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GERM CELL TUMOURS OF THE TESTIS UROLOGY UNIT UNTH 8/8/07
Case Summary By Dr. S. N. Okeke
Biodata Name: Mr. A.P Age: 36yrs Sex: Male Marital Status: Single Occupation: Civil servant Address: Delta State
Presenting Complaint Recurrent 速 inguinal mass x 10 months.
HPC Was seen at SOP on 15/03/07 with the above complaint Born with absent 速 testis in the hemiscrotum. Associated small lump in the 速 groin. He never sought medical attention till 4yrs prior to presentation when the lump started increasing in size.
Contd 2yrs later he had 速 groin exploration. No histology was done. The surgical wound healed satisfactorily. However 10months after surgery, a new growth appeared at the surgical site. The growth increased in size. Became painful 2wks afterwards, with radiation to the lower back. No trauma to the lump. No pain in any other part of the body.
Contd There was no obvious change in the size of the contralateral well descended testis. No abdominal swelling. No chronic cough. He had lost about 10kg in the preceding 3months. No change in bowel habit. No urinary symptoms
The rest of the history was not contributory.
On Examination Young man. No obvious distress. Afebrile. Not pale. Anicteric. No peripheral lymph adenopathy. No pedal oedema. Vital signs: stable Chest: Clear.
Abdomen Flat. Moved with respiration. A surgical scar at the 速 groin An ovoid mass was deep to the scar. 4x4cm. Hard. Non tender. With definite margins. Not attached to skin. Not attached to underlying muscle. DRE: Essentially normal
Ext. Genitalia Hypoplastic 速 hemiscrotum Absent 速 testis. Well developed undescended left testis of adequate volume. No hypospadias. No chordee
Diagnosis Recurrent 速 testicular tumour in an undescended testis
Investigations FBC. S/E/U/C: normal CXR-PA view: normal Abdominopelvic u/s scan: -Retroperitoneal masses,the largest, about the size of his kidney 7x5cm -Ectopic (pelvic) 速 kidney CT scan: Not done AFP & Beta-hCG: normal
On 23/04/07 He had excision biopsy of the 速 groin mass. Histology: Seminoma Classic variant Diagnosis: seminoma (classic variant) stage IIB (at least)
He was worked up for Cytotoxic therapy by the oncology unit. One week ago, he had 1st course of : IV Cisplatin 20mg/sqm (35mg). for 5days. Tab Etoposide 120mg/sqm (200mg) for 5days. He had no untoward effects. Next course is to follow in 3weeks. He is to have a total of 6 courses. After the complete dose of chemoRx, he will be reassessed for residual disease. Radiotherapy is to follow. Thank you.
SURGICAL ANATOMY OF THE TESTIS BY Dr Okezie Mbadiwe
Ovoid,firm,intrascrotal 5 by 2.5 by 2.5cm 20g Tunica albuginea Tunica vaginalis Epididymis
COVERINGS OF THE TESTIS
Blood supply: Testicular aa Minimal Anastomosis with Ductal and Cremasteric aa Venous Drainage Panpiniform plexus Left testicular vein: Lt. Renal vein Right testicular: IVC Lymphatic drainage Para-aortic nodes (L2) Connections with mediastinal and Cervical nodes Nerve: Sympathetic (T10)
STRUCTURE T. Albuginea Mediastinum testis 200 300 lobules Each lobule: 1 4 tubules (Semniferous tubules) Rete testis Supporting cells (sertoli) Interstitial cells (Leydig)
DESCENT OF THE TESTIS Genital ridge: Germ cells from yolk sac Gubernaculum testis Processus vaginalis
THANK YOU
PATHOLOGY BY DR. I.I. NNABUGWU
INTRODUCTION Testicular cancer is the most common malignancy in young men 15-35yrs. One of the most curable solid neoplasms applying multimodal therapy of malignancies. Germ cells: Pluripotent Germ cell tumours: constitute 90-95% of all primary testicular cancers.
Epidemiology Incidence: 3.7/100,000 American Whites 0.9/100,000 American Blacks 0.1/100,000 Nigeria. Magoha (1995) Age: 0-10yrs: mainly yolksac tumours 20-40yrs: mainly seminoma Race: scandinavian countries, USA & UK, Africa &Asia Genetics: No obvious genetic abnormality identified yet. Right tumours slightly more than left tumours Bilaterality: 2-3% of cases Similar or different histology Simultaneously or successively.
Classification. 6 major attempts since 1940. WHO (1998) classification: Precursor lesions: Ca. in situ Tumours of one histologic type (pure form) 1.Seminoma. 2.Embryonal Ca 3.Yolk sac tumour 4.Polyembryoma 5.Trophoblastic tumours 6.Teratoma: Mature teratoma, Dermoid cyst, Immature teratoma,teratocarcinoma Mixed tumours
Clinical Classification Seminoma Non seminoma
Seminomas Classic: 82-85% of seminoma, Spermatocytic: 2-12% Anaplastic: 5-10% Age range: 20-40yrs Rare in adolescents and infants 5-10% produce beta-hCH(syncytiotrophoblast) Commonest histology in Undescended testis
Yolk sac Tumour Most common testis tumour of infants Produces AFP a.k.a endodermal sinus tumour Adenocarcinoma of infantile testis
Predisposing Factors Undescended testis: may be due to -Gonadal dysgenesis -Abnormal Germ cell morphology -Endocrine dysfunction -Elevated temperature -Impaired blood supply Increased risk of cancer (3-14X general population)
Contd 7-10% of testicular GCT occur in undescent. 5-10% of patients with undescent develop cancer in contralateral well descended testis. Orchidopexy does not prevent carcinogenesis Ectopic testis is not a predisposing condition.
Other Predisposing Conditions Trauma Atrophy Hormone administration (e.g) DES and pregnancy
Natural History All germ cell tumours are malignant or potentially so. Following malignant transformation -CIS -Invasive Ca -Lymphatic spread -Haematogenous spread Spread is predictable except for chorioCa.
Contd Rapid growth with (doubling time 10-30days for NSGCT) Bleeding or Necrosis Spontaneous regression is extremely rare if ever.
Biochemical substances secreted AFP: Yolksac tumour, Embryonal Ca, Teratocarcinoma. Beta-hCG: ChorioCa, Embryonal Ca Lactate Dehydrogenase (LDH) Placental Alkaline phosphatase Human chorionic somatomammotropin.
Staging TNMS According to AJCC &UICC pTis: Intratubular ca. in situ pTo: No tumour identified pTx: Tumour cannot be assessed pT1: Lim. to testis/epid. No vasc/lymph. involv. pT2: Lim. To testis/epid. Vasc./lymph. involv. Or invading tunica vaginalis pT3: Invades spermatic cord +/- vasc/lym. invas. pT4: Scrotal invas. +/- vasc./lymph. invas.
Nodal status Nx: Cannot be assessed N0: No regional lymph node N1: Single or multiple nodes 2cm or less. N2: Single or mult. nodes >2cm & <(=)5cm N3: Node(s) > 5cm.
Distant mets. M0: No evidence M1: Non regional nodal or Pulm. Mets. M2: Non pulm. visceral mets.
Serum Tumour Markers LDH hCG(mIU/ml) AFP(ng/ml) S0 N/< N/< N/< S1 <1.5xN <5000 <1000 S2 1.5-10xN 5000-50,000 1000-10,000 S3 >10xN >50,000 >10,000
Staging Contd Clinically: stage O: pTIS stage I: Confined to scrotum stage II: Regional lymph node. stage III: Distant metastasis
Prognostic factors Tumour burden Number of metastatic sites Level of tumour markers hCG, AFP & LDH
Conclusion Thank you
CLINICAL FEATURES & INVESTIGATIONS BY DR. A.D. OKOH
CLINICAL FEATURES SUBDIVISIONS 1. Incidental dx 2. Hormonal manifestations 3. Localized dx 4. Metastatic dx
INCIDENTAL DX Asymptomatic Discovered during inv. for other reasons e.g. infertility, undescended testis FXS OF HORMONAL MANIFESTATIONS A. SYMPTOMS Breast enlargement effect of tumour hCG secretion B. SIGN Gynaecomastia
FXS OF LOCALIZED DX A. SYMPTOMS Scrotal/Testicular swelling : usu. painless; occ. painful B. SIGNS Testicular mass Consistency Homogenous - Seminoma Inhomogenous - NSGCT Non-tender usu. Intra-scrotal Hydrocele associated wth it occ.
FEATURES OF METASTATIC DX A. SYMPTOMS Loss of appetite (anorexia) Weakness (anaemia) Wt. loss (asthenia) Yellowness of eyes (jaundice) Bone pain/swelling & bone # (spontaneous/trauma) Abd. pain & swelling Cough , chest pain , SOB
B. SIGNS LYMPHADENOPATHY Left supraclavicular Inguinal CHEST Fxs of pleural effusion & pulmonary pathologies ABD Hepatomegaly & ascites Para-aortic LNE MSK Bone swellings & tenderness , # evidence CNS Cerebral mets - Altered consciousness Spinal mets - motor & sensory system dysfxn
INVESTIGATIONS To : Assist in diagnosis Check for complications & stage the dx Plan tx modalities IMAGING STUDIES Testicular USS Abd/pelvic USS CXR
Skeletal survey Radioisotope bone scan CT Scan/MRI Brain Chest Abdomen Scrotal PET
TUMOUR MARKERS Alpha-fetoprotein Beta subunit hCG Lactate dehydrogenase Placental ALP (PLAP) Gamma glutamyl transpeptidase (GGT) OTHERS FBC + ESR SEUCr LFT Mantoux test
DIFFERENTIAL DIAGNOSIS Epididymitis Hydrocele Non-Hodgkin lymphoma Spermatocele Testicular torsion Varicocele
TREATMENT BY DR. B.S. MAKAMA
OUTLINE Factors determining tx modalities Modalities of tx Tx of CIS of the testis Fertility in pxs wth GCT Basis of sensitivity of GCT to DNA damaging agents Conclusion
TX OF GCT OF THE TESTIS Tx depends on the ff factors : Histological type of the tumour Seminoma GCT Non-seminomatous GCT Stage of the dx TNM Boden & Gibb Memorial Sloan-Kettering Cancer Centre Royal Masden Hospital Clinical Low stage dx (T1 - T3 & N1 - N2) Advanced stage dx (T4/N3/M1)
Prediction of metastatic potential (MP) A. NSGCT Vascular/lymphatic invasion Extent of primary tumour (T-stage) Embryonal Ca : 30 40 % of tumour vol. Absence of yolk sac tumour N/B : Low risk metastatic potential - Surveillance High risk metastatic potential - Option of either : RPLND or Chemotherapy
B. Seminomas Predictors of MP for lower stage SGCT Tumour size Vascular & lymphatic invasion Elevated Beta hCG Prognostic staging for metastatic GCT Good prognosis Intermediate prognosis Poor prognosis
TREATMENT Multimodal approach Platinium based chemotherapy Impt. implications of predictable pathways of LN drainage 30 40 % of pxs wth stage 1 NSGCT have occult metastasis MODALITIES OF TX Surgery Radical Inguinal orchidectomy +/- RPLND
Adjuvant Radiotherapy (RT) Adjuvant Chemotherapy SURGERY Radical orchidectomy : including clinically advanced dx POST-RADICAL ORCHIDECTOMY TX MODALITIES : Surveillance RPLND RT Chemotherapy
SURVEILLANCE PRINCIPLES IN STAGE 1TC Strong commitment of both pt & physician Various protocols have been developed : 1st yr Pt seen @ mthly intervals 2nd yr Pt seen @ 2 mthly intervals 3rd yr Pt seen @ 3 mthly interval
Years 4 to 7 Pt seen @ 6 mthly intervals for : O/E CT Scan abdomen/pelvis CXR Tumour markers
SURVEILLANCE OF STAGE 1 SEMINOMA Post-tx options are : RT Surveillance Adjuvant RT remains current tx of choice Surveillance/RT ~ 100% cure in stage 1 seminoma post-orchidectomy irrespective of approach SURVEILLANCE OF STAGE 1 NSGCT Ultimate survival appears less c.f. RPLND Despite this either is advocated
Surveillance appropriate for : Clinical stage 1 wthout relapse risk factor Surveillance protocol motivated pts Pts understanding risk of non- compliance to follow- up schedule
ADJUVANT TX POST-RAD. ING. ORCHIDECTOMY RPLND RPLND I : Confined to pts wth only clinically stage I dx confirmed intra-op Surgical Technique Template
Nerve sparing Survival ~ 100% Relapse outside retroperitoneum Salvaged by chemotherapy
RPLND II Stage IIA or IIB dx Clinically demonstrable or Visible @ surgery Relapse usu. Outside peritoneum LAPAROSCOPIC RPLND : Currently only for staging RPLND III Resection of residual dx Indicated in pts who failed primary tx Performed both for Seminoma & NSGCT
ADJUVANT RT SEMINOMA Low Stage RT std adjuvant tx Sensitive to low dose radiation 2,500 - 3,500 cGy Given over 3 wks To peri-aortic + ipsilat. Inguino-pelvic LN 95% five yr survival Advanced Stage Sometimes used for residual dx after chemotx
Advanced Stage Combination chemotherapy BVP proved effective ~ 90% dx free in 4 yrs NSGCT Low Stage N/B : Primary chemotherapy Survival for 2 cycles of BEP ~ 95 100% No randomised studies against RPLND Long term effects on young adults unclear
NSGCT Higher doses (4,000 5,000 cGy) Long term morbidity N/B: NSGCT are sensitive to chemotherapy Falling out of favour as 1st line tx ADJUVANT CHEMOTHERAPY SEMINOMA Low Stage Efficacy comparable to adjuvant RT, wth single agent Carboplatin Pt quality of life same May gain wider acceptance in the future
CHRONIC TOXICITY 6 categories : Nephrotoxicity Cisplatin CVS Bleomycin +/- Vinblastine Raynauds phenomenom Occlusive vasc. dx Neurotoxicity Cisplatin + Vinblastine Chronic periph. neuropathy Impaired auditory fxn
Pulmonary Bleomycin Pneumonitis Pulmonary fibrosis Second malignancy : Both 2nd GCT + Non-GCT Fertility Oligospermia Azoospermia N/B : Adjuvant chemotherapy can also be used in low stage dx
Advanced Stage A. Good Risk Pt TX GOALS Maintain high cure rates Reduce tx related toxicity Generally receive 4 cycles of EP or 3 cycles of BEP N/B : Bleomycin is essential in good risk if only 3 cycles of chemotx are given 80 - 90% dx free rates
B. Poor Risk Pt 5 yr survival 48% Recently high dose chemotx wth autologous bone marrow transplant (ABMT) or Peripheral stem cell support 4 cycles of BEP + 2 cycles of Etoposide + Carboplatin + ABMT
SALVAGE FOR RELAPSED TC SALVAGE CHEMOTHERAPY Current std is wth Ifosfamide based regimen as 1st line e.g. VIP, BEPI PROGNOSTIC FACTORS FOR SALVAGE CHEMOTX Favourable Prior complete response to Cisplatin based regimen Testis as primary site Unfavourable Initial incomplete response to Cisplatin based regimen Primary mediastinal site
SALVAGE SURGERY Aggressive surgery may offer a reasonable alternative SALVAGE RT RT + high dose chemotherapeutic regimens wth ABMT
TX OF CIS OF THE TESTIS CIS progresses to invasive dx TX OPTIONS Orchidectomy RT Chemotx Observation N/B : Low dose radiation is currently being investigated FERTILITY IN PTS WTH TESTIS CA Young adult men affected, hence fertility a concern Defective spermatogenesis in 25% of pts @ presentation
50% hypofertile post- orchidectomy prior to adjuvant tx Adjuvant tx further impairs fertility 50% returns to normal sperm count @ 2yrs ff chemotx 25% remain azoospermic
Only 35% achieve paternity ff chemotx 76% paternity ff RPLND I Cryo-preservation of semen b/4 chemotx Assisted reproductive techniques (ART) e.g. ICSI
BASIS OF SENSITIVITY OF TC TO DNA - DAMAGING AGENTS When equivalent freq. of strand breaks are produced the testicular cell lines die more readily Damaged DNA leads to increase P53 P53 increase transcription of Waf-1 & Mdm-2 protein Waf-1 a potent inhibitor of cyclin- dependent kinase which causes cell cycle arrest @ G1
Over-expressed myc, myb or EZF, and elevated P53 may lead to apoptosis GCT cells have higher levels of apoptosis promoting proteins - Bax and lower levels of suppressor of apoptosis Bcl 2 Bax:Bcl-2 ratio determines response to cell damage for either apoptosis or repair ? P53 up-regulates Bax & down-regulates Bcl-2
PREVENTION People should be encouraged to do regular self-examination of the testis esp. in the high risk group Monitor tumour markers for testicular tumour
CONCLUSION At present there are a no. challenges facing physicians responsible for the care of pts wth GCT Ongoing devt. in the field of molecular biology are likely to enhance our understanding of the aetiology & pathogenesis of GCT in the future, and hopefully the prevention of these fascinating tumours in the new millenium
THANK YOU & GOD BLESS !

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GERM CELL TUMOURS OF THE TESTIS by Nwabueze.ppt

  • 1. GERM CELL TUMOURS OF THE TESTIS UROLOGY UNIT UNTH 8/8/07
  • 2. Case Summary By Dr. S. N. Okeke
  • 3. Biodata Name: Mr. A.P Age: 36yrs Sex: Male Marital Status: Single Occupation: Civil servant Address: Delta State
  • 4. Presenting Complaint Recurrent 速 inguinal mass x 10 months.
  • 5. HPC Was seen at SOP on 15/03/07 with the above complaint Born with absent 速 testis in the hemiscrotum. Associated small lump in the 速 groin. He never sought medical attention till 4yrs prior to presentation when the lump started increasing in size.
  • 6. Contd 2yrs later he had 速 groin exploration. No histology was done. The surgical wound healed satisfactorily. However 10months after surgery, a new growth appeared at the surgical site. The growth increased in size. Became painful 2wks afterwards, with radiation to the lower back. No trauma to the lump. No pain in any other part of the body.
  • 7. Contd There was no obvious change in the size of the contralateral well descended testis. No abdominal swelling. No chronic cough. He had lost about 10kg in the preceding 3months. No change in bowel habit. No urinary symptoms
  • 8. The rest of the history was not contributory.
  • 9. On Examination Young man. No obvious distress. Afebrile. Not pale. Anicteric. No peripheral lymph adenopathy. No pedal oedema. Vital signs: stable Chest: Clear.
  • 10. Abdomen Flat. Moved with respiration. A surgical scar at the 速 groin An ovoid mass was deep to the scar. 4x4cm. Hard. Non tender. With definite margins. Not attached to skin. Not attached to underlying muscle. DRE: Essentially normal
  • 11. Ext. Genitalia Hypoplastic 速 hemiscrotum Absent 速 testis. Well developed undescended left testis of adequate volume. No hypospadias. No chordee
  • 12. Diagnosis Recurrent 速 testicular tumour in an undescended testis
  • 13. Investigations FBC. S/E/U/C: normal CXR-PA view: normal Abdominopelvic u/s scan: -Retroperitoneal masses,the largest, about the size of his kidney 7x5cm -Ectopic (pelvic) 速 kidney CT scan: Not done AFP & Beta-hCG: normal
  • 14. On 23/04/07 He had excision biopsy of the 速 groin mass. Histology: Seminoma Classic variant Diagnosis: seminoma (classic variant) stage IIB (at least)
  • 15. He was worked up for Cytotoxic therapy by the oncology unit. One week ago, he had 1st course of : IV Cisplatin 20mg/sqm (35mg). for 5days. Tab Etoposide 120mg/sqm (200mg) for 5days. He had no untoward effects. Next course is to follow in 3weeks. He is to have a total of 6 courses. After the complete dose of chemoRx, he will be reassessed for residual disease. Radiotherapy is to follow. Thank you.
  • 17. Ovoid,firm,intrascrotal 5 by 2.5 by 2.5cm 20g Tunica albuginea Tunica vaginalis Epididymis
  • 19. Blood supply: Testicular aa Minimal Anastomosis with Ductal and Cremasteric aa Venous Drainage Panpiniform plexus Left testicular vein: Lt. Renal vein Right testicular: IVC Lymphatic drainage Para-aortic nodes (L2) Connections with mediastinal and Cervical nodes Nerve: Sympathetic (T10)
  • 20. STRUCTURE T. Albuginea Mediastinum testis 200 300 lobules Each lobule: 1 4 tubules (Semniferous tubules) Rete testis Supporting cells (sertoli) Interstitial cells (Leydig)
  • 21. DESCENT OF THE TESTIS Genital ridge: Germ cells from yolk sac Gubernaculum testis Processus vaginalis
  • 24. INTRODUCTION Testicular cancer is the most common malignancy in young men 15-35yrs. One of the most curable solid neoplasms applying multimodal therapy of malignancies. Germ cells: Pluripotent Germ cell tumours: constitute 90-95% of all primary testicular cancers.
  • 25. Epidemiology Incidence: 3.7/100,000 American Whites 0.9/100,000 American Blacks 0.1/100,000 Nigeria. Magoha (1995) Age: 0-10yrs: mainly yolksac tumours 20-40yrs: mainly seminoma Race: scandinavian countries, USA & UK, Africa &Asia Genetics: No obvious genetic abnormality identified yet. Right tumours slightly more than left tumours Bilaterality: 2-3% of cases Similar or different histology Simultaneously or successively.
  • 26. Classification. 6 major attempts since 1940. WHO (1998) classification: Precursor lesions: Ca. in situ Tumours of one histologic type (pure form) 1.Seminoma. 2.Embryonal Ca 3.Yolk sac tumour 4.Polyembryoma 5.Trophoblastic tumours 6.Teratoma: Mature teratoma, Dermoid cyst, Immature teratoma,teratocarcinoma Mixed tumours
  • 28. Seminomas Classic: 82-85% of seminoma, Spermatocytic: 2-12% Anaplastic: 5-10% Age range: 20-40yrs Rare in adolescents and infants 5-10% produce beta-hCH(syncytiotrophoblast) Commonest histology in Undescended testis
  • 29. Yolk sac Tumour Most common testis tumour of infants Produces AFP a.k.a endodermal sinus tumour Adenocarcinoma of infantile testis
  • 30. Predisposing Factors Undescended testis: may be due to -Gonadal dysgenesis -Abnormal Germ cell morphology -Endocrine dysfunction -Elevated temperature -Impaired blood supply Increased risk of cancer (3-14X general population)
  • 31. Contd 7-10% of testicular GCT occur in undescent. 5-10% of patients with undescent develop cancer in contralateral well descended testis. Orchidopexy does not prevent carcinogenesis Ectopic testis is not a predisposing condition.
  • 32. Other Predisposing Conditions Trauma Atrophy Hormone administration (e.g) DES and pregnancy
  • 33. Natural History All germ cell tumours are malignant or potentially so. Following malignant transformation -CIS -Invasive Ca -Lymphatic spread -Haematogenous spread Spread is predictable except for chorioCa.
  • 34. Contd Rapid growth with (doubling time 10-30days for NSGCT) Bleeding or Necrosis Spontaneous regression is extremely rare if ever.
  • 35. Biochemical substances secreted AFP: Yolksac tumour, Embryonal Ca, Teratocarcinoma. Beta-hCG: ChorioCa, Embryonal Ca Lactate Dehydrogenase (LDH) Placental Alkaline phosphatase Human chorionic somatomammotropin.
  • 36. Staging TNMS According to AJCC &UICC pTis: Intratubular ca. in situ pTo: No tumour identified pTx: Tumour cannot be assessed pT1: Lim. to testis/epid. No vasc/lymph. involv. pT2: Lim. To testis/epid. Vasc./lymph. involv. Or invading tunica vaginalis pT3: Invades spermatic cord +/- vasc/lym. invas. pT4: Scrotal invas. +/- vasc./lymph. invas.
  • 37. Nodal status Nx: Cannot be assessed N0: No regional lymph node N1: Single or multiple nodes 2cm or less. N2: Single or mult. nodes >2cm & <(=)5cm N3: Node(s) > 5cm.
  • 38. Distant mets. M0: No evidence M1: Non regional nodal or Pulm. Mets. M2: Non pulm. visceral mets.
  • 39. Serum Tumour Markers LDH hCG(mIU/ml) AFP(ng/ml) S0 N/< N/< N/< S1 <1.5xN <5000 <1000 S2 1.5-10xN 5000-50,000 1000-10,000 S3 >10xN >50,000 >10,000
  • 40. Staging Contd Clinically: stage O: pTIS stage I: Confined to scrotum stage II: Regional lymph node. stage III: Distant metastasis
  • 41. Prognostic factors Tumour burden Number of metastatic sites Level of tumour markers hCG, AFP & LDH
  • 44. CLINICAL FEATURES SUBDIVISIONS 1. Incidental dx 2. Hormonal manifestations 3. Localized dx 4. Metastatic dx
  • 45. INCIDENTAL DX Asymptomatic Discovered during inv. for other reasons e.g. infertility, undescended testis FXS OF HORMONAL MANIFESTATIONS A. SYMPTOMS Breast enlargement effect of tumour hCG secretion B. SIGN Gynaecomastia
  • 46. FXS OF LOCALIZED DX A. SYMPTOMS Scrotal/Testicular swelling : usu. painless; occ. painful B. SIGNS Testicular mass Consistency Homogenous - Seminoma Inhomogenous - NSGCT Non-tender usu. Intra-scrotal Hydrocele associated wth it occ.
  • 47. FEATURES OF METASTATIC DX A. SYMPTOMS Loss of appetite (anorexia) Weakness (anaemia) Wt. loss (asthenia) Yellowness of eyes (jaundice) Bone pain/swelling & bone # (spontaneous/trauma) Abd. pain & swelling Cough , chest pain , SOB
  • 48. B. SIGNS LYMPHADENOPATHY Left supraclavicular Inguinal CHEST Fxs of pleural effusion & pulmonary pathologies ABD Hepatomegaly & ascites Para-aortic LNE MSK Bone swellings & tenderness , # evidence CNS Cerebral mets - Altered consciousness Spinal mets - motor & sensory system dysfxn
  • 49. INVESTIGATIONS To : Assist in diagnosis Check for complications & stage the dx Plan tx modalities IMAGING STUDIES Testicular USS Abd/pelvic USS CXR
  • 50. Skeletal survey Radioisotope bone scan CT Scan/MRI Brain Chest Abdomen Scrotal PET
  • 51. TUMOUR MARKERS Alpha-fetoprotein Beta subunit hCG Lactate dehydrogenase Placental ALP (PLAP) Gamma glutamyl transpeptidase (GGT) OTHERS FBC + ESR SEUCr LFT Mantoux test
  • 54. OUTLINE Factors determining tx modalities Modalities of tx Tx of CIS of the testis Fertility in pxs wth GCT Basis of sensitivity of GCT to DNA damaging agents Conclusion
  • 55. TX OF GCT OF THE TESTIS Tx depends on the ff factors : Histological type of the tumour Seminoma GCT Non-seminomatous GCT Stage of the dx TNM Boden & Gibb Memorial Sloan-Kettering Cancer Centre Royal Masden Hospital Clinical Low stage dx (T1 - T3 & N1 - N2) Advanced stage dx (T4/N3/M1)
  • 56. Prediction of metastatic potential (MP) A. NSGCT Vascular/lymphatic invasion Extent of primary tumour (T-stage) Embryonal Ca : 30 40 % of tumour vol. Absence of yolk sac tumour N/B : Low risk metastatic potential - Surveillance High risk metastatic potential - Option of either : RPLND or Chemotherapy
  • 57. B. Seminomas Predictors of MP for lower stage SGCT Tumour size Vascular & lymphatic invasion Elevated Beta hCG Prognostic staging for metastatic GCT Good prognosis Intermediate prognosis Poor prognosis
  • 58. TREATMENT Multimodal approach Platinium based chemotherapy Impt. implications of predictable pathways of LN drainage 30 40 % of pxs wth stage 1 NSGCT have occult metastasis MODALITIES OF TX Surgery Radical Inguinal orchidectomy +/- RPLND
  • 59. Adjuvant Radiotherapy (RT) Adjuvant Chemotherapy SURGERY Radical orchidectomy : including clinically advanced dx POST-RADICAL ORCHIDECTOMY TX MODALITIES : Surveillance RPLND RT Chemotherapy
  • 60. SURVEILLANCE PRINCIPLES IN STAGE 1TC Strong commitment of both pt & physician Various protocols have been developed : 1st yr Pt seen @ mthly intervals 2nd yr Pt seen @ 2 mthly intervals 3rd yr Pt seen @ 3 mthly interval
  • 61. Years 4 to 7 Pt seen @ 6 mthly intervals for : O/E CT Scan abdomen/pelvis CXR Tumour markers
  • 62. SURVEILLANCE OF STAGE 1 SEMINOMA Post-tx options are : RT Surveillance Adjuvant RT remains current tx of choice Surveillance/RT ~ 100% cure in stage 1 seminoma post-orchidectomy irrespective of approach SURVEILLANCE OF STAGE 1 NSGCT Ultimate survival appears less c.f. RPLND Despite this either is advocated
  • 63. Surveillance appropriate for : Clinical stage 1 wthout relapse risk factor Surveillance protocol motivated pts Pts understanding risk of non- compliance to follow- up schedule
  • 64. ADJUVANT TX POST-RAD. ING. ORCHIDECTOMY RPLND RPLND I : Confined to pts wth only clinically stage I dx confirmed intra-op Surgical Technique Template
  • 65. Nerve sparing Survival ~ 100% Relapse outside retroperitoneum Salvaged by chemotherapy
  • 66. RPLND II Stage IIA or IIB dx Clinically demonstrable or Visible @ surgery Relapse usu. Outside peritoneum LAPAROSCOPIC RPLND : Currently only for staging RPLND III Resection of residual dx Indicated in pts who failed primary tx Performed both for Seminoma & NSGCT
  • 67. ADJUVANT RT SEMINOMA Low Stage RT std adjuvant tx Sensitive to low dose radiation 2,500 - 3,500 cGy Given over 3 wks To peri-aortic + ipsilat. Inguino-pelvic LN 95% five yr survival Advanced Stage Sometimes used for residual dx after chemotx
  • 68. Advanced Stage Combination chemotherapy BVP proved effective ~ 90% dx free in 4 yrs NSGCT Low Stage N/B : Primary chemotherapy Survival for 2 cycles of BEP ~ 95 100% No randomised studies against RPLND Long term effects on young adults unclear
  • 69. NSGCT Higher doses (4,000 5,000 cGy) Long term morbidity N/B: NSGCT are sensitive to chemotherapy Falling out of favour as 1st line tx ADJUVANT CHEMOTHERAPY SEMINOMA Low Stage Efficacy comparable to adjuvant RT, wth single agent Carboplatin Pt quality of life same May gain wider acceptance in the future
  • 70. CHRONIC TOXICITY 6 categories : Nephrotoxicity Cisplatin CVS Bleomycin +/- Vinblastine Raynauds phenomenom Occlusive vasc. dx Neurotoxicity Cisplatin + Vinblastine Chronic periph. neuropathy Impaired auditory fxn
  • 71. Pulmonary Bleomycin Pneumonitis Pulmonary fibrosis Second malignancy : Both 2nd GCT + Non-GCT Fertility Oligospermia Azoospermia N/B : Adjuvant chemotherapy can also be used in low stage dx
  • 72. Advanced Stage A. Good Risk Pt TX GOALS Maintain high cure rates Reduce tx related toxicity Generally receive 4 cycles of EP or 3 cycles of BEP N/B : Bleomycin is essential in good risk if only 3 cycles of chemotx are given 80 - 90% dx free rates
  • 73. B. Poor Risk Pt 5 yr survival 48% Recently high dose chemotx wth autologous bone marrow transplant (ABMT) or Peripheral stem cell support 4 cycles of BEP + 2 cycles of Etoposide + Carboplatin + ABMT
  • 74. SALVAGE FOR RELAPSED TC SALVAGE CHEMOTHERAPY Current std is wth Ifosfamide based regimen as 1st line e.g. VIP, BEPI PROGNOSTIC FACTORS FOR SALVAGE CHEMOTX Favourable Prior complete response to Cisplatin based regimen Testis as primary site Unfavourable Initial incomplete response to Cisplatin based regimen Primary mediastinal site
  • 75. SALVAGE SURGERY Aggressive surgery may offer a reasonable alternative SALVAGE RT RT + high dose chemotherapeutic regimens wth ABMT
  • 76. TX OF CIS OF THE TESTIS CIS progresses to invasive dx TX OPTIONS Orchidectomy RT Chemotx Observation N/B : Low dose radiation is currently being investigated FERTILITY IN PTS WTH TESTIS CA Young adult men affected, hence fertility a concern Defective spermatogenesis in 25% of pts @ presentation
  • 77. 50% hypofertile post- orchidectomy prior to adjuvant tx Adjuvant tx further impairs fertility 50% returns to normal sperm count @ 2yrs ff chemotx 25% remain azoospermic
  • 78. Only 35% achieve paternity ff chemotx 76% paternity ff RPLND I Cryo-preservation of semen b/4 chemotx Assisted reproductive techniques (ART) e.g. ICSI
  • 79. BASIS OF SENSITIVITY OF TC TO DNA - DAMAGING AGENTS When equivalent freq. of strand breaks are produced the testicular cell lines die more readily Damaged DNA leads to increase P53 P53 increase transcription of Waf-1 & Mdm-2 protein Waf-1 a potent inhibitor of cyclin- dependent kinase which causes cell cycle arrest @ G1
  • 80. Over-expressed myc, myb or EZF, and elevated P53 may lead to apoptosis GCT cells have higher levels of apoptosis promoting proteins - Bax and lower levels of suppressor of apoptosis Bcl 2 Bax:Bcl-2 ratio determines response to cell damage for either apoptosis or repair ? P53 up-regulates Bax & down-regulates Bcl-2
  • 81. PREVENTION People should be encouraged to do regular self-examination of the testis esp. in the high risk group Monitor tumour markers for testicular tumour
  • 82. CONCLUSION At present there are a no. challenges facing physicians responsible for the care of pts wth GCT Ongoing devt. in the field of molecular biology are likely to enhance our understanding of the aetiology & pathogenesis of GCT in the future, and hopefully the prevention of these fascinating tumours in the new millenium
  • 83. THANK YOU & GOD BLESS !