neoplasms
(a) Adenocarcinoma of the rete testis
(b) Mesenchymal neoplasms(c) Carcinoid(d) Adrenal rest “tumor”
A. AdenomatoidB. Cystadenoma of EpididymisC. Mesenchymal NeoplasmsD. MesotheliomaE. Metastases
II. SECONDARY NEOPLASMS OF TESTIS
A. Reticuloendothelial NeoplasmsB. 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 expressionCarcinoma
Seminoma - c-Ki-ras expression ImmatureTeratomas - 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 NodesIIB - 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 - 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 EpididymisT3 = Invades Spermatic Cord
T4 = Invades Scrotum
N1 = Single < 2 cm
N2 = Multiple < 5 cm / Single 2-5 cm
N3 = Any node > 5 cmEpididymis 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 area2. Chest X-Ray - PA and lateral views3. CT Scan4. 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 / mlHALF LIFE OF AFP – 5 and 7 days
Raised AFP : Pure embryonal carcinomaTeratocarcinoma 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 Tumour7% - 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 BurdenMarkers indicate Histology of Tumour: If AFP elevated in Seminoma - Means Tumour has Non-Seminomatous elementsNegative Tumour Markers becoming positive on follow up usually indicates -Recurrence of TumourMarkers 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 SeminomasStage 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-SeminomaStage I and IIA: RADICAL ORCHIDECTOMYfollowed 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) MyelosuppressionAlopeciaRenal insufficiency (mild)Secondary leukemia
Cis-platin Renal insufficiencyNausea, vomitingNeuropathy
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 - BleomycinAbdominal 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 cyclesBleomycinEtoposideCis-platin
Radical Inguinal Orchidectomy
Stage II C (advanced) / III
BEP 4 cyclesComplete Response Partial Response Progress
Observe RPLND VIP or AutologousBone marrowTransplant
Cancer Teratoma / Fibrosis
V-VinblastineI-Ifosfamide OBSERVEP-cis-platin
Therapy of Nonseminomatous Germ Cell Testicular Tumours
PROGNOSIS
Seminoma Nonseminoma
Stage I99% 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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