This document provides information on testicular cancer, including its incidence, histology, lymph node drainage patterns, staging classifications, workup, and management guidelines. Some key points: - Testicular cancers constitute 1% of all cancers and germ cell tumors are the most common solid tumors in men aged 15-35. - Lymph node drainage patterns differ for right and left testes, with retroperitoneal lymph nodes being the most common site of spread. - Germ cell tumors are the most common type and are classified based on their histologic components. - Staging involves the TNM classification and serum tumor marker levels. Workup includes imaging, tumor marker tests, and radical orchi

1. Testicular Cancer
Dr. AADITYA PRAKASH
DNB Resident, Radiation Oncology
BMCHRC, Jaipur

2. INTRODUCTION
 Testicular cancers constitute 1% of all cancers.
 GCTs are the most common solid tumors in men between the ages of
15 and 35 years.
 In a man age 50 or older, a solid testicular mass is usually a
lymphoma.
 Approximately 90 % of GCTs originate in the testis, and 10 % are
extragonadal.
 Most curable solid neoplasm.

3. LYMPHATICS
• Right testis: along the IVC inter-aortocaval
region  pre-aortic &
para-aortic lymph nodes, with
possible cross-over within the
retroperitoneum
• Left testis: Preaortic and para-aortic
lymph nodes around the left
renal hilum  inter-aortocaval nodes
mostly without cross-over
• Retroperitoneal lymph nodes are
located anterior to the T11 to L4
vertebral bodies concentrated at the
L1–L3 level
• Nodal spread to iliac chain is
ipsilaterally but infrequent (~3%)
• Scrotal skin: lymphatics drain into the
inguinal and external iliac nodes.

4. HISTOLOGIC CLASSIFICATION OF TESTIS TUMORS
Germ cell tumors (demonstrating one or
more of the following components)
• Seminoma
• Embryonal carcinoma
• Teratoma
• Choriocarcinoma
• Yolk sac tumor (endodermal sinus tumor:
embryonal adenocarcinoma of the
prepubertal testis)
Sex cord stromal tumors (gonadal
stromal tumors)
• • Leydig cell tumor
• • Sertoli cell tumor
• • Granulosa cell tumor (adult and juvenile
types)
Tumor with both germ cell and gonadal
stromal elements
• Gonadoblastoma
Adnexal and para-testicular tumors
• • Mesothelioma
• • Tumors of soft tissue origin (e.g.,
sarcomas)
• • Adnexal tumor (e.g., adenocarcinoma)
of the rete testis
Miscellaneous neoplasms
• • Carcinoid
• • Lymphoma
• • Cyst
Metastatic neoplasms

5. CLASSIFICATIONS OF GERM CELL TUMORS

6. STAGING OF TESTIS TUMORS BY THE AMERICAN
JOINT COMMITTEE ON CANCER (AJCC)
• Primary Tumor
• The extent of primary tumor is
classified after radical orchiectomy
• pTX Primary tumor cannot be
assessed. (If no radical orchiectomy
has been performed, TX is used.)
• pT0 No evidence of primary tumor
(e.g., histologic scar in testis)
• pTis Intratubular germ cell
neoplasia (carcinoma in situ)
• pT1Tumor limited to the testis and
epididymis without
vascular/lymphatic invasion. Tumor
may invade into the tunica albuginea
but not the tunica vaginalis.
• pT2Tumor limited to the testis and
epididymis with vascular/lymphatic
invasion, or tumor extending through
the tunica albuginea with involvement
of the tunica vaginalis
• pT3Tumor invades the spermatic
cord with or without
vascular/lymphatic invasion
• pT4Tumor invades the scrotum with
or without vascular/lymphatic
invasion

7. STAGING OF TESTIS TUMORS BY THE AMERICAN
JOINT COMMITTEE ON CANCER (AJCC)
• Regional Lymph Nodes (N) Clinical
• NX Regional lymph nodes cannot be
assessed
• N0No regional lymph node metastasis
• N1Metastasis with a lymph node mass 2
cm or less in greatest dimension; or multiple
lymph nodes, none more than 2 cm in
greatest dimension
• N2Metastasis with a lymph node mass,
more than 2 cm but not more than 5 cm in
greatest dimension; or multiple lymph nodes,
any one mass greater than 2 cm but not more
than 5 cm in greatest dimension
• N3Metastasis with a lymph node mass
more than 5 cm in greatest dimension
• Pathologic Lymph Nodes (pN)
• pNX Regional lymph nodes cannot be
assessed
• pN0No regional lymph node metastasis
• pN1Metastasis with a lymph node
mass 2 cm or less in greatest dimension
and five or fewer nodes positive, none
more than 2 cm in greatest dimension
• pN2Metastasis with a lymph node
mass more than 2 cm but not more than
5 cm in greatest dimension; or more than
five nodes positive, none more than 5 cm;
or evidence of extranodal extension of
tumor
• pN3Metastasis with a lymph node
mass more than 5 cm in greatest
dimension

8. STAGING OF TESTIS TUMORS BY THE AMERICAN
JOINT COMMITTEE ON CANCER (AJCC)
• Distant Metastasis (M)
• MX Distant metastasis cannot be assessed
• M0 No distant metastasis
• M1 Distant metastasis
• M1a Nonregional nodal or pulmonary
metastasis
• M1b Nonpulmonary visceral metastasis
• Serum Tumor Markers (S)
• SXMarker studies not available or not performed
• S0Marker study levels within normal limits
• S1LDH <1.5 × N and
HCG (mIU/mL) <5000 and
AFP (ng/mL) <1000
• S2 LDH 1.5-10 × N or
HCG (mIU/mL) 5000-50,000 or
AFP (ng/mL) 1000-10,000
• S3 LDH >10 × N or
HCG (mIU/mL) >50,000 or
AFP (ng/mL) >10,000
• N indicates the upper limit of normal for the LDH
assay

9. STAGE GROUPING
• Stage 0 pTis N0 M0 S0
• Stage I pT1-4 N0 M0 SX
• Stage IA pT1 N0 M0 S0
• Stage IB pT2 N0 M0 S0
pT3 N0 M0 S0
pT4 N0 M0 S0
• Stage IS Any T N0 M0 S1-3
• Stage II Any T N1-3 M0 SX
• Stage IIA Any T N1 M0 S0
Any T N1 M0 S1
• Stage IIB Any T N2 M0 S0
Any T N2 M0 S1
• Stage IIC Any T N3 M0 S0
Any T N3 M0 S1
• Stage III Any T Any N M1 SX
• Stage IIIA Any T Any N M1a S0
Any T Any N M1a S1
• Stage IIIB Any T N1 M0 S2
Any T Any N M1a S2
• Stage IIIC Any T N1-3 M0 S3
Any T Any N M1a S3
Any T Any N M1B Any S

10. STAGING WORK UP
• General
History (document cryptorchidism and
previous inguinal or scrotal surgery)
Physical examination
• Laboratory Studies
CBC, LFT, RFT
• Serum assays
Alpha fetoprotein (AFP)
Beta human chorionic gonadotropin
LDH
• Diagnostic Radiology
• Chest x-ray films, posterior/anterior and lateral
views
• Computed tomography (CT) scan of abdomen
and pelvis
• CT scan of chest for non seminomas and stage II
seminomas
• Ultrasound of contralateral testis
• Surgery
Radical inguinal orchiectomy
• Special Studies
Semen analysis

11. STAGING WORK UP
• Serum tumor marker levels should be measured prior to orchiectomy
for assignment of S category.
• The only exception is for Stage IS: Persistent elevation of serum tumor
markers following orchiectomy is required.
• The Serum Tumor Markers (S) category comprises the following:
• Alpha fetoprotein (AFP) [ <15 ng/mL].
• Human chorionic gonadotropin (hCG)
• Lactate dehydrogenase (LDH)

12. • Serum tumor markers can document persistent or
recurrent cancer after surgery or chemotherapy and may
predict the responsiveness of nonseminomas to treatment.
• The level of beta-HCG should decrease by 90% or more
every 21 days with each successful treatment cycle of
chemotherapy.
• The decline of AFP is less predictable.

13. WORKUP (NCCN)
• H&P
• LDH
• Beta HCG
• AFP
• Biochemical Profile
• Chest X-ray
• Testicular Ultrasound
• Discuss sperm banking
• Followed by Radical Inguinal
Orchidectomy
• Consider contralateral testis
biospsy if
• Suspicious ultrasound
• Cryptorchid
• Marked atrophy

14. NCCN GUIDELINES FOR MANAGEMENT
• PURE SEMINOMA (pure seminoma histology and AFP negative;may
have elevated beta-hCG):-
• POST DIAGNOSTIC WORK UP
I. ABD/PELVIC CT
II. CHEST CT IF:- ABD CT +VE , or, ABNORMAL CHEST X-RAY
III. REPEAT beta-hCG, LDH, AFP since TNM staging based on post-orchiectomy
values
IV. BRAIN MRI,if clinically indicated
V. Bone scan ,if clinically indicated
VI. Discuss about sperm banking.

15. PURE SEMINOMA
• STAGE IA,IB
 Surveillance for pT1-pT3 tumors (cat 1)(pref.)
 1. H&P,AFP,LDH,beta-HCGevery 3-4 mth for years 1-2 every 6-12 mth for years 3-4 annually
 2.abd./pelvic CT every 6 mth for years 1-2every 6-12 mths for year 3annually 4-5 years
 3. CXR as clinically indicated for years 1-5RECURRENCE,TREAT ACCORDING TO EXTENTOF DISEASE AT
RELAPSE.
 OR,
 SINGLE AGENT CARBOPLATIN(CAT 1)(AUC =7X1 CYCLE OR AUC= 7X2 CYCLE)
 1. H&P,AFP,LDH,beta-HCGevery 3 mth for years 1 every 4 mth for year 2every 6 for years 3annually
 2. abd./pelvic CT annually for years 1-3
 3. CXR AS CLINICALLY INDICATED
 OR,
 RT(CAT 1)
 1.H&P,AFP,LDH,beta-HCG every 4 mth for years 1-2annually FOR 3-10 YEARS
 2. abd./pelvic CT annually for 3 years( FOR pt. status post only para-aortic RT)
 3. CXR AS CLINICALLY INDICATED

16. PURE SEMINOMA
• STAGE IS:-repeat elevated serum tumor marker & assess with
abd./pelvic pelvic CT scan for evaluable disease.
Stage IS is uncommon and generally treated with radiation.
Recurrence, treat according to extent of disease at relapse

17. PURE SEMINOMA
• STAGE IIA:-
RT to include para-aortic and ipsilateral iliac lymph nodes to a dose
of 30-36 Gy (pref.)
1.H&P,AFP,LDH,beta-HCG every 3 mth for year 1 every 6 mth for
years 2-5 annually FOR 6-10 YEARS
2.CXR every 6 mth for years 1-2
3.abd./pelvic CT every 6-12 mths for years 1-2 then annually for
year 3
• Recurrence, treat according to extent of disease at relapse
Or,

18. PURE SEMINOMA
PRIMARY CHEMOTHERAPY :EP4 CYCLES , OR, BEP3 CYCLES
For multiple +ve nodes
post-chemo follow up©
• STAGE IIB:-
PRIMARY CHEMOTHERAPY :(pref. if adenopathy >3 cm)
EP4 CYCLES OR, BEP3 CYCLES
post-chemo follow up©
Or,

19. STAGE IIB
RT to include para-aortic and ipsilateral iliac lymph nodes to a dose
of 30-36 Gy (pref.)
1. H&P,AFP,LDH,beta-HCG every 3 mth for year 1 every 6 mth for
years 2-5 annually FOR 6-10 YEARS
2. CXR every 6 mth for years 1-2
3. abd./pelvic CT every 6-12 mths for years 1-2 then annually for
year 3
• Recurrence, treat according to extent of disease at relapse

20. STAGE IIC,III
GOOD RISK primary chemotherapy :-EP4 CYCLES OR, BEP3 CYCLES
INTERMEDIATE RISK primary chemotherapy:-BEP4 CYCLES

21. post-chemo follow up©

22. STRATEGIES TO REDUCE RADIOTHERAPY
MORBIDITY(pure seminoma)
• SURVEILLANCE:-
Warde et al. (2002):-
 638 patients with stage I seminoma followed with surveillance with 7-
year follow-up.
 Increased relapse with tumors >4 cm, LVSI, and rete testis involvement.
 Relapses:-
 0 risk factors = 12%,
 1 risk factor = 16%,
 2 risk factors = 30%.
 Prior study showed age <34 years also increased risk of failure.

23. STRATEGIES TO REDUCE RADIOTHERAPY
MORBIDITY
REDUCTION OF RADIATION FIELD SIZE
• MRC TE10 :- 478 patients
randomised to traditional dog-leg
or para-aortic radiotherapy
REDUCTION IN DOSE
• MRC TE18 :- 625 patients
randomised to 30 Gray in 15 #
over 3 weeks ,or, 20 Gray in 10 #
over 2 weeks.

24. MRC TE10 (Fossa et al 1999)
• Survival at 3 years, 99% for PA vs 100% for DL
• RFS 96% PA vs 96.6% DL
• Acute toxicity ( nausea, vomiting, leukopenia) was less frequent and
less severe in PA group
• Within the first 18/12 of F/U the sperm counts were significantly
higher after PA than after DL radiotherapy.
• CONCLUSION: Adjuvant radiotherapy confined to the paraaortic LNs is
associated with decreased haematologic, GI and gonadal toxicity, but
with a higher risk of pelvic recurrence compared with dog-leg
radiotherapy.

25. MRC TE 18 (Jones et al 2001 & 2005)
• 625 patients
• 5 year relapse free survival 97.0% after 30Gy
96.4% after 20Gy
• Better Quality of Life scores for acute effects in lower dose arm:-20
Gy arm had decreased lethargy and inability to carry out normal work
1 month after treatment.
• CONCLUSION :
• Standard radiotherapy for stage 1 seminoma should be:- 20 Gy in 10
fr. over 2 weeks to para-aortic strip (unless previous inguino
/pelvic/scrotal surgery when “dog-leg” field is used)

26. MRC/EORTC (Oliver et al. 2005)
• Carboplatin vs. RT, 2005 →
• 1,477 patients were randomly assigned to receive radiotherapy (paraaortic strip or dog-leg
field) or one injection of carboplatin (dose based on the formula 7× [glomerular
filtration rate + 25] mg.
• With a median follow-up of 4 years, relapse-free survival rates for radiotherapy and
carboplatin were similar (96.7 vs. 97.7% at 2 years; 95.9 vs. 94.8% at 3 years,
respectively).
• Patients given carboplatin were less lethargic and less likely to take time off work than
those given radiotherapy.
• New, second primary testicular germ cell tumors were reported in ten patients allocated
irradiation (all after paraaortic strip field) and in two allocated carboplatin (5-year event
rate 1.96 vs. 0.54%, p = 0.04).
• One seminoma-related death occurred after radiotherapy, and none after carboplatin.
• This trial has shown the noninferiority of carboplatin to radiotherapy in the treatment of
stage I seminoma.
• Update (Oliver et al. 2008): no difference in 5-year RFS (95% chemo, 96% RT), fewer new
GCTs with chemo (2 patients vs. 15 with RT).

27. NONSEMINOMA
• Stage I:-
• Current treatment options include:-
1.SurveillanceIA,IB(T2 Only)
2. modified bilateral retroperitoneal
lymph node dissection (RPLND). The
relapse rate following surgery is
approximately
10% for patients with pathologic
stage-I disease.
 Most patients who relapse after
RPLND are cured with subsequent
chemotherapy.
3.primary chemotherapy (BEP 2CYCLE
OR, BEP 1CYCLE)

28. NONSEMINOMA
• Stage II:-
• The cure rate for stage II
nonseminoma is approximately 98%.
• Patients with stage IIA disease with
marker elevations (AFP,β-HCG, or LDH)
or stage IIB disease regardless of
marker status should be treated with
chemotherapy(BEP 3 CYCLES OR, EP 4
CYCLES)
• IF,primary tumor histologic type is
pure embryonal carcinoma, either
short-term observation to see if the
nodes regress or immediate
treatment with chemotherapy is a
reasonable option.
• IF,primary tumor is of a mixed
histologic type or a teratoma, either
short-term observation or immediate
RPLND is the preferred option. After
RPLND, surveillance or adjuvant
chemotherapy may be employed .
• For patients with pathologic stage IIA
or IIB disease, the risk of relapse with
no adjuvant treatment after surgery is
30% to 50%.
• Relapses occur almost exclusively
outside the retroperitoneum.
• Adjuvant chemotherapy with two
cycles of BEP in all pathologic stage IIA
or IIB patients after RPLND reduces
this risk of relapse to 0% to 7%.

29. NONSEMINOMA
• Stage III Disease AND PERSISTENT MARKER ELEVATION(STAGE
IS,IIA,IIB):-
The standard first-line chemotherapy for all patients is
bleomycin, etoposide, and cisplatin (BEP) using a 5-day schedule.
Modifications in BEP, such as substitution of cisplatin with carboplatin
to reduce toxicity or improve convenience, should be avoided because
they may reduce efficacy.

30. Stage III DISEASE AND PERSISTENT MARKER ELEVATION(STAGE IS,IIA,IIB)

31. GERM CELL TUMOR RISK CLASSIFICATION: INTERNATIONAL CONSENSUS

32. Stage III DISEASE AND PERSISTENT MARKER ELEVATION(STAGE IS,IIA,IIB)

33. RECURRENCE

34. NCCN
Chung P, Warde P. Stage I seminoma: Adjuvant treatment is effective but is it
necessary? J Natl Cancer Inst. 2011;103:194e–196.

35. 3D PLANNING
 3D planning is preferred due to potential of marginal miss, with 2D
planning based on bony anatomy .
 3D planning improves target definition and kidney/small bowel shielding.
Definition of the GTV for lymph node–positive disease:-
GTV node = positive lymph nodes seen on imaging.
Definition of the CTV:-CTV = Retroperitoneal +/− ipsilateral iliac lymph
node region
Definition of the PTV:- PTV = CTV + 0.5 cm.
CTVnode = GTVnode + 0.8 cm, excluding bone and bowel
PTVnode = CTVnode + 0.5 cm.
 Incorporate a 7 mm expansion around the PTVs to block edge to account
for beam penumbra.

36. 3D PLANNING
■ Para-aortic field:
■
retroperitoneal lymph node
coverage
● Contour the inferior vena
cava and aorta separately from 2
cm below the top of the kidneys
down to the point where these
vessels bifurcate.
● Use a 1.2 cm expansion
radially around the inferior vena
cava and a 1.9 cm expansion
around the aorta, excluding
bone and bowel.
■ Dogleg field: Ipsilateral
iliac lymph node coverage
● In addition to the para-aortic
field described above,
contour the ipsilateral
common, external, and
proximal internal iliac veins
and arteries down to the
upper border of the
acetabulum.
● Use a 1.2 cm expansion
on the iliac vessels,
excluding bone and bowel.

37. STAGE I SEMINOMA
PARA-AORTIC NODAL IRRADIATION FOR
OF LEFT TESTIS
10 cm covers the transverse processes in PA vertebrae
upper border of T10 or T11
L5 Vertebrae

38. STAGE II SEMINOMA
10 cm wide in the para-aortic region and usually covers the
transverse processes
upper border of T10 or T11 Classically, the superior border is
placed between the T9 and T10
vertebral bodies, with the inferior
border at the top of the obturator
foramen
left renal hilum
is included for
left-sided
tumors (only)
At the mid-L4 level, the field is extended laterally to cover the
ipsilateral external iliac nodes
inferior border at the superior aspect of the acetabulum
Traditionally, the inferior border was placed at the superior
obturator foramen (indicated in orange) to include all external
iliac nodes

39. STAGE II SEMINOMA
Stage IIA and stage IIB seminoma may be treated with a
traditional or modified dog-leg to a dose of 25 Gy in 20
fractions, with a boost of 10 Gy in 5 fractions to nodes >3 cm in
diameter

40. STAGE II SEMINOMA
• DOSE:-Daily 2 Gy /fr to
cumulative total dose of 30 Gy
for stage IIA and 36 Gy for stage
IIIB.
• TARGET:-Nodal mass(GTV) must
be contoured and a uniform 2
cm margin from GTV to block
edge should be provided for AP-PA
cone down fields.
CONE DOWN

41. • DOSE/FRACTIONATION
• 20 Gy in 2 Gy/fx is preferred or 25.5 Gy in
1.7 Gy/fx
• 20 Gy vs. 30 Gy in 2 Gy fractions
demonstrates similar efficacy with
reduced side effects in a randomized trial
for stage I seminoma .
• Stage II or recurrent cancer after
observation should be treated with an
initial dogleg field, and then a boost
should be delivered to the nodal GTV.
• Lymph nodes ≤2 cm: boost to 30 Gy.
• Lymph nodes between 2 and 5 cm: boost
to 36 Gy.
• Lymph nodes >5 cm: bleomycin ,
etoposide , cisplatin (BEP) chemotherapy
is the preferred treatment.
• DOSE CONSTRAINTS
• Kidneys: D50 ≤8, mean dose ≤9 Gy.
• If patient has only one kidney, then D15
≤20.
• Boost constraints:
• Kidneys: D50 ≤ 2, mean dose ≤3 Gy.
• Treatment planning goal of D95 ≥100 for
PTV coverage with 3D volume based
planning.

42. SHIELDING
• Contra-lateral testis is shielded with a
lead clamshell device, which consists
of a cup that is 1 cm thick. This shields
the testicle from low-energy scattered
photons and effectively reduces the
testicular dose by a factor of 4.
• If scrotal irradiation is necessary
because of previous scrotal surgery
or tumour involvement of the
tunica vaginalis, a scrotal field
using electron therapy is used to
treat the scrotal sac and lower
inguinal nodes on the affected side.

44. THANK YOU