2. Testicular Tumours
Incidence
Classification
Etiology
Spread of tumour
Clinical Staging
Clinical features
Differential Diagnosis
Investigations
Treatment
Follow up schedule
3. Incidence
Testicular tumors are rare
1-2% of all malignant tumors.
Age – most common solid tumor of men between 20-40 years
Race – White : Black = 4:1 in U.S.
Side – Right > Left
Socio-economic status – high : low = 2:1
Geographical
Highest in Scandinavia, Germany, Switzerland
Intermediate – USA & UK
Low – Africa and Asia
4. Benign lesions represent a greater percentage of cases in children
than adults.
Most curable solid neoplasm.
Age – 3 peaks
3 – 4 yrs.
20 – 40 yrs.
above 60 yrs.
Testicular cancer is one of the few neoplasms associated with
accurate serum markers.
5. Etiology
Cryptorchidism : Risk of carcinoma in UDT 4-6 times
Intersex disorder – Klinefelter s syndrome
Testicular atrophy
Truma – prompt medical evaluation
Chromosomal abnormalities – loss of chr 11,13 &18
Abnormal chr 12p
Sex hormone fluctuations, estrogen adm during pregnancy
Carcinoma in situ (ITGCN).
Previous testicular cancer.
9. Intratubular Germ Cell Neoplasia.
With the exception of spermatocytic seminoma, all adult invasive
GCTs arise from ITGCN.
ITGCN consists of undifferentiated germ cells that have the appearance
of seminoma that are located basally within the seminiferous tubules.
The presence of ITGCN does not carry any prognostic
implications with regard to the risk of relapse of the cancer
(von Eyben et al, 2004).
ITGCN is much less frequent in pediatric GCTs(Cheville , 1999).
10. Seminoma
Seminoma is the most common type of GCT.
Seminomas occur at an older average age than NSGCTs, with most cases
diagnosed in the fourth or fifth decade of life (Rayson et al, 1998).
Grossly appearance:
Seminomas consist of a sheet like arrangement of cells.
Seminomas may be confused with solid-pattern EC, yolk sac tumor, or Sertoli cell
tumors
Seminoma arises from ITGCN and is considered to be the common precursor for
the other NSGCT subtypes
ability of seminoma to transform into NSGCT elements has important therapeutic
implications for the management of seminoma
11. Spermatocytic Seminoma
Spermatocytic seminoma is rare
and accounts for less than 1% of GCTs.
Unlike other GCTs, spermatocytic seminoma does not arise from
ITGCN.
Is not associated with a history of cryptorchidism or bilaterality.
does not occur as part of mixed GCTs.
It is a benign tumor (only one documented case having
metastasized).
and is almost always cured with orchiectomy.
12. Embryonal Carcinoma
EC is an aggressive tumor associated with a high rate of
metastasis, often in the context of normal serum tumor
markers.
EC is the most undifferentiated cell type of NSGCT.
Ability to differentiate to other NSGCT cell types
(including teratoma) within the primary tumor or at
metastatic sites.
EC has been associated with an increased risk of occult
metastases in clinical stage (CS) I NSGCT.
13. Choriocarcinoma
Choriocarcinoma is a rare and aggressive tumor that
typically presents as elevated serum hCG levels and
disseminated disease.
Choriocarcinoma commonly spreads by hematogenous
routes.
and common sites of metastases include lungs and brain, but
eye and skin metastases have also been reported (Tinkle et
al, 2001; Osada et al, 2004).
testicular choriocarcinoma is prone to hemorrhage,
sometimes both spontaneously and immediately after
chemotherapy.
14. Yolk Sac Tumor
Represent a very small fraction of adult-type GCTs.
Common in mediastinal and pediatric GCTs & Mixed
GCTs.
Hyaline globules are a characteristic feature.
Yolk sac tumors almost always produce AFP but not hCG.
Normal serum tumor markers in presence of a yolk sac tumor
is associated with a lower risk of relapse.
Serum tumor markers AFP having a higher sensitivity for
detecting micrometastatic disease in this type of GCT.
15. Teratoma
Teratomas are tumors that contain well-differentiated or incompletely differentiated
elements of at least two of the three germ cell layers of endoderm, mesoderm, and
ectoderm
Teratomas are generally associated with normal serum tumor markers, but
they may cause mildly elevated serum AFP levels.
Teratoma is resistant to chemotherapy
Teratomas may grow uncontrollably, invade surrounding structures,and
become unresectable (known as growing teratoma syndrome).
Rarly, teratoma may transform into a somatic malignancy such as
Rhabdomyosarcoma, adenocarcinoma, or primitive neuroectodermal tumor.
16. Spread of Tumour
Local
Lymphatic
Right inter aortocaval at L2 paracaval
preaortic Right common iliac Right ext.
iliac
Left Paraortic at renal hilium preaortic
common iliac Left ext. iliac
(Cross metastasis more common in right side
tumour)
17. Staging
TNM Staging of Testicular Tumor: American Joint Committee on Cancer and Union
Internationale Contre le Cancer
Primary tumor (T)
pTX: The primary tumor cannot be assessed
pT0: There is no evidence of primary tumor
pTis: Carcinoma in situ (non-invasive cancer cells)
pT1: The tumor has not spread beyond the testicle and epididymis (the tubes next to the testicles
where sperm mature). The cancer has not reached nearby blood vessels or lymph vessels. The
cancer might have grown through the inner layer surrounding the testicle (tunica albuginea), but
it has not reached the outer layer covering the testicle (tunica vaginalis).
pT2: Similar to T1 except that the cancer has spread to blood or lymph vessels near the tumor,
or the tunica vaginalis
pT3: The tumor is growing into the spermatic cord (which contains blood vessels, lymph vessels,
nerves, and the vas deferens)
pT4: The tumor is growing into the skin surrounding the testicles (scrotum)
18. Staging
Regional lymph nodes (N)
NX: Regional (nearby) lymph nodes cannot be assessed
N0: No spread to regional lymph nodes is seen on imaging tests
N1: The cancer has spread to at least one lymph node, but no lymph node is larger than 2 cm (about ¾ inch) across
N2: The cancer has spread to at least one lymph node that is larger than 2 cm but is not bigger than 5 cm (2 inches)
across
N3: The cancer has spread to at least one lymph node that is larger than 5 cm across
If the lymph nodes were taken out during surgery, there is a slightly different classification:
pNX: Regional (nearby) lymph nodes cannot be assessed
pN0: Examination of regional lymph nodes removed with surgery reveals no cancer spread
pN1: Examination of regional lymph nodes removed with surgery reveals cancer spread in 1 to 5 lymph nodes, but no
lymph node is larger than 2 cm (about ¾ inch) across
pN2: Examination of regional lymph nodes removed with surgery reveals cancer spread in at least one lymph node that
is bigger than 2 cm but not larger than 5 cm across; OR spread to more than 5 lymph nodes that aren’t bigger than 5
cm; OR the cancer is growing out the side of a lymph node
pN3: Examination of regional lymph nodes removed with surgery reveals cancer spread in at least one lymph node that
is bigger than 5 cm across
19. Staging
Distant metastasis (M)
M0: There is no distant metastasis (no spread to lymph nodes outside the area of the
tumor or other organs, such as the lungs)
M1: Distant metastasis is present
M1a: The tumor has metastasized to distant lymph nodes or to the lung
M1b: The tumor has metastasized to other organs, such as the liver, brain, or bone
20. Staging
LDH (U/liter) HCG (mIU/ml) AFP (ng/ml)
SX Marker studies not available or not done.
S0 Normal Normal Normal
S1+ <1.5 x Normal <5,000 <1,000
S2+ 1.5 - 10 x Normal 5,000 - 50,000 1,000 - 10,000
S3+ >10 x Normal >50,000 >10,000
21. Stage grouping
Stage T N M S
Stage 0 Tis (in situ) N0 M0 S0
Stage I T1-T4 N0 M0 SX
Stage IA T1 N0 M0 S0
Stage IB T2-T4 N0 M0 S0
Stage IS Any T N0 M0 S1-S3
Stage II Any T N1-N3 M0 SX
Stage IIA Any T N1 M0 S0-S1
Stage IIB Any T N2 M0 S0-S1
Stage IIC Any T N3 M0 S0-S1
Stage III Any T Any N M1 SX
Stage IIIA Any T Any N M1a S0-S1
Stage IIIB Any T N1-N3 M0 S2
Any T Any N M1a S2
Stage IIIC Any T N1-N3 M0 S3
Any T Any N M1a S3
Any T Any N M1b Any S
Once the T, N, M, and S
categories have been
determined, they are combined
in a process called stage
grouping by The AJCC and
UICC staging systems
22. Staging Imaging Studies
Clinical Staging of the Abdomen and Pelvis:
All patients with GCT should undergo staging imaging studies of the abdomen and
pelvis. Computed tomography (CT)
Retroperitoneal lymph nodes greater than 5 to 9 mm in the primary
“landing zone,” particularly if they are anterior to the great vessels on transaxial CT
images, should be viewed with suspicion for regional lymph node metastasis.
23. Postorchiectomy abdominopelvic CT scan in a
patient with right testicular NSGCT showing a 7-mm lymph node
in a primary landing zone. The lymph node was involved with
teratoma at RPLND.
24. Clinical features
A. Presentations
Gradually increasing lump / hardness in testis
Abnormal sensitivity – numbness / heaviness / Pain
Loss of sexual activity
Dull ache in lower abdomen / groin
Haemospermia
General weakness
Metastatic presentations --
25. Clinical features
Metastatic presentations (10%)
Cough and Dyspnea
Anorexia
Nausea / Vomiting (retro duodenal LN)
Neck mass
Swelling lower extremity (IVC obstruction)
Back pain (retroperitoneal L. N.)
Gynaecomastia
Bone pains
Unilateral limb swelling (L.N metastasis)
27. Diagnostic Testing and
Initial Management
Scrotal Ultrasonography
Intratesticular extratesticular pathology .
On Ultrasonography the typical GCT is hypoechoic.
Heterogeneous lesion is more commonly associated with NSGCT.
seminomas usually have a homogeneous echotexture.
The presence of increased flow within the lesion on color Doppler Ultrasonography
is suggestive of malignancy, although its absence does not exclude GCT
Both testes should be evaluated ultrasonographically.
28.
29. Serum Tumor Markers
Testicular cancer is one of the few malignancies
associated with accurate serum tumor markers
(LDH, AFP, and hCG).
Essential in its diagnosis, prognosis, treatment,
and monitoring.
Patients suspected of having a GCT should have
blood drawn for serum AFP, hCG, and LDH
evaluation before orchiectomy to aid in the
diagnosis and to help interpret postorchiectomy
tumor marker levels.
30. Serum Tumor Markers
AFP
At diagnosis, AFP levels are elevated in 50% to 70%
of low-stage (CS I, IIA, IIB) NSGCT
60% to 80% of advanced (CS IIC, III) NSGCT.
EC and yolk sac tumors secrete AFP.
Choriocarcinoma and seminomas do not produce AFP.
Patients with pure seminoma in the primary tumor with
an elevated serum AFP value are considered to have
NSGCT.
The half-life of AFP is 5 to 7day
31. Serum Tumor Markers
hCG
hCG levels are elevated in 20% to 40% of low-stage
NSGCT and 40% to 60% of advanced NSGCT.
15% of seminomas secrete hCG.
hCG is also secreted by choriocarcinoma and EC.
Levels greater than 5000 IU/L are usually associated with
NSGCT.
The half-life of hCG is 24 to 36 hours.
33. Serum Tumor Markers
LDH
LDH levels are elevated in approximately
20% of low stage GCTs and 20% to 60% of
advanced GCTs.
Lymphoma may also cause elevated LDH
levels.
main use is in the prognostic assessment of
GCT at diagnosis.
half-life of LDH is 24 hours.
34. Serum Tumor Markers
In rare patients who present with a testicular,
retroperitoneal, or mediastinal primary tumor and
whose disease burden has resulted in a need to
start treatment very urgently, substantially
elevated serum AFP and/or hCG levels may be
considered sufficient for diagnosis of GCT.
35. Radical Inguinal Orchiectomy
A radical inguinal orchiectomy with removal of the tumor-
bearing testis and spermatic cord to the level of the internal
inguinal ring.
A transscrotal orchiectomy or biopsy is contraindicated
because it leaves the inguinal portion of the spermatic
cord intact and may alter the lymphatic drainage of the
testis, increasing the risk of local recurrence and pelvic
or inguinal lymph node metastasis.
Radical orchiectomy establishes the histologic diagnosis and
primary
T stage, provides important prognostic information.
Is curative in 80% to 85% and 70% to 80% of CS I seminoma
and CS I NSGCT, respectively.
36. Radical Inguinal Orchiectomy
The external oblique fascia is
divided in line with its fibers down
to the external inguinal ring.
After the cord has been controlled
with a tightened Penrose drain or
rubber-shod clamp, the testis is
mobilized out of the scrotum using
blunt dissection.
38. Testis-Sparing Surgery
Testis-sparing surgery (or partial orchiectomy)
controversial and has no role in the patient suspected of
having a testicular neoplasm with a normal contralateral
testis.
it may be considered for organ confined tumors of less
than 2 cm in patients with synchronous bilateral tumors
or tumor in a solitary testis with sufficient testicular
androgen production.
40. Biopsy of the Contralateral Testis
biopsies of the adjacent testicular parenchyma
should be done to rule out the presence of
ITGCN.
Between 5% and 9% of patients with GCT have ITGCN in the normal
contralateral testis (Dieckmann and Skakkebaek, 1999).
In patients with an atrophic testis, history of cryptorchidism, or age
younger than 40 years, the risk of ITGCN in the contralateral testis
has been reported in up to 36% (Dieckmann and Loy, 1996).
41. Prognostic Classification of Advanced GCT
International Germ Cell Cancer Collaborative Group
The IGCCCG risk classification is used to evaluate the prognosis
of patients with metastatic GCT and the selection of chemotherapy.
For NSGCT, IGCCCG risk
Is based on the postorchiectomy serum tumor marker levels,
mediastinal primary tumor, and the presence of nonpulmonary visceral
metastases.
For seminoma, IGCCCG risk is based on the presence of nonpulmonary
visceral metastases only.
42.
43. Sperm Cryopreservation
Although infertility is an uncommon presentation for GCT, up
to 52% of men have oligospermia at diagnosis and 10% are
azoospermic.
All patients will become azoospermic after chemotherapy,
and 50% and80% of patients with normal semen
parameters at diagnosis
Will return to these levels within 2 and 5 years,
respectively (Bokemeyer et al, 1996a; Feldman et al,
2008).
Recovery of spermatogenesis after radiation therapy for
seminoma may take 2 to 3 years or more.
44. Treatment
Therapeutic Principles
After orchiectomy, staging imaging studies, serum tumor
marker status,
Chemotherapy is generally administered
regardless of low white blood cell counts or
thrombocytopenia, and nephrotoxic chemotherapy (cisplatin)
is often administered even in the presence of moderate-to-
severe renal insufficiency.
An aggressive surgical approach is taken to resect all sites of
residual disease after chemotherapy for NSGCT, even if this
involves multiple anatomic sites.
Serum tumor markers strongly influence the management of
GCTs, particularly NSGCT.
45. Contrasting Seminoma and NSGCT
Compared with NSGCT, seminoma is associated with a lower incidence of
metastatic disease and lower rates of retroperitoneal and distant
metastases.
Serum hCG is elevated in only 15% of patients with metastatic seminoma,
and serum tumor marker levels are not used to guide treatment decisions.
seminoma is sensitive to radiation therapy and platin-based chemotherapy.
radiation therapy is a standard treatment option for CS I and IIA-B seminoma
but has no role in NSGCT.
Teratoma at metastatic sites is less of a concern for seminoma compared with
NSGCT but should be considered in patients whose disease fails to respond to
conventional therapy.
46. Management of NSGCT
Clinical Stage I NSGCT:
The optimal management of these patients continues to generate controversy
because the long-term survival associated with surveillance, RPLND, and primary
chemotherapy approaches 100%.
The most commonly identified risk factors for occult metastasis are LVI and a
predominant component of EC.
The reported rate of occult metastasis (based on observed relapses on
surveillance or lymph node metastasis at RPLND) with LVI and EC predominance
varies from 45% to 90% and 30% to 80%, respectively
47. Surveillance:
The rationale for surveillance is based on the fact that
70% to 80% of patients with CS I NSGCT are cured by
orchiectomy alone and the ability to salvage all
relapsing patients with chemotherapy based on the
long-term cure rates achieved for chemotherapy for
good-risk metastatic NSGCT.
48. Retroperitoneal Lymph Node Dissection
high cure rates after RPLND alone for patients with low-
volume (pN1)
retroperitoneal malignancy and teratoma (pN1-3).
chemotherapy is restricted to those with extensive
retroperitoneal malignancy (pN2-3).
high salvage rate of relapses with good-risk, induction
chemotherapy.
Prevention of low short- and long term morbidity when a nerve-
sparing RPLND is performed by experienced surgeons.
49. Retroperitoneal Lymph Node Dissection
The long-term cancer-specific survival with RPLND (±
adjuvant chemotherapy) approaches 100%, and the risk of
late relapse is negligible.
full, bilateral template dissection is associated with the lowest
risk of abdominopelvic recurrence (<2%) and the highest rate
of antegrade ejaculation (>90%) when nerve-sparing
techniques are employed
50. Anatomic regions of the retroperitoneum
Paracaval
Precaval
Interaortocaval
Preaortic
Para-aortic
Right suprahilar
Left suprahilar
Right iliac
Left iliac
Interiliac
Right gonadal vein
Left gonadal vein
52. Surgical Technique of RPLND
Transabdominal Approach
Incision of the posterior parietal
peritoneum.
The incision extends from the
ligament of Treitz along the left side
of the root of the small bowel
mesentery to the ileocecal region
It may be extended superiorly and
medially to the duodenojejunal
flexure and inferolaterally around the
cecum and ascending colon.
The left leaf of the incised posterior
peritoneum is defined…….
53. Development of the left leaf of the
incised posterior peritoneum
the avascular plane between the
inferior mesenteric vein (IMV)
and the left gonadal vein.
The colonic mesentery lies anteriorly
and the para-aortic space and Gerota
fascia posteriorly. SMA, superior
mesenteric artery; LRV, left renal vein.
54. The retroperitoneal space has been
exposed.
Duodenum reflected superiorly along
with the pancreas and superior
mesenteric artery.
The entire right colon has been
mobilized up.
55. This diagram sequentially shows the “split and roll” technique
The lumbar vessels must be divided twice,
56. Nerve-Sparing Techniques
vascular tapes around the right
postganglionic branches of the
sympathetic chains.
they course in an oblique fashion
toward the hypogastric plexus.
57. Primary Chemotherapy
adjuvant chemotherapy given for pathologic stage II disease after RPLND.
The goal of primary chemotherapy is to minimize the risk of relapse.
The disadvantages of primary chemotherapy are:
(1) it does not treat retroperitoneal teratoma and thus exposes patients to the
potential for chemoresistant and/or late relapse.
(2)long-term surveillance CT of the retroperitoneum is required.
(3) all patients are exposed to chemotherapy and the potential risk of late toxicity.
58. Clinical Stage IS NSGCT
CS IS is defined as the presence of elevated Postorchiectomy
serum tumor markers without clinical or radiographic evidence
of metastatic disease.
Studies of primary RPLND for CS IS NSGCT have reported
that 37% to 100% of patients subsequently required
chemotherapy for retroperitoneal metastasis, persistently
elevated serum tumor markers, or relapse
59. Clinical Stage IIA and IIB NSGCT
RPLND (± adjuvant chemotherapy) and induction chemotherapy (±
postchemotherapy RPLND) are accepted treatment options, with survival rates
exceeding 95%.
the risk of occult systemic disease, risk of retroperitoneal teratoma, short- and
long-term treatment-related morbidity, and need for double therapy.
CS IIA-B NSGCT patients with elevated AFP or hCG or bulky lymph nodes (>3 cm)
should receive induction chemotherapy.
60. Clinical Stage IIC and III NSGCT
Induction chemotherapy with cisplatin-based multiagent regimens is the initial
approach used for the treatment of CS IIC and CS III NSGCT
The specific regimen and number of cycles is based on the IGCCCG risk
stratification.
Chemotherapy for Good-Risk NSGCT:
For patients at good risk, two randomized trials have shown that BEP×3 is not
inferior to BEP×4.
Chemotherapy for Intermediate- and Poor-Risk NSGCT:
BEP×4 remains the standard first-line regimen in patients with intermediate- and
poor-risk disease.
62. Chemotherapy-Naive NSGCT Relapse.
relapses occur in men with CS I NSGCT managed with either
surveillance or RPLND and in the men with CS IIA-B NSGCT
treated with RPLND alone.
In general these patients are treated with induction
chemotherapy, with the specific regimen and duration of
therapy determined by IGCCCG risk, and cure rates exceed
95%. Select CS I NSGCT patients on surveillance who
experience relapse in the retroperitoneum with nonbulky (<3
cm) disease and normal serum tumor markers may be treated
by induction chemotherapy or RPLND (particularly if teratoma
was present in the primary tumor)
63.
64.
65. Management of Seminoma
Clinical Stage I Seminoma:
primary radiotherapy, and primary chemotherapy with single-
agent carboplatin are now accepted treatment options.
Platin-based chemotherapy and infradiaphragmatic
radiotherapy are associated with an increased risk of late
cardiovascular toxicity and secondary malignant neoplasms.
The long-term cancer control with each of these modalities
approaches 100%.
66. Primary Radiotherapy:
The optimal radiation dose has not been defined, and most
centers use 25 to 35 Gy in 15 to 20 daily fractions
In-field recurrence after dog-leg radiotherapy is less than 1%.
The most common sites of recurrence are the thorax and left
supraclavicular fossa. Virtually all recurrences are cured with
first-line chemotherapy.
risk of developing secondary malignant neoplasms is estimated
to be 18% at 25 years after radiotherapy for seminoma.
68. Surveillance in seminoma
Compared with NSGCT, surveillance for CS
I seminoma is complicated by the limited of
serum tumor markers to detect relapse and
the need for long-term surveillance CT
because 10% to 20% of relapses occur 4
years or more after diagnosis.
69. Primary Chemotherapy with Single-Agent
Primary chemotherapy with one to two cycles of
single-agent carboplatin
Carboplatin dosing should not be based on
estimated GFR. Thus, it is recommended to base
one cycle of carboplatin dosing on the results of
radioisotope renal scans or administer two
cycles of therapy.
70. Clinical Stage IIA and IIB Seminoma.
20 % of seminoma patients have CS II disease, 70% of whom
have
CS IIA-B. Dog-leg radiotherapy using 25 to 30 Gy is employed
at most centers.
Induction chemotherapy is preferentially given to patients with
bulky
(>3 cm) and/or multiple retroperitoneal masses because the risk
of relapse is lower than with dog-leg radiotherapy.
71. Clinical Stage IIC and III Seminoma
Patients with CS IIC and III seminoma are treated with
induction chemotherapy, with the regimen and number of
cycles determined by the IGCCCG risk. 90% percent of
patients with advanced seminoma are classified as good risk
and should receive either BEP×3 or EP×4 chemotherapy.
Management of Postchemotherapy Residual Masses:
Spontaneous resolution of these masses is reported in 50%
to 60% of cases.
72. Postchemotherapy Seminoma Relapse
An estimated 15% to 20% of patients with advanced
seminoma will experience relapse after induction
chemotherapy.
for patients with advanced seminoma who experience relapse
after first-line chemotherapy is the potential for teratoma at
the site of relapse. Thus patients with normal values of serum
tumor markers should undergo biopsy before starting second-
line chemotherapy.
Late Relapse:
late relapse of seminoma may have a favorable prognosis,
particularly among patients without prior exposure to cisplatin
73. Brain Metastases
Brain metastases are associated with choriocarcinoma and
should be suspected in any patient with a very high serum
hCG level.
Choriocarcinomas are highly vascular and tend to
hemorrhage during chemotherapy, and death rates of 4% to
10% due to intracranial hemorrhage have been reported.
Patients with brain metastases at diagnosis should receive
BEP×4 chemotherapy followed by resection of residual
masses.
