Seminoma testis (1).pptx

Seminoa testis

1. Seminoma testis

2. introduction Cancers of testis are relatively rare cancer accounting for approx. 1 – 1.5% of all male neoplasm 90% - GCT India ⮚ Incidence – 0.6 per 100000  ⮚ Mortality – 0.3 per 100000  Epidemiology Most common among adolescents and young men median age at diagnosis is 34 years, with 50% of incident  cases between 20 and 34 year Geographic : Highest incidence in Denmark, Germany, and Switzerland  and the lowest in eastern Europe and Asia.  Race : more common in young white men ,less in African Americans

3. Risk factors 1. Cryptorchidism  2. Klinefelter syndrome  3. Positive family history  4 . Intratubular germ cell neoplasia  Contra lateral tumour - cumulative lifetime risk 1.9%

4. presentation Most commonly presents as painless testicular swelling Pressure like sensation , heaviness, mild to moderate testicular pain Sometimes may mimic epipididymo -orchitis Clinical examination :- Enlarged testis Nodular testis  Firm to hard in consistency  d) Loss of testicular sensation  e) Secondary hydrocele  f) Flat and difficult to feel epididymis Look for SCF nodes

5. Pathway of spread The veins emerge from the back of the testis and receive tributaries from the epididymis Pampiniform plexus Right side – IVC Left side – left renal vein

6. Lymphatic drainage Drain into the retroperitoneal lymph nodes between the  levels of T11 and L4 On the right:  Interaortocaval region , followed by the paracaval , preaortic and para aortic LN On the left:  Preaortic and para-aortic nodes and thence to the interaortocaval       

7. Metastatic nodal disease to the common iliac, external iliac, or  inguinal lymph nodes is usually secondary to a large volume of  disease with retrograde spread.  If the patient has undergone a herniorrhaphy, vasectomy, or other  transscrotal procedure , metastasis to the pelvic and inguinal lymph  nodes is more likely  Through the thoracic duct to lymph nodes in the posterior  mediastinum and supraclavicular fossae and occasionally to the  axillary nodes.  Contralateral spread is mainly seen with right-sided tumors. In 15% to 20%, bilateral nodes are involved

8. Direct spread – occurs by invasion tunica albugenia is rarely penetrated may be crossed by blunder biopsies scrotal skin involvement spermatic cord and epididymis – poor prognosis

9. Investigation CBC, RFT, LFT Chest X-ray Tumor markers - βHCG, AFP and LDH Increased βHCG - 10–20% seminomas AFP - non- seminomatous LDH - prognostic

10. USG of scrotum is Confirms the presence of a mass Evaluate opposite testis High sensitivity in detecting tumor (100%) Intra vs extra testicular tumor Seminomas - well-defined hypoechoic lesions without cystic areas Hydrocoele/epididymitis MRI testis High sensitivity (100%) and specificity (95%) But not routinely needed CT Abdomen and pelvis

11. CT Thorax – RP LN detected, symptom, abnormal CXR PET Metastatic vs reactive LN Post therapy residual masses Biopsy Contraindicated Limited value - heterogeneous

12. Diagnosis Radical inguinal orchiectomy is the standard diagnostic and therapeutic procedure for a solid intratesticular mass Spermatic cord is ligated high in the internal inguinal ring Trans scrotal orchiectomy or biopsy is C/I due to risk of tumor cell seeding of inguinal or pelvic drainage Removal of entire organ is necessary to properly identify the histologic types present RPLND – not indicated in seminoma

13. Organ sparing Not indicated in the presence of normal contalateral testis Considered in - B/l Tumours Metachronous C/L tumours Solitary testis with normal pre-operative testosterone levels Tumour volume < 30% of testicular volume

14. Essential pathologic details Histology Tumour size Tunica albuginea, tunica vaginalis, rete testis, epididymis or spermatic cord Lymphovascular invasion Testicular intraepithelial neoplasia (TIN)

15. Staging

16. Spermatocytic seminoma Older individuals Mean Age 54 years Low metastatic potential Orchiectomy is the only treatment required Not associated with GCNIS

17. GCNIS Germ cell neoplasia in situ Intratubular germ cell neoplasia of the unclassified type Along germ cell tumors 90% and in the contralateral testis around 5% Biopsy of the contralateral testis - high risk for contralateral GCNIS Testicular volume < 12 mL History of cryptorchidism Poor spermatogenesis

18. Unilateral GCNIS and a well-functioning contralateral testicle, the options are surveillance or orchiectomy Bilateral GCNIS or GCNIS in a solitary testis, the options of low-dose (18 to 20 Gy ) RT or surveillance Unilateral GCT If a biopsy is performed and GCNIS is identified, the options include surveillance, chemotherapy, or low-dose RT Testicular self-examination and annual ultrasonic follow-up 5-year risk of developing cancer of 50%

19. Stage I seminoma After orchiectomy Active surveillance Adjuvant chemotherapy Adjuvant RT Disease specific survival is close to 98 to 99% HOW TO CHOOSE

20. RISK FACTOR FOR RELAPSE Multiple studies have been conducted to identify risk factors in stage I seminoma to aid in adjuvant management. Have not been validated

21. The purpose of the protocol was to reduce the treatment burden in clinical stage I (CSI) seminoma by offering risk-adapted treatment aimed to prospectively validate the proposed risk factors for relapse, stromal invasion of the rete testis and tumor diameter >4 cm, and to evaluate the efficacy of one course of adjuvant carboplatin . RISK ADAPTED APPROACH ….

22. In multivariate analyses, both stromal invasion of rete testis and tumor diameter >4 cm retained statistical significance with a hazard ratio (HR) of 2.7,  P  < 0.001 for tumor diameter >4 cm and an HR of 1.9,  P  = 0.011 for stromal invasion of rete testis

23. From 2004 to 2008, 227 patients were included in a Spanish multicentre study  Median follow-up: 34 months  15 relapses (9.8%) among patients on surveillance and 1(1.4%) among those treated with carboplatin 3-year DFS rate: 88.1% (95%CI, 82.3% to 93.9%) for surveillance and 98.0% (95% CI, 94.0% to 100%) for  adjuvant chemotherapy

24. Conclusion :- a risk-adapted treatment policy is feasible in a multicenter setting, Adjuvant carboplatin seems adequate treatment for patients with two risk criteria, as is active surveillance for those with 0 to one risk factor

25. Active surveillance Avg risk of recurrence with surveillance for stage I seminoma is 15 – 20% Most detected in infradiaphragmatic LN

26. Retrospective population based study (1984 to 2008 ) N = 1954 patients Median follow up 15.4 yrs

27. Crude relapse rate - 19.5% Median time to relapse was 14 months Disease-specific survival at 15 years was 99.3 % conclusion :- Surveillance is a rational choice in most CSI seminomas  

28. Active surveillance Close follow up Frequent imaging Good patient compliance Early detection of recurrence Relapse rates of 15% to 24%

29. NCCN discourages risk adapted management approach for surveillance and prefers surveillance for Stage I tumors Predominant site of relapse - Paraaortic LN Majority of relapses occur within 3 years for Stage I seminoma. Late and advanced stage relapse are rarely seen

30. Follow Up

31. TRISST TRIAL

32. Adjuvant Chemotherapy Carboplatin is a simple and safe form of adjuvant chemotherapy that is similar in efficacy to prophylactic RT

33. RT CARBOPLATIN Relapse free rates at 5 years 96% 94.7% Contralateral primary 1.96% 0.54% 7 year follow up there was no difference in survival This trial has shown the non-inferiority of carboplatin to radiotherapy in the treatment of stage I seminoma  fewer second primary testicular germ-cell tumours favour carboplatin use,

34. Pooled analysis of Phase II studies to compare 1 vs 2 cycles Carboplatin Relapse Rate 1 cycle – 4.4% 2 cycles – 2.9% No deaths due to seminoma Prognosis was excellent with either approach No effect on overall survival

35. Paraaortic failures were the most common site So surveillance imaging is required

36. Adjuvant radiotherapy Relapse rates were between 1% and 5% disease specific survival of 100%

37. OPTIMAL DOSE

38. Conclusion - compared with 30 Gy given in 15 fractions during 3 weeks, 20 Gy given in 10 fractions during 2 weeks produces excellent results, with less inconvenience to the patient in terms of the numbers of hospital visits and severity of adverse effects, allowing a speedier resumption of normal living median follow up 61 months

39. 30-Gy 20-Gy Relapse 10 11 5yr RR 3% 3.6% Toxicity Less

40. Optimal planning target volume

41. RT PA and pelvic PA 5year Relapse rates 3.4% 4% Site Supra diaphragmatic Pelvic (1.6%)

42. Paraaortic field resulted in reduced toxicity Diarrhea 7% vs 14% (p=0.013) Leukopenia (p<0.00001) Grade I – 14% vs 29% Grade II – 5% vs 12% Grade III Nausea/Emesis ( p=0.08) Time to normal sperm count improved with PA field despite more testicular shielding in DL group

43. Contraindication Horseshoe kidney Inflammatory bowel disease Prior RT Recurrences most frequently occured within the first 2 to 3 years Local recurrence in - field is rare Biopsy to rule out a nonseminomatous tumor or another malignant tumor Supradiaphragmatic relapse, chemotherapy results in virtually 100% cure rate Isolated inguinal relapse may be treated successfully with RT alone

44. STAGE IIA / IIB Seminoma is exquisitely sensitive to both chemotherapy and radiation RT to retroperitoneum with a boost to involved nodes is the standard for disease with a node <3cm The fields including the landing zone and proximal ipsilateral iliac lymph nodes (dog-field) RT is curative in 80% to 90% of pts, with recurrence largely due to occult disease outside the radiation field Chemotherapy reserved for salvage of patients who subsequently relapse

45. Between April 1991 and March 1994 94 patients , median follow up of 70 months relapse-free survival at 6 years was 95.3% for stage IIA and 88.9 % for stage IIB Conclusion :  Radiotherapy for stages IIA/B seminoma with reduced portals yields excellent tumor control at a low rate of acute toxicity and no late toxicity, which supports the role of radiotherapy as the first treatment choice for these patients.

46. prospective observational study To assess the long-term efficacy and toxicity of front-line cisplatin -based chemotherapy in patients with stage IIA or IIB testicular seminoma. Between April 1994 and March 2003, 72 patients were included

47. 5-year progression-free survival rates for patients with stage IIA or IIB disease were 100% and 87% (95% CI, 77.5% to 97%), respectively. Five-year progression-free and overall survival rates for the whole group were 90% (95% CI, 82% to 98%) and 95% (95% CI, 89% to 100%), respectively chemotherapy is a highly effective and well-tolerated treatment for patients with stage IIA or IIB seminoma that yields excellent progression-free and overall survival rates These results indicate that chemotherapy is an available alternative to radiotherapy in the treatment of these patients and could avoid some of the serious late effects associated with radiotherapy

48. For pts with bulky (>3cm transverse dimension) RP nodes , primary treatment with cisplatin based chemo is standard followed by RT for consolidation to a residual mass >3cm.

49. Despite the statistical equivalence between the two modalities across the CSs and treatment patterns, a difference in the trend of relapses was observed favoring the use of CT in CSIIB. This information, together with the observed (confirmed) incidence of late toxicities and second cancers after RT, actually provides a valuable proof of principle for the use BEP/EP CT as the preferred choice for all stage II cases.

50. Stage IIC &III GOOD PROGNOSIS Survival of 90% to 95% Chemotherapy – BEP X 3 CYCLES OR EP X 4CYCLES INTERMEDIATE PROGNOSIS Overall survival of 75% with standard therapy Chemotherapy – BEP X 4 CYCLES OR VIP X 4 CYCLES

51. Follow up

52. M anagement of residual mass Pts with high tumor burden have one or more sites of residual disease after chemo Management of residual disease is critical to the curative management Dependent on size of residual disease. Residual mass is common due to fibrotic reaction that occur in the treated LN PET CT is taken 6 weeks post chemotherapy Residual mass ≤ 3cm and has a normal serum marker – surveillance

53. Radiotherapy techniques Used for Stage I, IIA and IIB Linear accelerators with >6 MV photon The mean dose ( Dmean ) and dose delivered to 50% of the volume (D50%) of  the kidneys, liver, and bowel are lower with CT-based AP-PA 3D-CRT than  IMRT As a result the risk of second cancers arising in the kidneys , liver or bowel may be lower with 3DCRT than IMRT , hence IMRT is not recommended

54. Simulation Supine CT scan of the abdomen + iv contrast Arms by side Head rest, ankle and knee support Midline and lateral tattoos Scrotal Shield

55. Stage IA,IB 20Gy/10# , 5#s / week in 2 weeks Radiate the PA strip alone with AP-PA field Include the iliac and inguinal nodes and previous scar if h/o pelvic /scrotal surgery in past Include left renal hilum in left sided primaries

56. Borders Superior- junction of T11-T12 Inferior- junction of L5-S1 Lateral- include tips of transverse process Kidney shield to be used D50% </= 8 Gy for both kidneys D15%</= 20 Gy in solitary kidney Vessels can be contoured and 1-2 cms margins around it define CTV and 0.5 cm forms the PTV

57. Stage IIA,IIB 2 phases of treatment using AP-PA without break Modified dog leg -20Gy/10 # Cone down -10Gy/5# in IIA and 16Gy/8# in IIB

58. Modified dog leg(hockey stick) field Treated to 20 Gy/10# at 2Gy /# Covers PA strip, common iliac, external iliac and proximal internal iliac up to acetabulum Stage II A and II B Stage I seminoma with history of scrotal violation, prior inguinal or scrotal surgeries or history of distorted lymphatics

59. Borders Superior- junction of T11-T12 Inferior- roof of I/L acetabulum Medial border- tip of transverse process till L5 and then from C/L transverse process of L5 to medial border of I/L obturator foramen Lateral- tip of transverse process till L5 and then a line from tip of transverse process of I/L L5 to superolateral acetabular border

60. Cone down phase The nodal mass with a 2 cms margin is contoured and the same treated to 30Gy and 36Gy for IIA and IIB respectively at 2Gy/#

61. Toxicities of RT Acute Nausea Vomiting Fatigue Long term Peptic ulceration Risk of 2 nd malignancies Reduced fertility Temporary aspermia - 20 cGy - 50 cGy – recovery at 1 year (only 50% reach their baseline) Permanent aspermia - > 50 cGy Median time to normal post treatment sperm count was 13 months(PA) to 20 months (PA +Pelvic) At 3 years, there was no significant difference