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