management of testicular tumours dr.sunil shroff, ms, frcs (uk ), d.urol (lond.) prof & hod...
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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
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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
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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
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CROSS SECTION OF TESTIS
Testis
Stroma Seminiferous Tubules
(200 to 350 tubules)
Interstitial Cells Supporting
SpermatogoniaLeydig or(Androgen) Sertoli Cell
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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
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CLASSIFICATION
I. Primary Neoplasma of Testis.
A. Germ Cell Tumour B. Non-Germ Cell Tumour
II. Secondary Neoplasms.
III. Paratesticular Tumours.
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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
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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”
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A. AdenomatoidB. Cystadenoma of EpididymisC. Mesenchymal NeoplasmsD. MesotheliomaE. Metastases
II. SECONDARY NEOPLASMS OF TESTIS
A. Reticuloendothelial NeoplasmsB. Metastases
III. PARATESTICULAR NEOPLASMS
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AETIOLOGY OF TESTICULAR TUMOUR
1. Cryptorchidism
2. Carcinoma in situ
3. Trauma
4. Atrophy
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CRYPTORCHIDISM & TESTICULAR TUMOUR
Risk of Carcinoma developing in
undescended testis is
14 to 48 times the normal expected
incidence
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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
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Testicular Tumour & Molecular Biology
Molecular & Genetic Research may help Future patient with Testicular Tumours:
• Earlier diagnosis
• Identify Susceptible Individuals
(Recent Advances)
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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)
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Testicular Tumour & Molecular Biology (Recent Advances)
Testicular germ cell tumour show consistent expression of
both:
Parental alleles of H19
IGF-2 genes.
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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
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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
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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
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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
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Investigation
1. Ultrasound - Hypoechoic area2. Chest X-Ray - PA and lateral views3. CT Scan4. Tumour Markers
- AFP- HCG- LDH- PLAP
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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
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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
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Tumour Markers
TWO MAIN CLASSES
Onco-fetal Substances : AFP & HCG
Cellular Enzymes : LDH & PLAP
( AFP - Trophoblastic Cells
HCG - Syncytiotrophoblastic Cells )
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Left Right
Axial CT Section demonstarating - Left Hydronephrosis, due to large Para-Aortic Nodal Mass from a Germ cell tumour
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Limits of Lymph Nodes Dissection For Right & Left Sided Testicular Tumours
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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
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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
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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
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PROGNOSIS
Seminoma Nonseminoma
Stage I99% 95% to 99%
Stage II 70% to 92% 90%
Stage III 80% to 85% 70% to 80%
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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