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