Seminoma, types, clinical presentation, management with Sx, RT & Chemotherapy

1. Seminoma
Presenter – Dr. Venkatesan
Moderator – Prof. Th. Tomcha Singh

2. Anatomy
• Adult testis – 4 * 3 * 2.5 cc
• Lobule of testis contains
seminiferous tubules
• Lobular ducts converge at
Rete testis > efferent ducts
> epididymis

3. Anatomy – contd..

4. Epidemiology
• Testicular tumor -> 1- 2 % of malignancies in men
• Majority – GCTs - 90% originate in testis
- 10 % extragonadal
• Others – lymphoma, sarcoma
• GCTs
- Seminoma – 4th decade
- NSGCTs – 3rd decade
• Incidence of GCT doubled in past 30 yrs
• Common in young white men & less common in
african americans

5. Risk factors
• Cryptorchidism – 6 fold ↑ed risk
• Family H/O testicular ca
• Subfertility
• Testicular microlithiasis
• Prior testicular malignancy
• Heritability
- risk to son - 4- 6 times ↑ed
- risk to brother – 8 – 10 times ↑ed
• Other risk factors
- H/O testicular trauma
- ↑ed BMI
- Immunosuppression
- Prenatal factors

6. Pathology
• Seminoma arises from germinal epithelium of
seminiferous tubules
• GCTs
->60% - pure seminoma
->30% - NSGCTs
->10% - mixed tumors
• ITGCN
- precede all seminoma & NSGCTs
- 0.5% in impaired fertility
- 2.5% in cryptorchid & C/L testis of prior GCT

7. Seminoma - types
• Classic
• Atypical Seminoma
• Anaplastic seminoma
- ≥ 3 mitotic figures / HPF
• Spermatocytic Seminoma
- old men
- not ass. With IGCN
- do not express PLAP
- minimal metastatic
potential
- excellent prognosis

8. Pathways of spread
• Direct extension
- epididymis -> tunica
vaginalis -> spermatic cord ->
scrotum
• Lymphatic spread
- m.c. route
- Lt sided – para, pre aortic
& Lt common iliac LN
- Rt sided – interaorto
caval, pre, para caval & Rt c. iliac
- C/L LN mets – 15%

9. Pathways of spread – contd..
• Supra diaphragmatic spread
- via thoracic duct > post. Mediastinum > Lt S/c LN
• Pelvic & inguinal LN involvement rare (< 3%)
• Distant mets
- Lung > Liver > Brain > Bone > Kidney

10. Clinical features
• Painless testicular mass
• 45% of pts – testicular pain
• 10% of pts
- neck mass
- cough or dyspnoea
- anorexia, nausea, vomiting/haemorrhage
- lumbar backache
- bone pain
- U/L or B/L lower limb swelling
• 70 – 80% - stage I
• 15 – 20% - stage II
• 5 % - stage III

11. Work up
• History
• Physical examn
• Lab studies
- CBC, LFT, KFT, S. electrolytes, RBS
- Sr. LDH
- Sr. AFP
- Sr. β HCG
• Surgery
- Radical inguinal orchiectomy
• Diagnostic radiology
- CXR PAV & lat. View
- CT scan abdomen & pelvis
- CT scan Chest
- USG of C/L testis
• Semen analysis
USG of testicular swelling

12. Staging

13. Stage grouping

14. Seminoma – risk classification
Any primary site
Any LDH
Any β HCG
Good Risk
No Non pulmonary
visceral mets
Intermediate Risk
Non pulmonary
visceral mets

15. General management
• Initial management
- Radical inguinal
orchiectomy
• Stage I
- surveillance
- adj. RT
- adj. CT
• Stage II A/B
- adj. RT
- adj. CT
• Stage II C / III
- sytemic CT

16. Stage wise Rx
• Stage I
1)Surveillance
- management strategy of choice
- Physical examn & CT scan
- 4 mthly assessment in 1st 2 years
- 6 mthly assessment in 3rd & 4th yr
- annual assessment in yrs 5 – 10
- Median time to relapse – 12 – 18 mths
- 76 – 94 % of relapses in retroperitoneum – Adj. RT
- 2nd relapse occur in 10 % of pts ( distant) - CT

17. Stage I – Rx (contd….)
• Warde et al, JCO 20:4448-4452, 2002 (pooled data from 4
major centers)
> 5 year OS – 97.7%
> 5 year CSS – 99.3%
> 5 / 10 year RFS – 82.3% / 78.7%

18. Stage I – Rx (contd….)
2)EBRT
> OS rates are 92-99%
> Cause-specific survival is nearly 100%
> Relapse rates are 0.5-5% in modern studies (mostly
supradiaphragmatic)
> Most relapses occur <2 years from treatment (median 18
mo. in PMH study)
> Chemotherapy is readily used in the setting of relapse

19. Stage I – EBRT (contd….)
• Historically Adj. RT to para aortic & I/L pelvic lymph nodes (
dog leg or hockey stick)
• Relapse rate – 1 – 5 % & disease specific survival – 100%
• Para aortic RT alone – higher failure in pelvic nodes
• Hence, a common approach using modified dog leg portal
where inf. Border placed at mid pelvic level is used

20. Stage I – Rx (contd….)
3)Adj. CT
- less toxic alternative to RT
- Oliver et al (Carboplatin without RT)
- 78 patients
- 53 with 2 courses of Carbo
- 25 with 1 course of Carbo
- 44 months of follow up with only 1 relapse

21. Stage I – RT vs CT
• The MRC (Oliver et at JCO, 29:957-962, 2011)
randomized:
• With a median of 6.5
years follow up
– Relapse rate was
5.3% with carboplatin
vs 4.0% with RT
885 patients got PA
or DL RT to between
20 and 30 Gy
560 patients got one
injection of carboplatin

22. Stage I - Rx Summary
• Treatment
– Inguinal Orchiectomy
• Active Surveillance with serial imaging
– ~85% RFS
– 70% relapses <2years, nearly all <5 years
• XRT
– 95% RFS
– Paraaortic equivalent with less toxicity than
PA/Pelvic (dog leg)
– 20 Gy equivalent with less toxicity than 30 Gy
• Carboplatin
– 95% RFS
– One cycle equivalent to two cycles

23. Stage II - Rx
• Stage IIA – RP node <2cm
• Stage IIB – RP node 2.1-5cm
• Stage IIC - >5 cm
• Few patients have stage II disease making randomized trials
difficult to perform
• Data hence stems from institutional experiences
• The greatest prognostic factor is bulk of nodal disease
(diameter of largest node)

24. Stage II - Rx – contd….
• Stage IIA & IIB
- EBRT 25 – 35 Gy RxOC
- Recurrence rate < 10 %
- Disease specific survival rate 97 – 100 %
- CT more toxic
• Stage IIC
- Systemic CT
- with RT , relapse rate > 30 %

25. Stage III - Rx
• Systemic CT
• 3 courses of BEP or 4 courses of EP
• 5 yr survival
> good prognosis group – 91%
> intermediate prognosis group – 80%

26. Residual Retroperitoneal Mass
• Presence of residual masses after definitive treatment
is common
• Most often represent fibrosis or necrosis
• Very few contain viable tumor
• Options
– Observation ( for mass ≤ 3 cm )
– Surgery
– RT (after chemo)
• PET is of little value in this setting

27. RT technique
• Cobalt – 60 or 6 – 18 MV linear
accelerator photons
• Parallel AP/PA fields
• Testicular shielding
• CT based planning
• IVU evaluation
• Target volume
- interaortocaval, pre & para
aortic,
- Lt renal hilar LN
- I/L int. & ext. iliac LN

28. RT technique
• Dog leg field
> upper – T9 & T10
> lower – top of obturator
foramen
• Modified dog leg
- upper – b/w T10 & T11
- lower – superior aspect of
acetabulam
- at para aortic region field
approx. 9 cm wide
- at renal hilum width – 11 –
12 cm
- field extended laterally at
mid L4 level to cover I/L external
iliac nodes

29. RT technique – contd…

30. RT dose & fractionation
• Stage I
- 20 Gy / 10 # over 2 weeks
- 30 Gy /15# over 3 weeks
- 25Gy / 20# with 1.25Gy/#
• Stage II
- 25 Gy / 20# with boost 10 Gy to residual LN
- alternatively 30 Gy/15# for Stage IIA
- 36Gy /18# for Stage IIB

31. Dose limitations
• 50 cGy causes transient azospermia with recovery at 1 yr
• 80 – 100 cGy causes total azospermia with recovery at 1 -2 yrs
• 200 cGy causes sterilisation
• Clamshell reduces testicle dose by 2 – 3 times
• Kidney – limit atleast 70% < 20 Gy

32. Chemotherapy
• Stage I
- Carboplatin 1 or 2 cycles
• Stage II/III
- EP (etoposide, cisplatin) x 4 cycles
- BEP (bleomycin, etoposide & cisplatin) x 3 cycles
• 2nd line CT
> VIP – vinblastine, Ifosfamide, Cisplatin x 4 cycles
> TIP – paclitaxel, ifosfamide, cisplatin x 4 cycles

33. B/L testicular tumor
• 1 -5 %
• Standard – B/L orchiectomy with life long androgen
supplement
• Organ sparing surgery emerged
- Partial orchiectomy in tumors < 2cm size
- adj. low dose RT -> 16 – 20 Gy

34. Rx complications
• RT
- late gonadal toxicity
- cardiovascular toxicity
- 2nd malignant tumor
- Psychological toxicity
• CT
- nausea, vomiting
- myelosuppression
- febrile neutropenia
- nephrotoxicity
- chronic peripheral neuropathy
- pulmonary toxicity

35. Follow up
Stage
H & P,
Sr. AFP, LDH, β HCG CXR CT Scan
IA, IB after RT
4 mthly for 1st 2 yrs
Then annually 3 –
10yrs
When clinically
indicated
CT pelvis annually
– 3 yrs only for PA
RT.
IA, IB after CT 3 mthly for 1st yr
4 mthly for 2nd yr
6 mthly for 3 rd yr &
annually thereafter
When clinically
indicated
CT abd/pelvis
annually for 3 yrs
IIA, IIB after RT 3 mthly for 1st yr
6 mthly for 2 – 5 yrs
Annually for 6 – 10 yrs
6 mthly for 2 yrs 6 mthly for 2 yrs,
Annually in 3rd yr
IIB, IIC & III after CT 2 mthly for 1st yr
3 mthly for 2nd yr
6 mthly for 3-4 yr
Annually upto 10 yr
2 mthly for 1st yr
3 mthly for 2nd yr
6 mthly for 3-4 yr
Annually upto 10 yr
When clinically
indicated

36. Results of therapy
• Stage I
– 96- 98% 10 yr DFS
- 99 – 100% cause specific survival
• Stage II A – 92% DFS, 96 – 100% CSS
• Stage IIB – 86% DFS, 96 – 100% CSS
• Stage III – overall progression free survival – 86%

37. Thank you