SeminomaPresenter – Dr. Venkatesan
Moderator – Prof. Th. Tomcha Singh
Anatomy
• Adult testis – 4 * 3 * 2.5 cc
• Lobule of testis contains
seminiferous tubules
• Lobular ducts converge at
Rete testis > efferent ducts
> epididymis
Anatomy – contd..
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
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
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
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
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%
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
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
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
Staging
Stage grouping
Seminoma – risk classification
Any primary siteAny LDH
Any β HCG
Good RiskNo Non pulmonary
visceral mets
Intermediate RiskNon pulmonary
visceral mets
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
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
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%
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
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
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
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
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
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)
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 %
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%
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
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
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
RT technique – contd…
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
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
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
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
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
Follow up Stage
H & P,Sr. AFP, LDH, β HCG CXR CT Scan
IA, IB after RT4 mthly for 1st 2 yrsThen annually 3 – 10yrs
When clinically indicated
CT pelvis annually – 3 yrs only for PA RT.
IA, IB after CT 3 mthly for 1st yr4 mthly for 2nd yr6 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 yr6 mthly for 2 – 5 yrsAnnually 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 yr3 mthly for 2nd yr6 mthly for 3-4 yrAnnually upto 10 yr
2 mthly for 1st yr3 mthly for 2nd yr6 mthly for 3-4 yrAnnually upto 10 yr
When clinically indicated
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%
Thank you
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