Seminoma

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 – 4 th decade - NSGCTs – 3 rd 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 1 st 2 years - 6 mthly assessment in 3 rd & 4 th yr - annual assessment in yrs 5 – 10 - Median time to relapse – 12 – 18 mths - 76 – 94 % of relapses in retroperitoneum – Adj. RT - 2 nd 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 R elapse 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 2 nd 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 - 2 nd 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 1 st 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 1 st yr 4 mthly for 2 nd 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 1 st yr 6 mthly for 2 – 5 yrs Annually for 6 – 10 yrs 6 mthly for 2 yrs 6 mthly for 2 yrs , Annually in 3 rd yr IIB, IIC & III after CT 2 mthly for 1 st yr 3 mthly for 2 nd yr 6 mthly for 3-4 yr Annually upto 10 yr 2 mthly for 1 st yr 3 mthly for 2 nd 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