1. Management of Testicular Tumours Dr. Khaled Abulkhair, PhD Medical Oncology SCE, Royal College, UK Ass. Professor of Clinical Oncology Mansoura Faculty of Medicine

2. TESTICULAR TUMOUR  1% of all Malignant Tumour  Affects young adults - 20 to 40 yrs - when Testosterone Fluctuations are maximum  90% to 95% of all Testicular tumours from germ cells  99% of all Testicular Tumours are malignant.  Causes Psychological & Fertility Problems in young

3. ANATOMY

4. Pathogenesis & Natural History of Testicular Tumour  Course of Spread of Germ Cell Tumours are predictable once Histology of Tumour confirmed  Lymphatic Spread has a set pattern depending on side of Tumour.  Rt. Sided tumors to Inter Aorto-Caval L.N, while the Lt. sided to Para Aortic L.Ns.  High Grade Tumours spread by both Vascular invasion & via Lymphatics

5. L.N DRAINAGE

6. Epidemiology Incidence :1.2 per 100,000 (Bombay) 3.7 per 100,000 (USA) Age :3 Peaks - 20-40 yrs. Maximum - 0 - 10 yrs. - After - 60 yrs. Bilaterality : 2 to 3% Testicular Tumour

7. SURVIVAL IN TESTICULAR TUMOURS Improved overall survival in last 15 to 20 years due to - Better understanding of Natural History and Pathogenesis of disease Reliable Tumour Markers Cis-platinum based chemotherapy

8. HISTOLOGIC CLASSIFICATION I. Primary Neoplasma of Testis. A.Germ Cell Tumour B.Non-Germ Cell Tumour II.Secondary Neoplasms. III.Para-testicular Tumours.

9. I. PRIMARY NEOPLASMS OF TESTIS A. Germinal Neoplasms : (90 - 95 %) 1.Seminomas - 40% (a)Classic Typical Seminoma (b)Anaplastic Seminoma (c)Spermatocytic Seminoma 2.Embryonal Carcinoma - 20 - 25% 3.Teratoma - 25 - 35% (a)Mature (b)Immature 4.Choriocarcinoma - 1% 5.Yolk Sac Tumour

10. I. PRIMARY NEOPLASMS OF TESTIS B. Non-germinal Neoplasms : ( 5 to 10% ) 1.Specialized gonadal stromal tumor (a)Leydig cell tumor (b)Sertoli cell tumor (c)Granulosa cell tumor (d)Other gonadal stromal tumor 2.Gonadoblastoma 3.Miscellaneous Neoplasms (a)Adenocarcinoma of the rete testis (b)Mesenchymal neoplasms (c)Carcinoid (d)Adrenal rest “tumor”

11. II. SECONDARY NEOPLASMS OF TESTIS A.Reticuloendothelial Neoplasms (Sanctuary sites) B.Metastases III.PARATESTICULAR NEOPLASMS A.Adenomatoid B. Cystadenoma of Epididymis C.Mesenchymal Neoplasms D.Mesothelioma E.Metastases

12. RISK FACTORS OF TESTICULAR TUMOUR 1. Cryptorchidism… Risk of Carcinoma developing in undescended testis is 14 to 48 times the normal expected incidence 2.Sex chromosome abnormalities: Germ cell tumors occur at a rate of 25% in dysgenetic gonads, intersexes, hermaphrodites & pseudohermaphrodites 3.Carcinoma in situ 4.Trauma 5.Atrophy

13. CRYPTORCHIDISM & TESTICULAR TUMOUR Risk of Carcinoma developing in undescended testis is 14 to 48 times the normal expected incidence. Why? - Abnormal Germ Cell Morphology. - Elevated temperature in abdomen & Inguinal region as opposed to scrotum. - Endocrinal disturbances. - Gonadal dysgenesis

14. Requirements for staging To properly Stage Testicular Tumours following are pre-requisites: (a)Pathology of Tumour Specimen (b)History (c)Clinical Examination (d)Radiological procedure - USG / CT / MRI / Bone Scan (e)Tumour Markers -  HCG, AFP

15. Clinical Staging of Testicular Tumour Staging A or I- Tumour confined to testis. Staging B or II- Spread to Regional nodes. – IIA - Nodes <2 cm in size or < 6 Positive Nodes – IIB - 2 to 5 cm in size or > 6 Positive Nodes – IIC - Large, Bulky, abd. mass usually > 5 to 10 cm – Staging C or III - Spread beyond retroperitoneal nodes or above diaphragm or visceral disease. – NO STAGE IV

16. TNM Staging of Testicular Tumour Remember Lymphatic drainage of the epididymis and scrotal skin is towards the inguinal L.N

17. Continued….

19. CLINICAL PRESENTATIONS Painless Swelling of One Gonad Dull Ache or Heaviness in Lower Abdomen 10% - Acute Scrotal Pain 10% - Present with Metastases - Neck Mass / Mediastinal mass/ Cough / Anorexia / Vomiting / Back Ache/ Lower limb swelling 5% - Gynecomastia Rarely - Infertility

20. WHAT TO DO FOR ANY SOLID SCROTAL SWELLING? All patients with a solid, Firm Intra- testicular Mass that cannot be Trans- illuminated should be regarded as Malignant unless otherwise proven Maintain a high level of suspicion for adult onset hydrocele too. Do Not Do biopsy.. Fatal error

21. Investigations 1.Ultrasound - Hypoechoic area 2.Chest X-Ray - PA and lateral views 3.CT Scan?? Done after tissue diagnosis to accurately assess the stage. 4.Tumour Markers - AFP -  HCG - LDH - PLAP

22. Tumour Markers TWO MAIN CLASSES Onco-fetal Substances : AFP & HCG Cellular Enzymes : LDH & PLAP ( AFP - Trophoblastic Cells ) ( HCG - Syncytiotrophoblastic Cells )

23. AFP –( Alfa-fetoprotein ) NORMAL VALUE: Below 16 ngm / ml HALF LIFE OF AFP 5 - 7 days Raised AFP : Pure embryonal carcinoma Teratocarcinoma Yolk sac Tumour Combined Tumour REMEMBER: AFP Not raised in Pure Choriocarcinoma or Pure Seminoma

24. HCG – ( Human Chorionic Gonadotropin ) Has  and  polypeptide chain NORMAL VALUE: < 1 ng / ml HALF LIFE of HCG: 24 to 36 hours RAISED  HCG 100 % - Choriocarcinoma (hyperthyroidism) 60% - Embryonal carcinoma 55% - Teratocarcinoma 25% - Yolk Cell Tumour 7% - Seminomas (Syncytiotrophoblastic)

25. ROLE OF TUMOUR MARKERS Helps in Diagnosis - 80 to 85% have Positive Markers. Most of Non-Seminomas have raised markers. Post Orchiectomy if Markers Elevated means Residual Disease or Stage II or III Disease Raised Markers after Lymphadenectomy means a STAGE III. Marker Elevation is Directly Proportional to Tumour Burden Markers may indicate Histology of Tumour: If AFP elevated in Seminoma - Means it is NSGCT. Negative Tumour Markers becoming positive on follow up usually indicates - Recurrence of Tumour Markers become Positive earlier than X-Ray studies.

26. PRINCIPLES OF TREATMENT High inguinal orchiectomy is the mainstay of treatment. Treatment should be aimed at one stage above the clinical stage Seminomas - Radio-Sensitive. Non-Seminomas are Radio-Resistant and best treated by Surgery and chemotherapy. Advanced Disease or Metastases - Chemotherapy. Lymphatic spread initially goes to retro-peritoneal nodes. Early hematogenous spread is RARE. Bulky Retroperitoneal Tumours or Metastatic Tumors Initially “down-staged” with chemotherapy.

27. Treatment of pure seminoma IA-IB

28. Treatment of pure seminoma IIA-III

30. Radiation Therapy considerations Stage IA-B.. Doses 20Gy/10 fractions and only to para aortic area T11-L5. Iliac and inguinal L.Ns are not needed to be treated except in those patients with previous pelvic or scrotal surgeries. Stage IIA-IIB.. Doses up to 30 -36Gy by cone down technique.. Dog leg treated to 20 Gy then field size decreased. RT is not an accepted option of treatment if the following conditions exist: - Inflammatory bowel, horse show kidney and prior RT.

31. NSGCT Stage IA-IB

32. NSGCT Stage IIA-IIB

33. NSGCT Stage IIC-III Initial CHEMOTHERAPY followed by SURGERY for Residual Disease and or RPLND or surveillance.

34. STANDARD CHEMOTHERAPY FOR NON-SEMINOMATOUS GERM CELL TUMOURS Chemotherapy Toxicity BEP - BleomycinPulmonary fibrosis Etoposide (VP-16) Myelosuppression Alopecia Renal insufficiency (mild) Secondary leukemia Cis-platinRenal insufficiency Nausea, vomiting Neuropathy

35. CONCLUSION Testicular tumors are Highly curable and every efforts should be made to accurately manage these cases. Post treatment follow up is equally important. Improved Overall Survival of Testicular Tumour due to Better Understanding of the Disease, Tumour Markers and Cis-platinum based Chemotherapy Current Emphasis is on Diminishing overall Morbidity of Various Treatment Modalities.