Seminar : Germ Cell Tumour In Males

Presenter : Dr. Musaib Mushtaq

MODERATOR : Dr. Arshad Manzoor

Dated : 09-Nov-2021
Anatomy
 4x3x2.5cc
 Acquires coverings during
descent from genital ridge to
scrotum
 Coverings-tunica albuginia,
tunica vaginalis, internal
spermatic facia, cremastric
fascia, external spermatic
fascia, scrotum(skin &
dartos)
 250-400 lobules converge at
mediastinum-12-20 efferent
ducts-epididymis
Lymphatic drainage
4-8 lymphatic trunks drain hilum of the testis, and run along
spermatic cord up to the internal inguinal ring.
Drain into retroperitoneal LNs between T11-L4, with majority
between L1-L3
Then upward via thoracic duct through mediastinum and to
supraclavicular fossae, and occasionally to axillary LNs

 Right testis tumor  Left testis tumor

Landing zone: Inter-aorto- Landing zone: Para-aortic

caval LNs immediately
below renal vessels
Ipsilateral distribution:
para-caval, pre-aortic,
right common iliac
Para-aortic LNs are
considered contra-lateral
LNs below left renal vessel
Ipsilateral distribution:
para-aortic, pre-aortic, left
common iliac
Para-caval LNs are
considered contra-lateral
Classification of GCT
 CIS/TIN
CARCINOMA IN SITU / TESTICULAR
INTRAEPITHELIAL NEOPLASIA

 Precursor of all GCT except spermatocytic seminoma.

 Found adjacent to 100% cases of all GCT except SS
 Diagnosis by biopsy, routine screening not recommended, other
than high risk-presumed extragonadal GCT.
 Rx controversial, 100 % lead to GCT.
 Orchidectomy - u/l
 Low dose RT 16-20 gy – b/l
Testicular biopsy

 Role of FNAC and biopsy limited only if extratesticular

disease is suspected. Role in testicular mass is for
contralateral testis showing atrophy- vol<12ml.
 In a obvious case of tumor, it is a condemed procedure.
Introduction
 Testicular tumors are rare, 1-2% of adult male solid tumors.
 Most common testicular tumors are Germ Cell Tumors.
(>90%)
 Different classifications of GCT, clinically broadly classified
as-
 Pure Seminomas.
 Non Seminomous Germ Cell Tumors including
Embryonal ca, Yolk sac tumor, Teratoma, Choricarcinoma,
Mixed GCT.

 Seminomas are most common type of GCT. (40-45%)

 Age of presentation- 4TH decade of life.
 Usually diagnosed at early stage.
Etiology
 Infertility and semen quality-
 Impaired maternal hormones
 Low semen conc., poor semen mobility, abnormal sperms.

 Testicular maldescent- cryptorchidism

 Seminoma > NSGCT
 More common with intra abdominal testis
 Factors- increased temp, increased trauma
 Contra lateral - 5-20%. Suggest some prenatal etiological process.
 Other genitourinary abnormalities associated- hydrocele,
hypospadias.

 Immunosuppression – HIV/organ transplant.- 3rd m/c tumor.

 Prior testicular tumor.
 Familial history.
 Inguinal hernia before age 15yrs
Linked factors
Mumps orchitis
Testicular trauma
Nutrition and greater limb length.
Prenatal causes :- increased maternal unbound
estrogen- threatened miscarriage, excessive
maternal nausea vomiting, delivery by caesarian.
Late puberty - protective effect.
Genetics
 Seminomas – triploid,
tetraploid;

 Anomaly of all GCT-

isochromosome of chr12
short arm or extra copies
of 12p segments
incorporated in other
chromosomes.

 P53, bcl2, mdm, c-kit, K-

ras gene,

 N- myc gene.
 Clinical Evaluation
 History– cryptorchidism,
previous inguinal or scrotal
surgery, h/o trauma, family h/o.
 Clinical features on
examination-
• Painless Testicular mass
(MC)
• Pain, a/c epididmytis 10%.
• Heaviness, tenderness, vague
abd dragging pain- 38%
• Hydrocele, trauma
• Systemic disease signs- back
pain, abd swelling,
dyspnoea, gynecomastia.
Contralat testis exam should be never missed.

GCT should be considered as a potential aetiology for a

retroperitoneal mass in all male patients regardless of age.
 Diagnostic work-up!
USG Testis: 7.5 Hz- 100% sensitivity
Laboratory tests-
Complete blood counts
KFT+LFT including LDH
Serum markers- B-HGG, AFP, PLAP before
and after SX.
Pulmonary fn tests
Sperm analysis and sperm banking should be
always considered and discussed with patient.
Tumor markers
T T 1/2 N value Comments
Marker
B- 2-22hrs <5 IU/L -15% seminoma
HCG -correlates tumor mass so
prognostic value
LDH 1day 105 - 333 -poor specificity
IU/L -Not diagnostic
-prognostic marker
-correlates tumor burden
PLAP 1 day -90% histology +ve
- serum levels are elevated
in 50 to 72% of higher
stage.
AFP 5Days 20ng/ml Raised levels exclude
seminoma
Radiological studies
CXR – PA view all pts.
CT chest – stage II seminomas.
G Horan 182 pts -in stage I disease, where
abdominal CT and chest x-ray are normal, staging
CT chest gives a false-positive rate of 100%.

CT abdomen pelvis-

 Investigation of choice for RPLN,
 >1 cm node +ve.
 Secificity-94%, sensitivity- 50-70%.
 15-20% have radiological evidence of RPLN.
MRI – no added adv.

Bipedal lymphangiography-
 Invasive, Obsolete
Don’t add diagnostic accuracy.

PET-
 no added advantage in primary evaluation
 Unable to detect <5mm LN
 role in eval residual d/s after Rx under investigation.

Bone scan.
FNAC/Bx.
Radical Orchiectomy
Performed as a rule prior to any other treatment as it
is Diagnostic and therapeutic.
Inguinal incision, tumor bearing testis removed with
spermatic cord at the level of internal inguinal ring.

Removes primary tumor

Confirms histological diagnosis.
Tells about prognostic factors- tumor size/rete
testis invasion/ LVI.

Further Mx on basis of histology, stage,

prognostic factors.
Royal Marsden Hospital staging
 I - No evidence of metastases
beyond testis. •IV - Extralymphatic
metastases
 IM- Rising serum markers with
no other evidence of metastases. Lung
L1 </=3
 II - metastases
Abdominal node metastases
 A <2 cm in diameter L2>3 metastases all
 B 2–5 cm in diameter < 2 cm in diameter
 C >5 cm in diameter L3>3 metastases,
one or more > 2 cm
 III - Supradiaphragmatic node
in diameter
metastases
 M-Mediastinal H +Liver metastases
 N-Supraclavicular cervical Br +Brain metastases
axillary Bo +Bone metastases
 O-No abdominal node
metastases
 ABC- Node size defined as in
Stage II
 STAGE WISE
TREATMENT OPTIONS
AND
THEIR DISCUSSION.
TREATMENT MODALITIES
 High inguinal orchidectomy
 Radiotherapy
 Chemotherapy
 Surveillance – stage I
 Sperm testing and banking should be considered before
treatment with CT/RT/RPLND.
RADIOTHERAPY PRINCIPLE-
 Highly sensitive tumor, even 20 Gy may be curative.

 Predictable nodal spread, so treat next station of lymph

nodes, where there is high chance of recurrence.
 Rate of infield recurrence very low- 0.2%

 Tried and tested technique since ages.

Radiotherapy indications-
 Stage I – Rx of choice
 Stage II A, IIB – Rx of choice
 Stage II C/III- pre CCT/post CCT/historical
 Salvage treatment.
RADIOTHERAPY TECHNIQUE-
Different fields depending on stage

 Dog Leg Field – stage I, IIB

 Para-aortic Field alone - stage I
 L –field – stage II B
 Modified field - stage IIB/C
 Inverted T shaped field – stage II B/C
 Whole abdominal RT- stage IIC/III historical.
 Prophylactic mediastinal & SCLN RT- stage II C –
historical.
 Locoregional RT - relapse
 Chemotherapy  BEP- 3 wkly X 3/4
cycles
 Principle- Bleomycin+Etoposi
 Highly chemo sensitive de+Cisplatin
 Less toxic options in early stage.  VIP x 3 wkly
 Treatment of choice in wide spread Etoposide+Ifosfamid
disease. e+Cisplatin +Mesna
 TIP
 Indications- Paclitaxel+Ifosamid
 Stage I- single agent carboplatin. e+Cisplatin
 Stage II A & B – pre RT single cycle  EP- 3wkly X 4
carboplatin, not recommended cycles
 Stage II C - alternative to RT/pre RT Etoposide+Cisplatin
chemotherapy  PVB x 3 wkly, 4
 Stage III- treatment of choice.
cycles
 Relapse - treatment of choice
 Any stage- contraindication for RT- Cisplatin+Vinblastin
inflam bowel disease, prev RT, horse e+Bleomycin
shoe kidney , pelvic kidney.
 Stage I
 70-80%.

 Crossover drainage from right to left occurs routinely

but left to right nodal drainage occurs in only 15% to
25% of cases.
 20% stage I harbor micro mets in RPLN.

 Pelvic lymph node involvement is present in 1% to 3%

of cases.
 Inguinal lymph node involvement is even rarer and
limited to factors leading to altered lymphatic drainage
of the testis -very extensive local disease, incomplete
surgery, and gross scrotal contamination prior to
surgery.
Treatment options-
 RADIOTHERAPY- Rx of choice
 SURVEILLANCE
 CHEMOTHERAPY

Radiotherapy
 Highly sensitive - Very low dose – 20Gy-30Gy is curative
 Predictable sequential nodal spread.
 Rate of infield recurrence very low- 0.2%
 After RT, RFS- 97% & DFS- >99%.
 Thus, Treatment of choice

Radiotherapy options-
 Dog Leg Field,
 Para Aortic field
Dog Leg Field or
Hockey stick Field
Traditionally called hockey stick in N. America &
dog leg in Europe.

Target volume –
interaortocaval, preaortic, and para-aortic nodes,
left renal hilar nodes are included for left-sided
tumours,
ipsilateral external iliac and common iliac nodes
included if there is concern about aberrant drainage.
Inclusion of the inguinal scar, inguinal lymph
nodes, or hemiscrotum is not warranted in the
routine treatment of stage I disease.
Dog leg
 Position- supine
 IVP/CT to identify kidney
 Boundaries-
 Superior border- T9-T10 or
T10-11.
 Inferior border –up to
inguinal ligament or at top of
obturator foramen or may be
raised to above the acetabulum.
 Lateral border – Para aortic
field at transverse process of
vertebra, with width=10-12
cm,except at renal hilum
 At the mid-L4 level field is
extended laterally to cover
ipsilateral ELN.
 AP/PA parallel opposed fields.
•Left sided tumour - lateral border
extended to include the left renal
hilum,

•Penis is moved out of field.

•C/L Testis shielded to preserve

fertility and hormonal function.

•Individualized CT-based planning

Multileaf collimators replacing lead
blocks

Traditional field placement based

on bony anatomy provides
adequate coverage of the nodal
CTV for most patients.
Dose
 Minimum dose to control occult seminoma not defined. Dose
of 25-30 Gy appears adequate.

 Radiation doses of less than 20 Gy have been associated with

in-field failures.> 40 Gy has been found to be unnecessary

 MRC TE18 trial - 20Gy/10# vs. 30Gy/15#, 625 pts-

 No significant diff. in relapse pattern at 60m,
 20Gy- less a/c toxicity, returned to work early,
 Need long follow up.

 Hypofractionated schedules of 20Gy/8# have been used with

no in-field reccurence, ORR-3.5% but 42% increased in GI
toxicity.
Complications
1> acute toxicity-
MC- GI-(60% in dog leg field)- mild nausea, vomiting, diarrhea
most common. Peptic ulcer, obstruction, h’agic gastritis rare in
current doses-
 <25gy-0%
 23-35gy-2%
 35-45gy-6%

2> late gonadal toxicity-

- scatter dose
- temporary azospermia, 2Gy –permanent injury.
- Shielding recommended.

3>Second primary-
Sarcomas, Ca Pancreas, Ca Bladder
ALL, nonlymphocytic leukemia, NHL both CCT and RT.
Contra lateral Testicular dose and shielding
Unavoidable dose to testis due to int. scatter
50% impaired spermatogenesis at presentation, with 40%
azospermic.
RT further impairs dose dependent fashion, permanent
injury at 2Gy.
 EXTERNAL SHIELDING
Retraction -40%
11mm thick lead shield-50%
Clamshell technique 1-2% dose.
 No shielding if scrotal orchidectomy done
 INTERNAL SHIELDING
Tungsten 0.5 mm.
Kept between Dartos and External spermatic fascia.
Invasive + cumbersome procedure.
RT results DL Stage I
 OSS 92-99% at 5-10yrs
 CSS cause-specific survival- 100%
 Relapse rate – 0.5-5%
PROGNOSTIC
 Infield relapse is rare-<0.2%
 Most common sites of relapse
FACTORS
are pelvic nodes if not in field,
mediastinum, lungs, L. Involvement of
SCLN. T albuginea,
 Uncommon relapses - inguinal Epididymis,
Spermatic cord.
nodes due to predisposing
LVI
factors, brain, tonsil.
Pre op B-HCG
 Supra diaphramatic relapses
Chemo is the treatment, while
inguinal nodes RT.
SIMPLE PARA AORTIC FIELD
 Rationale-
 Predominant nodal drainage is to
Para aortic and renal hilar nodes.
 Pelvic relapses – 1.7 %, easily
salvageable.
 Reduction in acute GI toxicity &
chronic GI toxicity.
 Risk of 2nd malignancy in target
volume.
 Dose to c/l testis reduced <2 Gy, so no
shield req.
 Faster recovery of sperm count.
 FIELD - similar to Para aortic field of dog
leg field, i.e. – T10/11 to lower border of
L5. AP/PA parallel opposed fields.
 DOSE- same as DL feild
 Conclusion – stage I
100% pts cured regardless of post Sx Rx.

RT : Rx of choice.

Surveillance is an attractive option & can be applied

in careful and limited clinical settings only, where it
doesn’t compromise survival & cost is taken care.

Less toxic alternative to RT- single agent

Carboplatin 1-2 cycles 400mg/m2 ( 7 AUC) is equally
potential modality as RT for stage I d/s.
Stage II
 15-20% of seminoma.
 70% of stage II are II A/B.
 Three groups depending on diameter of PA-LN (most imp prognostic
indicator) defined by largest LN mass on CT.
 IIA-<2cm OSR- 96-100%
 IIB-2.1-5cm OSR- 96-100%
 IIC->5cm OSR>90%
 Relapse is most commonly in mediastinum, supraclavicular fossa and lung.

 Rx Options-
 RADIOTHERAPY- Rx of choice in IIA/B
- historical in II C
 CHEMOTHERAPY -experimental in stage II A/B
-Rx of choice in II C
 RT-Stage-II A
Target volume- Para-aortic and ipsilateral pelvic lymph
nodes.
RT Techniques in stage IIA
 DOG LEG FIELD
 L- SHAPED FIELD
 Borders – superior- T10/11
 Laterally covering up to transverse process of spine.
 Inf - till L5/S1
 Trace the ipsilateral pelvic brim, opposite side 2-3 cm from lat
border of Para aortic lat field
 Inf. border- lower border of obturator foramen.
Same dose as used in stage I
 Modified Field II B
 TARGET VOLUME CHANGES TO ENCOMPASS THE
ENLARGED NODES WITH MARGINS.

 TECHNIQUES-
 Widened Dog Leg Field / L Shaped field to encompass the
LN as seen on CT with margins of 2 cm.

 Inverted T – Shaped field

 To irradiate the c/l pelvic nodes
 In bulky disease , retrograde spread.
 Central pelvic shield can be used.

Dose- total 35 gray,

 initial dose – 25 gray/20#
 followed by field reduction to enlarged nodes with 2
cm margin – 10 gray/5-8#.
RT-IIC
 TARGET –
 Same principle as stage II B, abdominal
fields are larger to cover the disease.
 also due to large disease in abd next station
i.e. mediastinum is also at risk. 30%
 Historically given as whole abdominal RT
with prophylactic mediastinal RT.
 Total abdominal radiation to 15 Gy
 Kidney blocks are placed for additional 10
Gy.
 The para-aortic region and the ipsilateral iliac
region given additional 10 Gy:
 Mediastinum and SCLN – 25 Gy.
 The total dose to the iliac and para-aortic
region = 35Gy.
 The total dose to the rest of the abdomen is
25 Gy.
Total Nodal Irradiation- historical

Included additional B/L iliac

lymph node regions (common

plus external iliac) and/or the
homolateral hemiscrotum to
prevent recurrence after altered
lymphatics due to previous
hernioraphy or scrotal violation.
Chemotherapy in II A/B and IIC
Indications-

A single course of Carboplatin 400 mg/m2 4-6 wks

prior to RT cannot be used as routine in Stage II A/B.
Stage II C
 Tumor bulk- extending 10 cm with multiple enlarged
lymph nodes from L1-5 with max transverse dia - 4 cm.
 Location of disease- more laterally risking kidney/liver

 IIC- Chemo is considered treatment of choice.

 Results- progression free survival- 90%
 BEP- 3 cycles
 EP- 4 cycles
 Stage III
 5% of total seminoma

 Historically – total nodal RT and whole abdominal RT with

mediastinal RT were used, with modifications to cover
disease.

Chemotherapy is the treatment of choice.

 Earlier PVB regime was used.
 Currently BEP/EP have replaced PVB regime due to less
toxicity maintaining equal efficacy.
Residual RPLN mass
 Residual mass post RT, Chemo in Stage IIC and III is common
and Rx of this is controversial.
 Possibility of NSGCT component, so biopsy/FNAC and serum
markers always recommended.
 Options- Observation/surgical/Chemo/RT
 Stable mass is usually fibrosis/necrosis with minority only active
d/s. so observation can be relied here
 Surgery technically difficult and highly morbid.
 Relapse and Failure

 Unfavorable relapse – either same Chemo regimes as for

favorable group/ high dose Chemo with best supportive care
under trial can be tried.

 On failure, Palliative Chemo with supportive care is

recommended. GEMOX

 In refractory metastatic disease localised to a area

localised palliative RT/ Sx may be used.
Extragonadal GCT
 Similar histology as GCT, but found elsewhere in absence of a
testicular mass.
 1-5% of GCT.
 Age of presentation in young men is 5-10 yrs older than
testicular GCT
 Infants EG-GCT > testicular GCT
 Worse prognosis
 Isochromosome 12p, klinefelter’s syndome
 Some pts have, Poorly differentiated, midline location, similar
cytogenetic, poor response to CCT.
 Site- midline(MC)- mediastinum, pineal & suprasellar,
sacrococcyx. Rarely – orbit, prostate, liver.
 SEMINOMA

STAGE I STAGE II C

STAGE II A/B
STAGE III

RT
Chemo
RT