3. Introduction
• The word testis derived from Latin word testiculus which means to
witness
• Testicular cancers comprise a morphologically and clinically diverse
group of tumours
• 1-2% of all malignancies
• 1-2% bilateral
• 90-95% are Germ Cell Tumours (GCTs)
• Predominantly affects young males
• Peak incidence: 3rd decade for non-seminoma, 4th for pure
seminoma
4. • Worldwide, 72,000 new cases and 9000 deaths per year
• India, incidence rate 0.5 new cases per 100,000 men per year
• US, Incidence rate 5.7 new cases and 0.3 deaths per 100,000 men per
year
• Incidence increasing by 44% from 1973-1978 to 1994-1998 in US
• European countries increment is by 1 to 6% per year
• Mortality rates decreasing or stable in most regions, reflecting
improvements in treatment
• Worldwide incidence lowest in Africa and Asia, and highest in the
Scandinavian countries, Germany, Switzerland, and New Zealand
[Siegel RL, et al. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67:7]
[Fitzmaurice C, et al. Global, regional and national cancer incidence…,JAMA Oncology, 2017]
Epidemiology
9. Risk Factors
• Germ cell neoplasia in situ
• Cryptorchidism
• Hypospadias
• Contralateral testicular Cancer
• Extra gonadal germ cell tumour
• Family History
• HIV infection
• Testicular microlithiasis
10. Risk Factors (Contd)
• Androgen insensitivity syndrome and mixed gonadal dysgenesis
• Inutero estrogenic effects
• Klinefelter’s and down syndrome
• Peutz Jeghars Syndrome
• Carney’s complex
• Ethnicity
• Dietary issues and cholesterol
• Marijuana smoking
11. Genetics and molecular biology
• A specific genetic marker (an isochromosome of the 12p) - in all histological
types of germ cell tumours and in TIN
• Alterations in the p53 locus have been identified in 66% of cases of
testicular TIN 2
• Protooncogenes in GCTs
– Seminoma and embryonal carcinoma- c-myc expression
– Seminoma- c-ki ras expression
– Immature teratomas- c-erb- B1 and c-erb-B2 expression
• GCTs consistent with gain of 11,13,18 chromosomes and loss of 7,8,X
chromosomes
• Spermatocytic seminoma- gain of chromosome 9
13. Plumbing
Lymphatic drainage:
Retroperitoneal lymph nodes
between the levels of T11 and L4,
but concentrated at the level of the
L1 and L3 vertebrae
Blood supply:
Testicular artery b/o abdominal
aorta, collateral blood supply from
cremasteric artery and artery to the
ductus deferens
Venous: Pampiniform plexus Rt
side- IVC, Lt side- Lt renal vein
Nerve supply:
Sympathetic nerves arising from
segment T10 of the spinal cord. •
Both afferent for testicular
sensation and efferent to the blood
vessels(vasomotor)
14. Descent of testis
• Develops at T10-T12 segments
in posterior abdominal wall from
genital ridge and subsequently
descend to reach scrotum
• Begins descent in 2nd
month of
intrauterine life
• 3rd
month to reach iliac fossa
• 4th
-6th
month deep inguinal ring
• 7th
month inguinal canal
• 8th
month- superficial inguinal ring
• 9th
month- scrotum
• Cryptoorchidism- 1 or both
testicles fail to reach scrotum
before birth
15. Clinical features
• A nodule or painless swelling of one testicle
• 30 to 40 % patients dull ache or heavy sensation in the lower
abdomen, perianal area, or scrotum
• Acute pain in 10 %
• Gynecomastia
– about 5% of men with testicular GCTs
– 20 to 30% of patients with Leydig cell tumors of the testes (2% of
testicular tumours)
– sometimes a/w production of hCG by foci of choriocarcinoma or
trophoblastic cells in the tumor
– marked overproduction of hCG can cause paraneoplastic hyperthyroidism
• Paraneoplastic limbic encephalitis
16. Clinical Features(Contd)
• 10% attributable to metastatic
– A neck mass
– Cough or dyspnea
– Anorexia, nausea, vomiting, or gastrointestinal hemorrhage
– Lumbar back pain
– Bone pain
– Central or peripheral nervous system symptoms
– Unilateral or bilateral lower extremity swelling
19. Differentials
• Epididymo-orchitis
• Hematoma
• Leukemia
• Metastasis from other cancers (eg, lung cancer, melanoma, prostate
cancer)
• Syphilitic gumma
• Trauma
• Tuberculosis and other testicular infections
All patients with a solid, firm intratesticular mass that
cannot be transilluminated should be regarded as
malignant unless proved otherwise
28. [International Germ Cell Consensus Classification: a prognostic factor-based staging system for
metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group., JCO 1997]
29. Management
• Sperm testing and banking should be considered before treatment
with chemotherapy, RPLND, and EBRT because of potential effects
on fertility
• Post orchidectomy markers level is considered
• Treatment modalities
– Surgery
– Surveillance
– Radiotherapy
– Chemotherapy
31. Primary Treatment
• Radical inguinal orchiectomy to allow
high division of the spermatic cord
• Orchiectomy offers cure in a high
proportion (60% to 90%) of patients
• Transscrotal approach does not appear
to compromise the outcome, provided
that the scrotal cavity has not been
grossly contaminated by tumor during
surgery (but not recommended)
• In patients with life-threatening
metastatic disease and a clear-cut
diagnosis of germ cell malignancy,
initial management is with
chemotherapy and surgery is
postponed until completion of systemic
treatment
33. • Pooled analysis of four large
surveillance data sets of 638
patients
• Tumor size and rete testis invasion
predicted for relapse on MVA
• The HR for relapse with a tumor
size >4 cm is 2 (95% CI, 1.3 to 3.2)
relative to baseline (tumor size <4
cm and no rete testis invasion)
• The high-risk group had up to 35%
risk of relapse
[Warde P. et al, JCO, 2002]
34. • N= 1954
• Median F/U= 15.1 year
• Total no of relapses= 369
• 18.1% relapses within 5 yr of follow-up, and 0.8% relapses after >5
yr
• Median time to relapse =13.7 mo.
• The 15-yr DSS =99.3% and OS=91.6%
• Tumour size independent risk factor for relapse
• VI+ and EPI were also identified as prognostic factors for relapse.
Their roles were less clear; however, both were statistically
significant if the other factor was excluded
[Mortensen MS, et al. European Urology, 2014]
35. • Prospective, single-arm
• N=88
• 20% rete testis invasion, 45% >4cm
• Median F/U 12.1 years, 3 lost to follow-up
• Relapse-free rate: 5-years 83%, 10-years 80%, 15-years 80%
• Relapse site: 88% (15/17) below diaphragm
• Predictor for relapse: invasion of rete testis (HR 3.5, p= 0.03)
[Choo R, et al. IJROBP, 2004]
39. Adjuvant RT
• Historically, seminoma was treated with orchiectomy +
inguinal/paraaortic RT, and sometimes also mediastinal RT
• Prophylactic mediastinal RT was abandoned due to increased
cardiac mortality in the 1960's and 1970's
• Para-aortic fields plus ipsilateral iliac LNs ("dog leg") at 30/15
became standard
40. • July 1989 and May 1993
• N=478
• Testicular seminoma stage I (T1 to T3; no ipsilateral inguinoscrotal operation
before orchiectomy)
• Randomization (PA, 236 patients; DL, 242 patients)
• Median f/u = 4.5 years
• 18 relapses, 9 in each treatment group; 4 were pelvic relapses, all occurring after
PA radiotherapy
• 3-year relapse-free survival was 96% after PA radiotherapy and 96.6% after DL
• OS 99.3% for PA and 100% for DL radiotherapy
• Pelvic relapse free survival p=0.04
• Acute toxicity (nausea/vomiting (p=0.08), diarrhoea(p=0.013),
leukopenia(p<0.0001)) less frequent in patients in the PA arm. Within the first 18
months of follow-up, the sperm counts significantly higher(p<0.001) after PA than
after DL irradiation [Fossa SD, et al. JCO, April 1999]
41. DL vs PA
• Dog leg field
– UB: D10-D11
– LB: mid obturator foramen
– Ipsilateral margin, to the renal hilum
down as far as the disk between the
fifth lumbar and first sacral vertebrae
(L5-S1), then diagonally to the lateral
edge of the acetabulum, then vertically
downward to the mid obturator level
– Contralateral margin, inclusion of the
processus transversus in the PA area
down to L5-S1, then diagonally in
parallel with the ipsilateral border, then
vertically to the median border of the
obturator foramen
• Paraaortic field
– identical to the upper part of the DL
field (above the level of L5-S1)
43. Superior edge of para-aortic field
•Retrospective
•80/163 patients, Stage I seminoma
•Treated with PA field extending from T11/T12 (vs historical T10/T11)
to L4/L5
•Median dose 20 Gy
•Median F/U 7.1 years
•Outcome: 5-year RFS 95%, no relapse above T12
•Dosimetry: Median reduction of treated volume 16% (13-21%)
•Conclusion: Recommended to minimize risk of radiation-related late
effects
[Bruns F et al, Acta Oncol. , 2005]
44. Radiotherapy Techniques
• Position and immobilization
– Supine, arms placed by the pt. side
and legs straight, with feet stabilized
with a foam wedge underneath the
knees
– Body cast can also be used for
immobilization
– Position penis out of field
– Shielding – Contra-lateral testis is
shielded with a lead clamshell device
45. PA field
Stage I
•Field margins
•Superior: T11–T12 interspace
•Inferior: L5–S1 interspace
•Lateral: transverse process
•For left testis: cover renal hilum
•Dose – 20 Gy in 10# to para-
aortic ± pelivic lymph node by
AP-PA field
46. Conformal
• Contour the IVC and aorta
separately from 2 cm below the top
of the kidneys down to the point
where these blood vessels end
• CTV created by giving 1.2cm
expansion to IVC and 1.9cm
expansion to aorta
• 5mm margin to form PTV and 7
mm block margin
[Wilder RB et al. Radiotherapy treatment
planning for testicular seminoma.
IJROBP 2012 Jul 15;83(4):e445-52]
47. Adjuvant Chemotherapy
• Chemotherapy is preferred in patients with a horseshoe(pelvic)
kidney, inflammatory bowel disease or history of radiotherapy
• Multiple non randomized trials have been published using either
single or 2 cycles of Carboplatin
49. Adjuvant Chemotherapy
• Updated results, N= 1447, 3:5 carboplatin:RT
• RFRs at 5 years were 94.7% for carboplatin and 96.0% for RT (RT-
C 90% CI, 0.7% to 3.5%; HR, 1.25; 90% CI, 0.83 to 1.89)
• Reduction in the rate of contralateral GCTs (carboplatin, n = 2; RT,
n = 15; HR, 0.22; 95% CI, 0.05 to 0.95; P = .03
[Oliver RTD, et al. JCO, March 2011]
51. Relapse
• After Surveillance
– Irradiation or cisplatin-based chemotherapy
– Most patients who relapse while on surveillance initially treated with
retroperitoneal RT and have 10% incidence of second relapse after RT
• After RT
– Commonest sites of relapse following adjuvant RT are the mediastinum, lungs,
and left supraclavicular fossa and rarely in the inguinal nodes
– For supradiaphragmatic relapse, chemotherapy results in virtually 100% cure
rate
– Isolated inguinal relapse may be treated successfully with RT alone
– Relapse after adjuvant RT most frequently occurs within the first 2 to 3 years with
the occasional relapse beyond this time frame
53. Radiotherapy (Dog leg vs
Modified Dog leg
• Dog leg /Hockey stick field
– UB: upper part of T11 or T12
vertebrae
– LB: mid/upper part of
obturator foramen
– Lateral: transverse process
down to L5-S1 interface then
diagonally to the lateral edge
of acetabulum, then vertically
downward till mid/upper part
of obturator foramen
– For left testis cover renal
hilum
• Modified Dog leg
– All same except LB- superior
aspect of actabulum
54. RT Stage II seminoma
• Depends on bulk of retroperitoneal
nodes
• Radiotherapy treatment of choice in
stage 2a & 2b (node < 5cm)
• By traditional/modified dog leg to a
dose of 20Gy/10# f/b boost
10Gy/5# to IIA and 16Gy/8# boost
to IIB disease
• Another dose regimen is 25Gy/20#
f/b boost 10Gy/5# to nodes >3cm
• Disease specific survival rate 97 –
100%
• Recurrence rate < 10% ,MC site
SCF & mediastinum.
• CT + RT = RT alone (Patterson et
al, 2001)
56. Conformal
• CTV1 + Iliac vessels down to the upper
border of the acetabulum
• 1.2-cm expansion on the iliac vessels
and included in CTV1
• The PTV1 is created as previously
described
[Wilder RB et al. Radiotherapy treatment planning for testicular seminoma.
IJROBP 2012 Jul 15;83(4):e445-52]
57. • Contour the retroperitoneal
adenopathy (i.e., the gross
tumor volume)
• GTV + 0.8cm = CTV2
• CTV2 + 0.5cm =PTV2
• PTV2 + 0.7cm = Block Edge
• By coning down after 20 Gy,
one reduces toxicity
[Wilder RB et al. Radiotherapy treatment planning for testicular seminoma.
IJROBP 2012 Jul 15;83(4):e445-52]
58. Toxicity of Radiotherapy
• Acute
– nausea, vomiting, diarrhea
• Late
– small bowel obstruction,
– chronic diarrhea,
– peptic ulcer disease (<2% with <35 Gy)
– Second cancers: 5–10% increased risk
– With testicular shielding, most patients will have oligospermia by 4
months that lasts ~1 year
– Infertility: 50% of patients have subfertile counts on presentation or after
surgery
– After RT, 30% able to have children
60. Seminoma Stage IIC
• Stage IIC ( node > 5cm)
• Systemic chemotherapy is the treatment of choice, RT is an option
but relapse rate is 30%
• If nodes > 10 cm, RT relapse rate is 40 %
• CT of choice is BEP x 3 or EP x 4
61. Seminoma Stage III
• Treatment is BEP × 3 cycles or EP × 4 cycles Salvage Surgery
• Einhorn and colleagues demonstrated that the fourth cycle was
associated with excess toxicity but with no increased cancer-specific
survival
• Cisplatin based regimen was superior to the carboplatin arm
[Bajorin 1993; Bokemeyer 1996; Horwich 1997; Horwich 2000]
64. Non-Seminoma Stage I
• Post orchidectomy treatment options
– Surveillance
– RPLND
– Chemotherapy
• STAGE I (50%)
– Survival close to 100%
– Risk factors for relapse
• Venous invasion
• Presence of undifferentiated elements
• Absence of yolk sac elements
66. RPLND
• RPLND is offered to
– LVI in the primary tumour
– Non compliant patients
– The presence of LVI is associated with 45-
55% recurrence vs 15-20% without this risk
factor
[Colls 1999; Daugaard 2003; Gels 1995]
• RPLND
– Include the precaval, retrocaval, paracaval,
interaortocaval, retroaortic, preaortic, para-
aortic, and common iliac lymph nodes
bilaterally
– Disadv.: Retrograde ejaculation
– With modern nerve-sparing techniques, the
incidence has declined to rates of 5%
[Stephenson Aj et al Curr Treat Options
Oncol. 2005;6:367-377]
67. Chemotherapy
• Failure of postorchidectomy markers to normalize (stage IS)
indicates the presence of systemic disease, often outside the
retroperitoneum and requires primary management with systemic
chemotherapy
[Davis 1994]
• Trials evaluating 1 or 2 cycles of bleomycin, etoposide, and cisplatin
(BEP) in all T2N0-T4N0 demonstrated continuous disease-free
survival and overall survival rates of 95% and 99%, respectively
[Cullen MH, et al. Short-course adjuvant chemotherapy in high-risk stage I
nonseminomatous germ cell tumors of the testis: a Medical Research
Council report. J Clin Oncol. 1996;14:1106-1113]
72. Stage IIC and III
• Chemotherapy
• If residual disease, salvage surgery
• The role of radiation is only palliative in metastatic setting
73.
74. Salvage Chemotherapy
• 20% to 30% of patients will develop progressive disease following
initial chemotherapy with or without surgery and will require salvage
therapy
• Conventional doses of cisplatin plus ifosfamide plus either
vinblastine (VeIP) or paclitaxel (TIP) are the most commonly used
regimens.
77. Follow Up
• Now different follow up policies recommended for different stages
and treatment modalities
• Principle is to follow up the patients under surveillance alone very
closely with abdominopelvic CTs, CXR
• Close follow up is also required for higher stage and poor prognostic
group patients after initial treatment
• Duration between follow up can be relatively increased for lower
stage and good prognostic group patients treated with one or more
adjuvant modality
• Closest follow up is 2 monthly
• Generally 3 monthly F/U in 1st
year and 3-6 monthly in 2nd
and 3rd
year
and 6 months - annually in 4th
and 5th
year would suffice
• For more accurate follow up strategies, one can follow guidelines
like NCCN, ESMO
78. Conclusion
• Most common curable malignancy of young adults
• Seminoma > Nonseminoma
• Surgery is the main modality of treatment followed by Radiotherapy
& or chemotherapy for seminoma and chemotherapy & RPLND for
nonseminoma
• Surveillance for patients who are compliant
• Follow-up is recommended to detect second primary tumors, local
or distant recurrences, and to monitor for potential long-term side
effects
paraneoplastic limbic encephalitis
Most of these patients have anti-Ma2 (also called anti-Ta) antibodies. The Ma2 antigen is selectively expressed in the neuronal nucleoli of normal brain tissue and the testicular tumor of the patient
