Download MBBS Urology Presentations 10 Testicular Tumors Lecture Notes

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Department of Urology

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T

E S T I

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C

U L AR TUMORS:

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? Testicular cancer accounts for

? Testicular cancer although

only about 1% of all human

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rare, is the most common

neoplasms.

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malignancy in men in 15-35

years age group and

accounts for approximately

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23% of all cancers in this

group.
WHO CLASSIFICATION OF TESTICULAR

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TUMORS:

Germ cell tumors:

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Precursor lesions- intratubular malignant germ cell tumor (carcinoma

in situ)

Tumors of one histologic type (pure forms)

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Seminoma

variant- seminoma with syncitiotrophoblastic cells

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Spermatocytic seminoma

variant- spermatocytic seminoma with sarcoma

Embryonal carcinoma

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Yolk sac tumor

Polyembryoma

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Trophoblastic tumors- choriocarcinoma

Teratoma

Mature teratoma

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Dermoid cyst

Immature teratoma

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Teratoma with malignant areas

Mixed tumors

CLASSIFICATION (CONT...)

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Sex cord/ Gonadal Stromal Tumors:

-Pure forms
Leydig's cell tumor

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Sertoli's cell tumor
large cell calcifying
lipid rich cell

-Granulosa cell tumor

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Adult type granulosa cell tumor
Juvenile type granulosa cell tumor

-Tumors of thecoma/ fibroma group

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-Incompletely diffrentiated sex cord/ gonadal stromal tumors

-Mixed forms.
CLASSIFICATION (CONT...)

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-Unclassified forms

-Tumors containing both germ cell and sex cord/ gonadal stromal

elements

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-Gonadoblastoma
-Mixed germ cell- sex cord/ gonadal stromal tumors,

unclassified

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-Miscellaneous tumors
-Carcinoid tumors
-Tumors of ovarian epithelial types.

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CLASSIFICATION (CONT...)

-Lymphoid and hematopoietic tumors:

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-Lymphoma
- Plasmacytoma
- Leukemia

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-Tumors of collecting duct and rete:

-Adenoma
-Carcinoma

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-Tumors of tunica, epididymis, spermatic cord, supporting

structures, and appendices:

-Adenomatoid tumor

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- Mesothelioma
- Adenoma
-Carcinoma
-Melanotic neuroectodermal tumor.
CLASSIFICATION (CONT...)

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-Soft tissue tumors,

-Unclassified tumors, and

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-Secondary tumors.

GERM CELL TUMORS- EPIDEMIOLOGY

Low in

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Life time

probability of

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Africa

developing

and Asia.

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testicular

cancer is 0.2%.

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The average annual age

adjusted rate is highest in

Denmark, Norway,

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Switzerland Germany and

Intermediate

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New Zealand.

in U.S and

U.K.

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GERM CELL TUMORS- EPIDEMIOLOGY

AGE:

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RACIAL FACTORS:

?These neoplasms

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?More common in

are the most

white population

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common

solid

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than in blacks.

tumors of men

age 20 ? 40 years

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and second most

common of men

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age 15 ? 19

years.

GERM CELL TUMOR- EPIDEMIOLOGY

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The evidence for a

predominantly genetic

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influence is not

overwhelming.

GENETIC FACTORS:-

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The 2 ? 3% incidence of

bilateral tumors may

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suggest the potential

importance of genetic and

(or) congenital factors.

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GERM CELL TUMORS- ETIOLOGY

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CRYPTORCHIDISM:

7-10% of patients with testicular tumors have prior

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history of cryptorchidism.

The relative risk of developing a testicular cancer in

maldescent testis is 3 to 14 times the normal expected

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incidence.

5-10% of patients with a history of cryptorchidism develop

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malignancy in the contralateral normally descended testes.

25% of patients with bilateral cryptorcidism and a history of

tetsis cancer develop second GCT.

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GERM CELL TUMORS- ETIOLOGY

TRAUMA:

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ATROPHY:

? There is little to

? Causative role of

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suggest a cause and

atrophy remains

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effect relationship in

speculative.

humans.

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? nonspecific or mumps

associated atrophy of

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? Infact trauma in an

the testis has been

enlarged testes is an

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suggested as a potential

event that prompts

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causative factor in

medical evaluation.

testicular cancer.

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GERM CELL TUMORS- ETIOLOGY

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Offspring of

women exposed to

Exogenous

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diethylstilbestrol

estrogen

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or oral

administration has

HORMONES:

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contraceptives has

also been linked to

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relative risk rate of the induction of

developing

leydig's cell

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testicular cancer

tumors.

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of 2.8 - 5.3%.

GERM CELL TUMOR- CLINICAL MANIFESTATIONS:

The usual presentation of a testicular tumor is

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a nodule or painless swelling in one gonad.

30-40% may complain of a

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On rare occasions,

dull ache or heavy

infertility is the presenting

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sensation in the lower

complaint.

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abdomen, anal area, or

scrotum.

In 10%, acute pain is the

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presenting complain.

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GERM CELL TUMORS- CLINICAL MANIFESTATIONS

In 10% of patients, the presenting manifestation may be due to metastasis:-

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A neck mass

? Supraclavicular lymph node metastasis.

Gastrointestinal disturbances

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? Retroduodenal metastasis

Lumbar back pain

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? Involving psoas muscle or nerve roots

Bone pain

? Skeletal metastasis

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Central and peripheral nervous system manifestations

? Cerebral, spinal cord, or peripheral root involvement

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Unilateral or bilateral lower extremity

? Iliac or caval obstruction.

GERM CELL TUMORS- PHYSICAL EXAMINATION

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BIMANUAL EXAMINATION:

Beginning with the normal contralateral testis.

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Any firm, hard, or fixed area should be considered

suspicious.

Testicular tumors tend to remain ovoid, being limited

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by the tough investing tunica albuginea.

A hydrocele may be present and increases the

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difficulty of palpation.
GERM CELL TUMOR-

Scrotal Sonography:

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USGof the scrotum is basically an extension of the physical

examination.

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Any hypoechoic area within the tunica albuginea is

markedly suspicious for testicular cancer.

In patients with a diagnosis of EGCT, ultrasound of the

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testis is mandatory to be certain that one is not dealing

with a primary GCT.

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GERM CELL TUMORS- IMAGING STUDIES

Chest Radiography:

?Postero-anterior and lateral chest

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radiographs: Metastatic workup

Chest CT:

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?Indicated in patients with

abnormal X-ray scans.
GERM CELL TUMORS- IMAGING

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Abdominal CT:

Most effective means to identify

retroperitoneal lymph node involvement.

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Excellent for visualization of kidney, ureters,

retro-crural space in the para-aortic region.

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However cannot sufficiently distinguish

between fibrosis, teratoma, and malignancy

by size criteria alone.

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MRI:

Testicular tumors are hypointense on T2

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weighted images, and show brisk and early

enhancement after I.V Gadolinium.

PET:

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To detect radiographic abnormalities after

chemotherapy.

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Neither PET nor CT has the ability to detect

microscopic nodal disease.
Applied to body fluid and tissue sections.

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Oncofetal substances: associated with

embryonic development (AFP, HCG),

Cellular enzymes: LDH, PLAP.

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Capable of detecting small tumor burdens

(105 cells) that are not detectable by

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currently available imaging techniques.

AFP:

Not produced by pure choriocarcinoma or

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pure seminoma.

HCG:

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Choriocarcinoma (all patients),

Embryonal carcinoma (40-60%),

Pure seminoma (5-10%).

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LDH:
Has low specificity.

There is a direct relationship between tumor

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burden and LDH levels.

PLAP:
Raised in 40% of patients with advanced disease.
GGTP:

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Raised in one third of patients with active

seminoma.

CD30:

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? possible marker for embryonal carcinoma.

RADICAL INGUINAL ORCHIDECTOMY(HIGH

TYPE)

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TESTIS SPARING SURGERY- Highly

controversial

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GERM CELL TUMORS : STAGING

The American Joint Committee on Cancer staging for GCTs:

Primary Tumor (T):

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pTx: primary tumor cannot be assessed.

pT0: no evidence of primary tumor

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pTis: intratubular germ cell neoplasia.

pT1: tumor limited to the testis and epididymis and no vascular or lymphatic invasion.

pT2: tumor limited to the testis and epididymis with vascular or lymphatic invasion or tumor

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extending through the tunica albuginea with involvement of tunica vaginalis.

pT3: tumor invades the spermatic cord with or without vascular/ lymphatic invasion.

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pT4: tumor invades the scrotum.

GERM CELL TUMORS : STAGING

N2:

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N1:

lymph

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lymph

node mass

node

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more than

mass

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2cm but

2cm or

not more

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less in

than 5 cm

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in

N3:

greatest

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lymph

Region

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Nx:

N0:

greatest

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no

dimensio

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dimension,

node

al

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regional

lymph

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regional

n or

or

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mass

lymph

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nodes

lymph

multiple

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multiple

more

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nodes

lymph

cannot

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node

lymph

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than

metastas

node

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node

5cm in

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(N)

be

masses,

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assessed.

is.

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masses,

greatest

none

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anyone

dimensio

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more

mass

greater

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n.

than

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than 2 cm

2cm in

but not

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greatest

more than

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dimensio

5 cm in

n.

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greatest

dimension.
GERM CELL TUMOR STAGING:

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Distant

M0: no

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metastasis

evidence of

(M)

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distant

metastasis.

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M1: non

M2:

regional nodal

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nonpulmonary

or pulmonary

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visceral

metastasis.

metastasis.

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GERM CELL TUMOR STAGING:

Serum tumor markers (S)

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LDH

hCG (mIU/ml)

AFP (ng/ml)

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S0

N

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N

N

S1

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<1.5 x N

< 5000

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< 1000

S2

1.5-10 N

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5000 ? 50000

1000-10,000

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S3

> 10 N

>50,000

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> 10,000
PROGNOSIS

SEMINOMA

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Good Prognosis:

Intermediate prognosis:

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? Any primary site

? Any primary site

? No pulmonary or visceral

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? Nonpulmonary visceral

metastasis

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metastasis

? AFP: Normal;

? AFP: Normal;

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Poor prognosis:

? hCG: Any value

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? hCG: Any value

No patients classified as

? LDH: Any value

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? LDH: Any value

poor prognosis

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PROGNOSIS

NONSEMINOMA

Good Prognosis:

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Intermediate prognosis:

Poor prognosis:

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? Testis or retroperitoneal

? Testis or retroperitoneal

Any of the following

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primary

primary,

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criteria:

? No pulmonary or visceral

? No nonpulmonary

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? Mediastinal primary

metastasis

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visceral metastasis

? Nonpulmonary visceral

? AFP<1000ng/ml;

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? Any of: AFP1000-

metastasis

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hCG<5000IU/L;

10,000ng/ml; hCG5000-

? AFP>10,000ng/ml;

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LDH<1.5times upper

50,000IU/L; LDH1.5-10

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hCG>50,000IU/L;

limit.

times upper limit

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LDH>10 times upper

limit.

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TREATMENT

Stage 1 T1-

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3N0M0S0

Spematocytic

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seminoma:

age >65yrs;

Typical and

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exclude

anaplastic

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sarcoma,

seminoma

benign tumor

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Risk factors

No adjuvant

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primary tumor

tratment

>6cm; vascular

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or lymphatic

invasion

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No risk factors

Risk factors

present

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Radiation- low

Chemotherapy

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surveillance

dose, abdominal

single agent-

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and pelvic

carboplatin
Radiation therapy:

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Today most centers administer 25Gy to para-

aortic nodes only.

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This has a 5 year survival in excess of 95%.

Primary Chemotherapy:

Single agent carboplatin compare favorably

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with adjuvant radiation therapy.

2 courses of carboplatin were associated with

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no relapse and favorable toxicity profile.

Surveillance:
Appropriate for patients with:
1. tumors smaller than 6 cm,

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2. absence of vascular invasion, and
3. normal hCG levels.
in motivated and reliable patients.

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GERM CELL TUMORS

SEMINOMA: STAGE I A AND I B

Radiation-

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abdominal and

Stage IIA and

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pelvic

IIB seminoma

Chemotherapy-

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if lymph nodes

close to kidney

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GERM CELL TUMORS

SEMINOMA: STAGE I A AND I B

Radiation therapy:

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N1 disease receive 30 Gy, and N2 disease receive 35 Gy.
Patients with stage II seminoma have 5 year survival rates

of 70% to 92%.

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Chemotherapy:
Irradiation to kidney is avoided- parenchyma is sensitive.
So, chemotherapy is preferred in this region.

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GERM CELL TUMORS

Stage IIC and III seminoma

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Chemotherapy- cisplatin based

Residual retroperitoneal mass following chemotherapy

Diffuse desmoplastic

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reaction- observation

Descrete well deliniated mass>3cm

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Surgical resection

Histology-

Histology- germ cell

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necrosis/fibrosis

tumor

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observation

Salvage chemotherapy

GERM CELL TUMORS

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Cisplatin based chemotherapy:
>90% of patients achieve a complete response.

Residual masses are resected if on CT scan:

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-if they are well delineated,
-distinct from surrounding structures, and
-diameter is larger than 3 cm.

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NON-SEMINOMATOUS GERM CELL TUMORS

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STAGE 1: TREATMENT PRINCIPLES.

Stage 1

Risk factors: T2 or higher, embryonal>40%,

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vascular/lymphatic invasion.

Stage 1S

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Risk factors

Chemotherapy

absent

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Risk factors present

BEP 3 cycles

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Primary

surveillance

Modified RPLND

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chemotherapy

BEP 3 cycles

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Stage N0

Stage N1

Stage N2

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Adjuvant

observation

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observation

chemotherapy

BEP 2 cycles

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NONSEMINOMATOUS GERM CELL TUMORS

STAGE 1: TREATMENT PRINCIPLES

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Retro-peritoneal lymph node dissection:
? Capable of eradicating resectable disease in the majority

of N1-N2 tumors.

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? 5 year survival for stage 1 is 95%.
? 5-10% experience relapse: high cure rates with

chemotherapy.

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Modified (template) RPLND:
? Complete dissection in the most likely area, and

modification in less likely area.

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? Ejaculation is preserved in 100%, and fertility noted in

75% of patients.
NONSEMINOMATOUS GERM CELL TUMORS

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STAGE 1: TREATMENT PRINCIPLES

Primary radiation therapy:
? 5 year survival for stage 1: 80-95% when chemotherapy is

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used to treat relapses.

? Relapse rate after radiation therapy: 24%.

The main objections to radiation therapy:

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? Inaccuracy of clinical staging,
? Lack of survival data,
? Prior radiation makes it difficult for future surgical or

pharmacological intervention, and

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? Risk of second malignancy: 18% in 25 years.

NONSEMINOMATOUS GERM CELL TUMORS

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STAGE 1: TREATMENT PRINCIPLES

Prognostic factors for clinical stage 1 tumors:
? Invasion of testicular veins,
? Invasion of lymphatics,

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? Absence of yolk sac elements,
? presence of embryonal cell carcinoma, and
? Angiogenesis: factor VIII stain positive.
NONSEMINOMATOUS GERM CELL TUMORS

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STAGE 1: TREATMENT PRINCIPLES

Surveillance:
Surveillance is indicated in stage 1 disease:-
? without any risk factors for relapse,

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? in motivated patients, and
? who fully understands the risk of failure to comply.

NONSEMINOMATOUS GERM CELL

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TUMORS

STAGE 1: TREATMENT PRINCIPLES

Surveillance protocol:

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Physical examination, chest radiographs, and

tumor markers: monthly for 1st year, every 2

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months for second year, and every 3-6

months thereafter.

CT abd: every 2-3 months for the first 2

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years, and every 6 months thereafter.

Finally, surveillance is necessary for

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minimum of 5 years, possibly 10 years after

orchiectomy.

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NONSEMINOMATOUS GERM CELL TUMORS

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STAGE 1: TREATMENT PRINCIPLES

Primary chemotherapy:
2 cycles of bleomycin, cisplatin, and etoposide are used.
5 year survival: 95%-100%.

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Added advantage of treating metastatic disease outside

the retroperitoneum.

Suitable for centers where expertise for RPLND are not

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available.

NONSEMINOMATOUS GERM CELL TUMORS

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STAGE I A AND I B: TREATMENT PRINCIPLES

Stage IIA and

IIB

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RPLND-

Primary

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bilateral

chemotherapy

BEP- 3 cycles

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Minimal nodal

Nodal

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involvement

involvement

<2cm

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>2cm

Adjuvant

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surveillance

chemotherapy

BEP- 2 cycles

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NONSEMINOMATOUS GERM CELL TUMORS

STAGE I A AND I B: TREATMENT PRINCIPLES

RPLND:

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A complete bilateral lymphadenectomy is recommended.

? Patients with minimal retroperitoneal disease on RPLND:

careful follow-up.

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? Patients with more extensive disease on RPLND: two

cycles of adjuvant chemotherapy.

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NONSEMINOMATOUS GERM CELL TUMORS

STAGE I A AND I B: TREATMENT PRINCIPLES

Primary chemotherapy:

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? If nodes are larger than 3 cm on CT.
? Avoids ejaculatory failure.
Disadvantages: azoospermia, secondary malignancy.

17% of stage IIa patients and 39% of stage IIb patients

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require RPLND after chemotherapy for relapse.
NONSEMINOMATOUS GERM CELL TUMORS

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Stage IIC and Stage III

Good risk disease

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Poor risk

disease

Chemotherapy

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Chemotherapy BEP- 3 cycles

ifosfamide

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substitutes

etoposide

Response to

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Resolution of disease

Residual retroperitoneal mass-

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Persistent elevation

chemotherapy

bilateral RPLND with tumorectomy

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of tumor markers

poor, or elevated

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tumor markers-

Exclude false

observation

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Histology- necrosis,

Germ cell

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Salvagee

fibrosis, teratoma

tumor

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positive-

chemotherapy

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chemotherapy

Recurrent disease

observation

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Salvage

Inadequate

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chemotherapy

response

Salvage chemotherapy

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Desperation

surgery

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Complete

No response;

response

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elevated tumor

markers

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observation

Desperation

surgery

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NONSEMINOMATOUS GERM CELL TUMORS

STAGE I C AND I I: TREATMENT PRINCIPLES

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Contraindication to adjunctive surgery in patients after

chemotherapy: The presence of elevated levels of tumor

markers.

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Salvage Chemotherapy:
? residual cancer that has been resected after

chemotherapy,

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? who do not respond to traditional courses of induction

therapy.
NONSEMINOMATOUS GERM CELL TUMORS

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STAGE I C AND I I: TREATMENT PRINCIPLES

Patients who failed initial chemotherapy regimens:
Ifosfamide in combination with vinblastine and cisplatin.

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Patients who failed 1st and 2nd line therapy:
Autologous bone marrow transplant or stem cell support

with high dose chemotherapy regimens.

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THANKS