Oncology

1. Presenter : Dr. Musaib Mushtaq
MODERATOR : Dr. Arshad Manzoor
Dated : 09-Nov-2021
Seminar : Germ Cell Tumour In
Males

2. 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

3. 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
 Landing zone: Inter-
aorto-caval LNs
immediately below renal
vessels
 Ipsilateral distribution:
para-caval, pre-aortic,
right common iliac
 Para-aortic LNs are
considered contra-
 Left testis tumor
 Landing zone: Para-
aortic LNs below left
renal vessel
 Ipsilateral distribution:
para-aortic, pre-aortic,
left common iliac
 Para-caval LNs are
considered contra-
lateral

4. Classification of GCT

5. 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

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. Tumor markers
T
Marker
T 1/2 N value Comments
B-
HCG
2-22hrs <5 IU/L -15% seminoma
-correlates tumor mass so
prognostic value
LDH 1day 105 - 333
IU/L
-poor specificity
-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

14. 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

15.  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.

16. 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.

17. Royal Marsden Hospital staging
 I - No evidence of
metastases beyond testis.
 IM- Rising serum markers
with no other evidence of
metastases.
 II - Abdominal node
metastases
 A <2 cm in diameter
 B 2–5 cm in diameter
 C >5 cm in diameter
 III - Supradiaphragmatic
node metastases
 M-Mediastinal
 N-Supraclavicular cervical
axillary
 O-No abdominal node
metastases
 ABC- Node size defined
•IV - Extralymphatic
metastases
Lung
L1 </=3
metastases
L2>3 metastases all
< 2 cm in diameter
L3>3 metastases,
one or more > 2 cm
in diameter
H +Liver metastases
Br +Brain metastases
Bo +Bone metastases

18. STAGE WISE
TREATMENT OPTIONS
AND
THEIR DISCUSSION.

19. TREATMENT MODALITIES
 High inguinal orchidectomy
 Radiotherapy
 Chemotherapy
 Surveillance – stage I
 Sperm testing and banking should be considered before
treatment with CT/RT/RPLND.

20.  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.

21. 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

22. Chemotherapy
 Principle-
 Highly chemo sensitive
 Less toxic options in early
stage.
 Treatment of choice in wide
spread disease.
 Indications-
 Stage I- single agent
carboplatin.
 Stage II A & B – pre RT single
cycle carboplatin, not
recommended
 Stage II C - alternative to
RT/pre RT chemotherapy
 Stage III- treatment of choice.
 Relapse - treatment of choice
 BEP- 3 wkly X
3/4 cycles
Bleomycin+Etop
oside+Cisplatin
 VIP x 3 wkly
Etoposide+Ifosfa
mide+Cisplatin
+Mesna
 TIP
Paclitaxel+Ifosa
mide+Cisplatin
 EP- 3wkly X 4
cycles
Etoposide+Cispl
atin
 PVB x 3 wkly, 4
cycles
Cisplatin+Vinblas

23.  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.
Stage I

24.  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

25. 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

26. 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

27. •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.

28. 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.

29. 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.

30. 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.

31. RT results DL Stage I
 OSS 92-99% at 5-10yrs
 CSS cause-specific survival-
100%
 Relapse rate – 0.5-5%
 Infield relapse is rare-<0.2%
 Most common sites of
relapse are pelvic nodes if
not in field, mediastinum,
lungs, L. SCLN.
 Uncommon relapses -
inguinal nodes due to
predisposing factors,
brain, tonsil.
 Supra diaphramatic
relapses Chemo is the
treatment, while inguinal
PROGNOSTIC
FACTORS
Involvement of
T albuginea,
Epididymis,
Spermatic cord.
LVI
Pre op B-HCG

32. 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.

33. 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.

34. 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

35. 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

36. 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#.

37. 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-

38. 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

39. 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%

40. 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.

41. 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.

42.  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.

43. 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.

44. SEMINOMA
STAGE I
STAGE II A/B
STAGE II C
STAGE III
RT
RT
Chemo