Management Of Testicular Tumours

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 -  HCG, AFP Requirements for staging

TNM Staging of Testicular Tumour T 0 = No evidence of Tumour T 1s = Intratubular, pre invasive T 1 = Confined to Testis T 2 = Invades beyond Tunica Albuginea or into Epididymis T 3 = Invades Spermatic Cord T 4 = Invades Scrotum N 1 = Single < 2 cm N 2 = Multiple < 5 cm / Single 2-5 cm N 3 = 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 -  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 - 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

Management Of Testicular Tumours

by fondas vak on Feb 04, 2010

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