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Testicular cancer
- 2. GCT 95% of testicular cancer are germ cell tumors, either seminoma or non-seminoma Most common age at diagnosis Seminoma :30-35yrs Non- Seminoma : 20-30yrs Most dramatic reduction in mortality occurred in 1970s with the introduction of cisplatin based chemotherapy
- 3. RISK FACTOR History of undescended testes increased risk of malignancy in the normally descended contralateral testes Male infertility is associated with an increased risk of testicular cancer, familial predisposition
- 4. CLASSIFICATION IGCN Seminoma Classic type Spermatocytic type Non seminomatous GCT Embryonal carcinoma Yolk sac (Endodermal sinus) tumor Teratoma Mature Immature With malignant transformation Choriocarcinoma Mixed germ cell tumor Sex cord Stromal Tumors Leydig Cell Tumor SertoIi cell tumor Granulosa cell tumours Fibroma – thecoma stromal tumor Gonadoblastoma Unclassified
- 5. CLASSIFICATION Germ cell Tumors derived from Germ cell Neoplasia in situ Germ cell neoplasia in Situ Seminoma Seminoma with syncytiotrophoblast cells Nonseminomatous germ cell tumors Embryonal carcinoma Yolk sac tumor, post pubertal type Teratoma, post pubertal type Teratomas with somatic type malignancy Trophoblastic tumors Mixed germ cell tumor Regressed germ cell tumor GCT unrelated to germ cell neoplasia in situ Spermatocytic tumor Yolk sac tumor, pre_pubertal type Teratomas, prepubertal type Mixed teratomas and yolk sac tumor, prepubertal type Sex Cord- Stromal tumors
- 6. SEMINOMA CLASSIC TYPE >50% of GCT HCG is elevated in 15-30% of men Related to presence of synctiotrophoblast AFP is not elevated in pure seminoma > 90% will stain positive for PLAP
- 7. SEMINOMA Spermatocytic type 2% of testicular tumor Mean age: 54years Natural history and treatment is different from seminona Confined to testes cured by orchidectomy Metastases is rare Cell of origin is unknown Does not contain glycogen Stains negative for PLAP
- 8. NONSEMINOMATOUS GCT Embryonal cancer is the most common type AFP positive -33% HCG positive -20% Yolk sac tumors High levels of AFP Most common germ cell tumors Teratomas Not Associated with raised AFP/HCG Considered malignant with ability to metastasize Choriocarcinoma Least common type Aggressive Almost always metastasize at diagnosis High levels of HCG
- 9. Primary lymphatic drainage of testes is to retroperitoneal LNs. Scrotum drains directly into inguinal & external iliac LN LEFT TESTICLE drains into RIGHT Pre – aortic, para aortic (around L Renal hilum) → Inter aorto caval nodes Contralateral spread is rare 1st nodes - precaval or interaortocaval Contralateral spread is high
- 10. Seminoma has an orderly & predictable pattern of spread Loco regional lymphatics are the first site of metastatic disease From retroperitoneal → mediastinal → Supraclavicular Haematogenous mets are rare in pure seminoma, but more common in NSGCT
- 11. CLINICAL PRESENTATION and DIAGNOSTIC WORKUP
- 12. CLINICAL PRESENTATION Usually presents as painless swelling in scrotum May present with pain, heaviness and tenderness Retroperitoneal LN , involvement causes back pain, abdominal swelling Gynecomastia – rare ppt of embryonal cancer Occasionally patients present with metastatic germ cell malignancy diagnosed by biopsy or elevated levels of serum tumor markers without evidence of a palpable mass in testes.
- 13. DIAGNOSTIC WORKUP – History Inguinal or scrotal surgery Cryptorchidism, Rectractile testes Orchidopexy
- 14. DIAGNOSTIC WORKUP – Physical Examination Site of LN metastases Gynecomastia Contralateral tester should be examined clinically & by USG
- 15. DIAGNOSTIC WORKUP – Lab CBC LDH AFP – any elevation connotes non seminomatous disease B-HCG PFT, RFT should be performed for patients who may receive bleomycin
- 16. DIAGNOSTIC WORKUP If testicular tumor is suspected, testicular ultrasound should be performed USG helps define the origin of scrotal mass as the vast majority are benign Testicular tumors appear as a solid mass within the testes, often with associated microlithiasis CXR for all patients and CT Chest for all patients with NSGCT of testes should be routinely done FDG-PET role Where CT is questionable Evaluating residual
- 17. DIAGNOSTIC WORKUP - CT CT has limited ability to exclude presence of disease in nodes, Usually size criteria is used >1 cm threshold : sensitivity of 40% & specificity of 95% 7-8 mm threshold : higher accuracy Either threshold shows considerable overlap between normal & abnormal LN Central necrosis & rounded shape are more suspicious
- 18. DIAGNOSTIC WORKUP - MRI Brain MRI is indicated for choriocarcinoma MRI appears equivalent to CT in determining retroperitoneal adenopathy Done in patients in whom iodinated contrast is C/I
- 19. STAGING
- 20. Regional Lymph Nodes Interaortocaval Paraaortic (periaortic) Paracaval Preaortic Precaval Retroaortic Retrocaval
- 21. Changes in 2018 T staging In pure seminoma, T1 is subclassified into Tia & T1b according to Tumor’s size using 3cm cutoff T Epididymal invasion is considered T2 rather than T1 T Hilar soft tissue invasion is T2 M Discontinuous involvement of spermatic cord by vascular lymphatic invasion is M 1
- 22. TNM staging for male germ cell tumors incorporates serum tumor marker elevation as a separate category [S] Cancer of testes is highly curable, even in cases with advanced metastatic disease Stage IV is not included Highest stage is IIIC
- 23. IGCCC
- 24. T STAGING
- 25. N STAGING CLINICAL PATHOLOGICAL Nx Regional LN cannot be assessed N0 No Regional LN mets N1 A lymph node mass <= 2cm Multiple lymph nodes <= 2 cm A LN mode mass <=2cm <= 5 nodes N2 A LN mass >2cm but <= 5cm Multiple LN A LN mass > 2cm <= 5 Cm > 5 nodes positive N 3 > 5cm >5 cm
- 26. S STAGING S Category LDH HCG MIU/mL AFP ng/ml S0 WNL S1 < 1:5 N and < 5000 and < 1,000 S2 < 10 X N OR 5000_50000 1,000-10,000 S3 >1O x N >50,000 > 10,000
- 27. MANAGEMENT
- 28. GENERAL MANAGEMENT Obtaining LDH, AFP, BHCG measurement Radical (inguinal) orchiectomy with division of spermatic cord at internal inguinal ring Involved testis is removed en bloc with spermatic cord, enclosed by tunica layers through an inguinal incision, minimizing the chance of tumor spillage. Scrotal violation is associated with a slight increase in local recurrence rate , with no difference in distant recurrence rate or overall survival
- 29. GERM CELL NEOPLASIA IN SITU
- 30. SEMINOMA STAGE I Cured by orchiectomy alone 20% will relapse if no adjuvant therapy is offered. Either adjuvant RT or chemo with single agent Chemo is asso with DFS> 95% and Disease specific survival ~ 100% Surveillance with treatment at relapse, is associated with a similar Survival outcome
- 31. SURVEILLANCE Every 4to 6 months in the first 2years 6 monthly assessment in years 3-5 Annual assessment untill year 10 Assessment should include physical examination, CT, serum markers More costly approach than adjuvant nodal irradiation but less overall treatment burden Preferred option for compliant patient
- 32. ADJUVANT RT In the past, standard postoperative management has been adjuvant RT to para-oaortic & ipsilateral pelvic nodes DOG-LEG or HOCKEY STICK RT field Dose: 20 Gy Risk of 2ndmalignant neoplasm (SMN)
- 33. ADJUVANT CHEMOTHERAPY Less toxic approach Single agent Carboplatin x 2# Recurrence following adjuvant carboplatin tends to be in retroperitoneum Follow up CT scans are mandatory Can be salvaged with cisplatin based chemo No reported evidence of 2nd malignancy Fewer c/l germ cell neoplasms compared to RT
- 34. From 1994 to 1999, 203 patients with stage I seminoma were included Median follow-up was 52 months (range 14-92). Relapses were observed in two (3.3%) patients treated with carboplatin and in 23 patients (16.1%) on surveillance Five-year disease-free survival was 83.5% for patients on surveillance, and 96.6% for those receiving carboplatin Single-agent carboplatin is effective in reducing the relapse rate in patients with high-risk stage I seminoma Aparicio et al Ann Oncol. 2003 Jun;14(6):867-72
- 35. Oliver Et al J Clin Oncol. 2011 Mar 10;29(8):957-62
- 37. SEMINOMA STAGE II Recommended treatment depends on bulk of retroperitoneal nodal disease RT, 25 - 35 Gy , is the RxOC in stage IIA or IIB Radiation of para- aortic & ipsilateral pelvic nodes is a high effective treatment Recurrence rate< 10% DSS ~ 97→100% MC site of relapse following infradiaphragmatic R T is in the supraclavicular fossa or mediastinum No prospective clinical trial comparing RT Vs Chemo Most patents with Stage IIA/IIB can be cured with cisplatin based chemo, greater levels of toxicity are expected compared to RT alone R T is the preferred treatment for non bulky Stage II seminoma
- 38. A greater number of retroperitoneal LN, may suggest an overall greater bulk of disease, indicating a higher likelihood of distant metastasis, suggesting systemic therapy Patient with stage IIC retroperitoneal disease [nodes> 5cm] are managed with systemic chemotherapy Choice of modality is also influenced by size and location of retroperitoneal nodal mass If the mass is centrally located & does not overlie or overlap kidney or lever, 1° RT remains an option If it overlies kidney or liver, then treatment using cisplatin based combination Chemotherapy is preferred Cisplatin /Etoposide [EP] Bleomycin+ EP [BEP]
- 39. For nodal disease> 10cm, relapse rate with RT >40%, and should be managed with systemic therapy For rare patient with stage III disease [supradiaphragmatic nodal disease or dissemination to parenchymal organs) , or those with relapse following RT, current standard therapy is 3# BEP Or 4# EP These patients are classified into prognostic groups based in IGCCCGG
- 40. RESIDUAL MASS For patients with Stage II or III disease treated with primary Chemotherapy, residual masses are present at 1 month in upto 80% Observation alone is adequate for a residual mass <3cm in size Two patterns of response to chemo are evident Residual mass with well defined discrete borders Amenable to surgical resection Mass with indistinct borders merging into Surrounding structures Observation
- 41. RESIDUAL MASS FDG- PET is more reliable in predicting viable disease – should be performed 6weeks after day21 of last chemo cycle For Either seminoma, or NSGCT, a radiographic complete response does not require consolidative treatment The size criterion for absence of residual mass in a site of LN metastases is a transverse dimension less than 1cm Residual mass> 1cm N SGCT – B/L RPLND Residual teratoma requires no further therapy
- 42. BILATERAL TESTICULAR CANCER 5% of cases Bilateral orchiectomy is an effective management strategy Partial orcheictomy <2cm in size PORT-18-20 Gy to residual testicle to eradicate GCNIS May be kept for observation aIone Requires lifelong testosterone replacement
- 43. STAGE I NSGCT Only LVSI has been validated as risk factor For LVSI negative patients, Observation can be done If LWSI positive, preferred treatment is adjuvant Chemo Primary chemotherapy for NSGCT consists of 1# or 2# BEP
- 44. RETROPERITONEAL LN DISSECTION Done in clinical stage I NSGCT to accurately stage the disease & remove all viable disease Mortality < 1% Minor complications : Prolonged ileus, wound infection, lymphocele Major complications: Hemorrhage Ureteral injury Chylous ascites Pulmonary embolus Wound dehiscence Bowel obstruction
- 45. RPLND Long term morbidity – Sympathetic nerve damage → failure of ejaculation Bilateral infrahilar RPLND includes precaval, retrocaval, paracaval, interaortocaval, retroaortic, pre aortic, para- aortic, common iliac LN Nerve- dissection technique identifies and preserves both, sympathetic chain, post ganglionic sympathetic nerves & hypogastric plexus, which are necessary for anterograde ejaculation
- 46. STAGE IS NSGCT Serum tumor markers that do not normalize after radical orchiectomy are evidence of micrometastases Treatment has been 3# BEP or 4# EP
- 47. PATHOLOGIC STAGE II NSGCT AFTER RPLND Adjuvant chemotherapy should be recommended for patients with pN2 or pN3 disease pN2 disease: 2# pN3: full treatment
- 48. CNS METASTASES Patients with Brain mets are curable MRI is appropriate at baseline for Stage II or III disease Mandatory for patient with significantly elevated BHCG, to rule out choriocarinoma Syndrome RT is useful for post chemo consolidation of residual lesions
- 49. CHORIOCARCINOMA SYNDROME Characterized by rapid hematogenous spread Very high serum HCG levels ~ 105to 106miu/m L Testicular mass Diffuse lung mets Involvement of non pulmonary viscera (Brain, liver) Tumor hemorrhage – hemoplaysis, hemoperitoneum, IC bleed Hyperthyroidism – due to high HCG High rate of mortality Clinical condition rapidly stabilizes with chemo Bleomycin is avoided for 1ST course due to high volume pulmonary mets β Blocker during the first course alleviates Symptoms of hyperthyroidism A male patient with testicular or anterior mediastinal mass, serum HCG> 50, 000 MIU/mL, clinical picture of choriocarcinoma syndrome, does not require orchiectomy or biopsy prior to start of treatment Treated as a medical emergency Immediate chemo offers best chance for survival Resection of involved testes should be performed between cycles or at time of RPLND, once patient has stabilized
- 50. MEDIASTINAL NSGCT Extragonadal GCT are the result of arrested migration of germ cells along urogenital ridge M C presentation – anterior Mediastinum mass 4# BEP for patients withgood pulmonary function 4# VIP if Bleomycin is not given Surgical consolidation essential, as mediasternal tumors have high incidence of viable germ cell malignancy, teratomas and transformation to somatic malignancy
- 51. MANAGEMENT OF RECURRENT DISEASE Patients in first relapse after BEP Chemo can be successfully salvaged in successfully salvaged in ~50% cases Conventional Dose Chemo Most effective regimens for first recurrence after BEP is combination with Ifosfamide & cisplatin Eg: TIP [Paclitaxel, ifosfamide, cisplatin] High Dose Chemotherapy and Stem Cell Transplant HDCT-ASCT= High Dose Chemotherapy- Autologous Stem Cell Transplant Considered in patients with recurrence after 2nd line chemo Molecular targeted therapies do not have an established role in Rx of germ cell tumors Residual lesions that persist after chemotherapy should be resected whenever feasible Most NSGCT recurrences are seen within 2 to 3yrs
- 52. THANK YOU
Editor's Notes
- J Clin Oncol. 2011 Mar 10;29(8):957-62.