1. 1 Tumors of testes and Prostate April 08, 2013

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.

3. The Testicles

4. 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

5. CLASSIFICATION I.Primary Neoplasms of Testis A.Germ Cell Tumour B.Non-Germ Cell Tumour II.Secondary Neoplasms III.Paratesticular Tumours

6. Primary tumour 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

7. Primary tumour  B.Nongerminal Neoplasms : (5 to 10%) 1.Specialized gonadal stromal tumor (a)Leydig cell tumor (b)Other gonadal stromal tumor 2.Gonadoblastoma 3.Miscellaneous Neoplasms (a)Adenocarcinoma of the rete testis (b)Mesenchymal neoplasms (c)Carcinoid (d)Adrenal rest “tumor”

8. A.Adenomatoid B.Cystadenoma of Epididymis C.Mesenchymal Neoplasms D.Mesothelioma E.Metastases II. SECONDARY NEOPLASMS OF TESTIS A.Reticuloendothelial Neoplasms B.Metastases III.PARATESTICULAR NEOPLASMS

9. AETIOLOGY OF TESTICULAR TUMOUR 1.Cryptorchidism 2.Carcinoma in situ 3.Trauma 4.Atrophy

10. CRYPTORCHIDISM & TESTICULAR TUMOUR Risk of Carcinoma developing in undescended testis is 14 to 48 times higher the normal expected incidence

11. CRYPTORCHIDISM & TESTICULAR TUMOUR The cause for malignancy are as follows:  Abnormal Germ Cell Morphology  Elevated temperature in abdomen & Inguinal region as opposed to scrotum  Endocrinal disturbances  Gonadal dysgenesis

12. Testicular Seminoma: Microscopy Seminoma cells separated by delicate fibrous stroma

13. Testicular Teratoma: Microscopy

14. CLINICAL FEATURES  Painless Swelling of One Gonad  Dull Ache or Heaviness in Lower Abdomen  10% - Acute Scrotal Pain  10% - Present with Metatstasis - Neck Mass / Cough / Anorexia / Vomiting / Back Ache/ Lower limb swelling  5% - Gynecomastia  Rarely - Infertility

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

16. 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 Requirements for staging

17. Investigation 1.Ultrasound - Hypoechoic area 2.Chest X-Ray - PA and lateral views 3.CT Scan 4.Tumour Markers - AFP -  HCG - LDH - PLAP

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

19. AFP –(Alfafetoprotein) NORMAL VALUE: Below 16 ngm / ml HALF LIFE OF AFP – 5 and 7 days Raised AFP :  Pure embryonal carcinoma  Teratocarcinoma  Yolk sac Tumour  Combined Tumour

20. 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 60% - Embryonal carcinoma 55% - Teratocarcinoma\ 25% - Yolk Cell Tumour 7% - Seminomas

21. ROLE OF TUMOUR MARKERS  Helps in Diagnosis - 80 to 85% of Testicular Tumours have Positive Markers  Most of Non-Seminomas have raised markers  Only 10 to 15% Non-Seminomas have normal marker level  After Orchidectomy if Markers Elevated means Residual Disease or Stage II or III Disease  Elevation of Markers after Lymphadenectomy means a STAGE III Disease

22. ROLE OF TUMOUR MARKERS cont...  Degree of Marker Elevation Appears to be Directly Proportional to Tumour Burden  Markers indicate Histology of Tumour: If AFP elevated in Seminoma - Means Tumour has Non-Seminomatous elements  Negative Tumour Markers becoming positive on follow up usually indicates - Recurrence of Tumour  Markers become Positive earlier than X-Ray studies

23. PRINCIPLES OF TREATMENT  Seminomas - Radio-sensitive. Treated with Radiotherapy.  Non-Seminomas are radio-resistant and best treated by Surgery  Advanced Disease or Metastasis - Responds well to Chemotherapy

24. PROGNOSIS Seminoma Nonseminoma Stage I99% 95% to 99% Stage II 70% to 92%90% Stage III80% to 85%70% to 80%

25. CONCLUSION  Improved Overall Survival of Testicular Tumour due to Better Understanding of the Disease, Tumour Markers and Cis-platinum based Chemotherapy

26. Prostate Cancer Anatomy  Position  Prostate lies below the bladder  Encompasses the prostatic urethra  Surrounded by a capsule  Separated from the rectum  Layer of fascia termed the Denonvilliers aponeurosis  Blood supply  Inferior vesical artery  Derived from the internal iliac artery  Supplies blood to the base of the bladder and prostate  Capsular branches of the inferior vesical artery –Help identify the pelvic plexus »Arising from the S2-4 and T10- 12 nerve roots  Nervous supply  Neurovascular bundle  Lies on either side of the prostate on the rectum  Derived from the pelvic plexus  Important for erectile function. Theodorescu, D., Prostate Cancer: Management of Localized Disease, www.emedicine.com, 2004www.emedicine.com

27. 27 The Prostate  Size & shape of a chestnut  Encircles 1 st part of urethra  3 types of glands  Contribute to semen (milky fluid and enzymes)  PSA measured as indicator of prostate cancer (“prostate specific antigen”)  Fibromuscular stroma

29. Nodular Pyperplasia of Prostate Hyperplasia of fibromascular element

30. Prostate Cancer Pathophysiology  Peripheral zone (PZ)  70% of cancers  Transitional zone (TZ)  20%  Some claim  TZ prostate cancers are relatively nonaggressive  PZ cancers are more aggressive

31. Prostate Cancer  Relevance  Most common malignancy in men  Incidence  Nearly 200,000 new cases per year in U.S.  Mortality  32,000 deaths in the United States each year  Second most common cause of cancer death in men  Morbidity  Single histologic disease  Ranges  From indolent, clinically irrelevant  To virulent, rapidly lethal phenotype.

33. Prostate Cancer  Risk factors  Increasing age  Family history  African-American  Dietary factors Red meat, high fat dairy product Fruits, vegetables, grain  Nutritional factors have protective effect against prostate cancer  Reduced fat intake  Soy protein  Lycopene  Vitamin E  Selenium  Race  Incidence doubled in African Americans compared to white Americans.  Genetics  Common among relatives with early-onset prostate cancer  Susceptibility locus (early onset prostate cancer)  Chromosome 1, band Q24  An abnormality at this locus occurs in less than 10% of prostate cancer patients.

34. Prostate Cancer Epidemiology  Prostate-specific antigen (PSA) assay has affected incidence of prostate cancer  Incidence  Prior to PSA  19,000 new cases / year in US  1993  84,000  1996  300,000  Since 1996  200,000 per year  A number that more closely estimate the true annual incidence of clinically detectable disease Small, E., Cecil Textbook of Medicine, Prostate Cancer, 2004, WB Saunders, an Elsevier imprint

35. Prostate Cancer Epidemiology  Death rate  Declined by about 1% per year since 1990  Greatest decrease in men younger than age 75 years  Men older than 75 years still account for two thirds of all prostate cancer deaths  Due to  Early detection (screening)  or to improved therapy? Small, E., Cecil Textbook of Medicine, Prostate Cancer, 2004, WB Saunders, an Elsevier imprint

36. Prostate Cancer-Morphology

37. Prostate Cancer Pathophysiology  Adenocarcinoma  95% of prostate cancers  Developing in the acini of prostatic ducts  Rare histopathologic types of prostate carcinoma  Occur in approximately 5% of patients  Include  Small cell carcinoma  Mucinous carcinoma  Endometrioid cancer (prostatic ductal carcinoma)  Transitional cell cancer  Squamous cell carcinoma  Basal cell carcinoma  Adenoid cystic carcinoma (basaloid)  Signet-ring cell carcinoma  Neuroendocrine cancer

38. Carcinoma prostate Microacini of malignant cells infiltrating the prostate stroma

39. Nodular Pyperplasia of Prostate Hyperplasia of fibromascular element

40. Prostate Cancer Clinical Manifestations  Early state (organ confined)  Asymptomatic  Locally advanced  Obstructive voiding symptoms  Hesitancy  Intermittent urinary stream  Decreased force of stream  May have growth into the urethra or bladder neck  Hematuria  Hematospermia  Advanced (spread to the regional pelvic lymph nodes)  Edema of the lower extremities  Pelvic and perineal discomfort

41. Prostate Cancer Clinical Manifestations  Metastasis  Most commonly to bone (frequently asymptomatic)  Can cause severe and unremitting pain  Bone metastasis  Can result in pathologic fractures or  Spinal cord compression  Visceral metastases (rare)  Can develop pulmonary, hepatic, pleural, peritoneal, and central nervous system metastases late in the natural history or after hormonal therapies fail.

42. Prostate Cancer Detection and Diagnosis  PSA level  Helpful in asymptomatic patients  > 60% of patients with prostate cancer are asymptomatic  Diagnosis is made solely because of an elevated PSA level  A palpable nodule on digital rectal examination  Next most common clinical presentation  Prompts biopsy  Much less commonly, patients are symptomatic  Advanced disease  Obstructive voiding symptoms  Pelvic or perineal discomfort  Lower extremity edema  Symptomatic bone lesions.

43. Prostate Cancer Detection and Diagnosis  The PSA level  Better sensitivity but a low specificity  Benign prostatic hypertrophy and prostatitis –Cause false-positive PSA elevations  Threshold  Using a PSA threshold of 4ng/mL –70 to 80% of tumors are detected  Positive predictive value for a single PSA level greater than 10ng/mL –> 60% for cancer,  Positive predictive value for a PSA level between 4 and 10ng/mL –Only about 30%. Small, E., Cecil Textbook of Medicine, Prostate Cancer, 2004, WB Saunders, an Elsevier imprint

44. Prostate Cancer Recommendations  PSA screening  Yearly after age 50 w/ 10 year life expectancy  May start at 45 w/ close relative w/ prostate cancer <65  May start at 40 for multiple close relatives w/ prostate cancer <65 Small, E., Cecil Textbook of Medicine, Prostate Cancer, 2004, WB Saunders, an Elsevier imprint

45. Prostate Cancer Detection and Diagnosis  Transrectal ultrasound with biopsies  Indicated when  The PSA level is elevated  An abnormality is noted on digital rectal examination  Type of biopsy  Sextant biopsies (base, midgland, and apex on each side) –Generally obtained  Seminal vesicles are biopsied in high-risk patients Small, E., Cecil Textbook of Medicine, Prostate Cancer, 2004, WB Saunders, an Elsevier imprint

46. Prostate Cancer Detection and Diagnosis  A bone scan  Warranted only  PSA level greater than 10ng/mL  Computed Tomography or magnetic resonance imaging  Abdominal and pelvic CT or MRI is usually unrevealing in patients with a PSA level less than 20ng/mL.. Small, E., Cecil Textbook of Medicine, Prostate Cancer, 2004, WB Saunders, an Elsevier imprint

47. Prostate Cancer Staging  Stage T1  Nonpalpable prostate cancer  Detected only on pathologic examination  Incidentally noted after –Transurethral resection for benign hypertrophy (T1a and T1b) or –On biopsy obtained because of an elevated PSA (T1c-the most common clinical stage at diagnosis)  Stage T2  Palpable tumor  Appears to be confined to the prostatic gland (T2a if one lobe, T2b if two lobes)  Stage T3  Tumor with extension through the prostatic capsule (T2a if focal, T2b if seminal vesicles are involved)  Stage T4  Invasion of adjacent structures  Bladder neck  External urinary sphincter  The rectum  The levator muscles  The pelvic sidewal Small, E., Cecil Textbook of Medicine, Prostate Cancer, 2004, WB Saunders, an Elsevier imprint

48. Prostate Cancer Treatment  Require individualization  Must take into account  Patient's comorbidity  Life expectancy  Likelihood of cure  Personal preferences –Based on an understanding of potential morbidity associated with each treatment  A multidisciplinary approach (recommended) –Integrate »Surgery »Radiation therapy »Androgen deprivation »Behavioral therapy Small, E., Cecil Textbook of Medicine, Prostate Cancer, 2004, WB Saunders, an Elsevier imprint

49. Prostate Cancer Treatment  Surgery  Traditional  Robotic  Radiation  Brachytherapy  External beam  Cryotherapy  Androgen Deprivation  Watchful waiting Small, E., Cecil Textbook of Medicine, Prostate Cancer, 2004, WB Saunders, an Elsevier imprint

50. Thanks for your attention !!!