The surgical and medical management of testicular tumors.pptx

updated The surgical and medical management of testicular tumour
by Urology resident

1. The surgical and medical management of testicular tumors Presenter : Abiy T.(PGY-III ) AAU,department of surgery,Urology division. Nov,2023

2. Contents Introduction Epidemiology Histology classification Clinical presentation Diagnosis Staging Management Surgical management and techniques References

3. Introduction Management of testicular cancer has evolved and it’s one of the great success stories in oncology Advent of cisplatin based chemotherapy majorly changed management but still surgery retains critical role Success is now measured not only by the survival of the patient, but also by least morbidity and treatment burden. Should be managed with MDT, though still Urologist is key element in medical and surgical management

4. Epidemiology In United States. Rare ,1% to 2% of cancers among adult males The most common - among men aged 20 to 40 years 2nd most common - males aged 15 to 19 years next to Leukemia An estimated 9470 new cases -2021 resulting in approximately 440 deaths, the excellent 5-year survival rate (~95%). Eth- Globocan 2020,28 th rank by incidence and 29 th cause of death among solid malignancies in both sexes The incidence of bilateral GCT is approximately 2% Testis tumors are most common between the ages of 15 and 55. Geography Incidence increasing

5. Histology classification Primary Vs secondary Germ cell vs non Germ cell stromal GCT(95%) Gonada l(s GCNIS-derived and non-GCNIS–derived) Seminoma (55%) NSGCT(45%) Embryonal carcinoma (EC), Yolk sac tumor , teratoma, and Choriocarcinoma subtypes, Either alone as pure forms or In combination as mixed GCT with or without seminoma. Extra Gonadal Non GCT Sex cord-stromal tumors , Leyding cell tumors Sertoli cell tumors Gonadoblastoma Lymphoid and hematopoietic tumors , Tumors of the collecting duct and rete testis, Tumors of the testicular adnexa. Adenomatoid tumor Cysteadenoma Mesothelioma Sarcoma

6. Clinical presentation Local mass effect Painless testicular mass-most common presentation Hormone production related Gynecomastia-2% of patients Diminished fertility- Metastic symptoms 10% to 20% of patients. Regional or distant mets - two-thirds of NSGCTs and 15% of pure seminomas Retroperitoneal LN mets Supraclavicular LN mets Pulmonary mets Brain Mets Physical Examination Testicular examination Inguinal Abdomen Chest

7. DDX Epididymo -orchitis, Torsion, Hematoma, Para-testicular neoplasm (benign or malignant). Hernia, Varicocele, or Spermatocele. Physicians must consider the diagnosis of GCT in any male age 15 to 50 years with A firm testis mass, Midline retroperitoneal mass, or Mass in the left supraclavicular fossa.

8. Diagnosis A solid, firm mass within the testis, testicular cancer must be the considered Delay in diagnosis Pt and clinician factors Scrotal ultrasound Radiographic testing, Measurement of serum tumor markers, Radical inguinal orchiectomy, Retroperitoneal lymph node dissection (RPLND).

9. Radical Inguinal Orchiectomy For histologic evaluation and local tumor control Patients suspected of having a testicular neoplasm Trans scrotal orchiectomy or biopsy is C/I Should be performed within 1/2 weeks Curative in 80% to 85% CS I seminoma 70% to 80% of CS I NSGCT, Evaluation of specimen by experienced pathologists is recommended Testis-Sparing Surgery Highly controversial No role in normal contralateral testis Can be considered in Organ confined tumors Synchronous bilateral tumors Solitary testis Benign or indeterminate lesion Intraoperative frozen section analysis Biopsy of adjacent parenchyma Adjuvant radiotherapy for GCNIS + ve

10. ?contralateral testicular biopsy Retroperitoneal Lymph node dissection Cryopreservation of sperm Baseline semen analysis and sperm banking

11. Scrotal ultrasound Extension of physical examination Typical GCT is hypoechoic NSGCT - heterogeneous Seminoma - homogeneous Bilateral exam Advanced GCT with normal exam Spe about 70% Small <10mm Active surveillance Less radical surgery

12. Tumor markers Help in initial dx but main utility for follow up Done after 4 weeks of orchiectomy Alpha-fetoprotein (AFP) Half life = 5 – 7 days Normal = 10 - 15 µg/L Yolk sac tumors and EC 50% to 70% of low-stage (CS I, IIA, IIB) NSGCTs 60% to 80% of advanced (CS IIC, III) NSGCTs Human chorionic gonadotropin (HCG) half-life = 24 to 36 hours Normal - < 5 to 10 IU/L Choriocarcinoma and EC 40–60% of NSGCT and 10-20% of seminomas Lactate dehydrogenase (LDH) Tumor burden ∝ LDH levels Half-life of LDH is 24 hours. 20% of low-stage GCT 20% to 60% of advanced GCT. Its main use is in the prognostic assessment of GCT at diagnosis.

13. Staging Imaging studies GCT follows a predictable pattern of metastatic spread Except CC (hematogenous) , the most common route of disease dissemination is via lymphatic channels Primary site --> Retroperitoneum--> Distant site RP is the initial site of metastatic spread in 70% to 80% of patients with GCT. 'Landing zone' Rt testis tumors to IAC-->PC--->PA nodes Lt Side to PA ----> IAC nodes Right to left pattern of drainage Retrograde(caudal) spread- distal iliac and inguinal lymph nodes R etrocrural lymph node metastasis --> cisterna chyli --> posterior mediastinum--> lt supraclavicular LN

14. Continued…, CT Abdomen and Pelvis Provides detailed anatomic assessment The retroperitoneum continues to be the most difficult area to accurately stage clinically + ve LN in 10% to 20% of seminomas and 60% to 70% of NSGCT. A size cutoff of 10 mm is frequently used False - ve 63% False + ve 12-40% 5-9mm in 1 ° landing zone MRI is an alternative- For brain mets FDG-PET – post therapy residual mass Chest x-ray Chest CT Post-orchiectomy elevated serum tumor markers Evidence of metastatic disease Abnormal or equivocal findings on chest x-ray (CXR) CS I NSGCT with evidence of LVI or EC predominance Mediastinal or hilar lymphadenopathy in the absence of retroperitoneal disease Biopsy There is no role for routine bone scintigraphy or brain CT imaging at the time of diagnosis

15. Staging Estimate prognosis and guide therapy TNM system combined with serum tumour markers prognostic stage groups from I to III  For advanced disease Prognostic model by the International Germ Cell Cancer Collaborative Group (IGCCCG)

16. AJCC 8 th Ed, staging

17. Summary of staging Stage 0-Tis Stage I-localized disease no LN and normal markers Stage II-regional LNs without distant metastases or marked elevation of serum tumor markers (S0 or S1) A-LN in transverse plane <2cm B - >> b/n 2cm and 5cm C ->> >5cm Stage IS- stage I disease but with persistently elevated markers Stage III A-non regional LNs or pulm mets with S0-S1 B-any lymph node involvement/size/ mets but moderate raised STMs(S2) without distant metastases C –any lymph node involvement/size/ mets but markedly raised STMs(S3)

18. Prognostic Classification of Advanced Germ Cell Tumor Those that have metastasized to retroperitoneal lymph nodes or beyond TNM staging is supplemented with prognostic model NSGCT Seminoma Prevalence 5 year survival(PFS & OAS) Prevalence 5 year survival(PFS & OAS) Good 56% 89-92% 90% 82-86% Intermediate 28% 75-80% 20% 67-72% Poor 16% 41-48% -

19. Management Principles of management Aggressive approach Early treatment Limit double treatment Avoid over/under Rx Shared decision making Management depends on Histology Stage Serum tumor marker level Relapse Residual mass Options of management after Radical orchiectomy Surveillance Primary Chemotherapy Induction chemotherapy First line 2 nd line Salvage chemotherapy Post chemotherapy surgery RT RPLND Post surgery/RPLND management

20. Seminoma NSGCT CS I, II, and III disease at Dx 85%, 10%, and 5% 1/3,1/3,1/3 Occult metastasis among patients with CS I 10-15% 25-35% Systemic relapse after treatment of the retroperitoneum 1-4% after RT 10% after RPLD Serum Markers Not elevated(not included in risk stratification), not used to guide RX Elevated Chemo and RT sensitivity Highly sensitive Less sensitive Teratoma risk at mets sites Less concerning except failed conventional therapy High risk-post chemosurgery

21. Treatment of Germ Cell Neoplasia In Situ GCNIS is a precursor lesion for GCT - 50% risk of developing an invasive GCT within 5 years. GCNIS is diagnosed by testicular biopsy done for The investigation of infertility, Contralateral testis biopsy Within the affected testis in a patient undergoing testis-sparing surgery. The choice of therapy should be individualized based on The patient's desire for Future paternity, To avoid testosterone replacement therapy Contralateral testis status Rx options Radical orchiectomy, Low-dose radiotherapy(>20Gy), and Close observation.

22. Non-seminoma Germ Cell Tumor Clinical stage I Orchiectomy alone cure rate>75% Risk factors for recurrence lymphovascular invasion or Invasion of spermatic cord or scrotum. Predominance of embryonal carcinoma Low risk-none of above-relapse rate-10%-14% Surveillance(preferred) Primary Chemotherapy(expert opinion) RPLND High risk-1 or more of RF-20-40% Primary Chemotherapy- BEP or EP one cycle Vs Two cycle RPLND Surveillance Teratoma with somatic malignant transformation-RPLND

23. Clinical stage II Normal serum markers CS IIA RPLD-preferred Accurately stage disease possibly avoid uncessarynchemo Alternatively First line chemo-   bleomycin ,  etoposide , and  cisplatin  (BEP)/3x or Etoposide and cisplatin (EP) 4x Post chemo RPLND-residual mass Surveillance if staging is ambiguous Strict follow up CS IIB/C Chemotherapy Vs RPLND( RFS-(98 versus 79 percent)) three cycles -BEP , Alternative -4x EP Post chemo RPLND-residual mass Elevated serum markers(CS IIA-C) about 50% relapse-after RPLD Three cycles -BEP , Alternative -4x EP Post chemo RPLND-residual mass

24. Continued Pathological stage II Histology Confirmed LN involvement-done for CS I Pure teratoma – active surveillance after RPLND. Tumors containing elements of embryonal carcinoma, seminoma, yolk sac tumor , and/or choriocarcinoma  Chemotherapy active surveillance Stage pIIA Active surveillance-recurrence about 50% Chemotherapy -1 or 2 cycles of BEP/EP Stage pIIB /C Chemotherapy -3x BEP/4 cycles of Ep Active surveillance Treatment of residual masses RPLND->1cm in long axis <1cm Surveillance-–recurrence about 4% RPLND-if pt opted Special considerations Histologic features LVI and / or Predominance of EC-high relapse with RPLND- chemo Pure teratomas- RPLD preferred -as less sensitive for chemo Relapse Chemo naïve Post chemo Early Late Post salvage chemo relapse-resection Desperation chemo-progressive ds despite 1/2 nd line chemo-poor prognosis Selected pts –resection of mass

25. Summary of Mngt of NSGST

26. CS IIA and IIB NSGCT-RPLND Vs Chemo RPLND (+/- adjuvant chemotherapy) Advantages Disadvantage 13% to 35% of patients have pathologically negative lymph nodes Additional therapy is required in 48% or more of patients About 30% have retroperitoneal teratoma that is resistant to chemotherapy Post RPLND 13% to 15% -require a full induction chemotherapy regimen Long-term cancer-specific survival is 98% to 100% High-quality RPLND may not be deliverable at all institutions 10% to 52% avoid any chemotherapy Ejaculatory dysfunction 10-30% Induction chemotherapy (+/- postchemotherapy RPLND) Advantage Disadvantage 60% to 78% of patients achieve a complete response and avoid post-chemotherapy surgery, long-term toxicity of chemotherapy and Treatment can be delivered at community-based institutions post-chemotherapy RPNLD Cancer specific survival is 96% to 100%

27. Seminoma Stage CSI >85% cure by orchiectomy alone Active surveillance Adjuvant chemotherapy Carboplatin 1 Vs 2 cycle Adjuvant RT Large field-’Dog Leg’ radiation Small field -Paraaortic strip radiation Radiation dose-20Gy in 10 fractions

28. Treatment of stage II seminoma 15% of seminomas Stage IIA seminoma (S0) Borderline lymph nodes (1 cm) Lymph nodes between 1 and 2 cm RT-modified dog leg field Chemo -3xBEP/4EP Stage IIA seminoma (S1) Chemo -3xBEP/4EP Stage IIB seminoma (S1) Chemo -3xBEP/4EP ?Role Of RPLND Stage IIc seminoma (S0/S1) Chemo -3xBEP/4EP

29. Relapsed Seminoma Chemotherapy-Naïve Seminoma Relapse CSI-on surveillance- Primary DL-RT-70-90%cure rate CSI-primary chemo- First line chemo CS I-IIB seminoma treated with primary radiotherapy- First line chemo Incomplete or Partial response or Residual mass Patients with bulky (>3 cm) retroperitoneal masses and systemic relapse First-line chemotherapy -salvage rates approach 100%. First-line chemotherapy cures virtually all patients who relapse outside the retroperitoneum after primary radiotherapy

30. Initial risk-stratified treatment for advanced testicular germ cell tumors GCTs - metastasized to retroperitoneal lymph nodes or beyond Includes: In most cases- stage III or stage IIb to IIc Stage IS non-seminomas -assumed harbour occult micro mets stage IS seminomas -very rare individualized Rx Primary mediastinal or retroperitoneal GCTs ,even in the absence of metastatic lesions. Stage IIa seminoma (if they are not Rx with RT) and Stage IIa non-seminoma (if they are not managed with RPLND).

31. Risk stratification Treatment depends on Risk stratification Histology seminoma versus no seminoma The presence or absence of Metastatic lesions to organs other than the lungs, Serum tumor marker levels The location of the primary tumor Testis or Retroperitoneum versus mediastinum.

32. Treatment options Good risk cisplatin-based combination therapy BEP- 4x vs 3x-preferred EP 4x Preferred in pts increased risk for pulmonary toxicity from bleomycin and for men over the age of 50 Intermediate- and poor-risk advanced disease   BEP-4cycles-standard care  (VIP)  ifosfamide ,  etoposide , and  cisplatin )- Similar rate of PFS and OS Less hematologic toxicity with BEP(73% vs 89%) alternative for pts not BEP candidates

33. Continued…, Monitoring Response Tumor markers on day 1 of each chemotherapy CT of the chest, abdomen, and pelvis should be performed Prior to chemotherapy and At the completion of chemotherapy. A positron emission tomography (PET)/CT is For patients with stage II/III seminoma, indicated six to eight weeks after the completion of chemotherapy if there is a residual mass on CT imaging ≥3 cm. Prognosis Depends on histology and risk Expected five-year survival rate over 95 percent

34. Summary of Advanced GCT management

35. Residual mass-After chemo for Advanced GCT Seminoma Imaging CT-residual mass less than 3 cm surveillance -Spontaneous resolution 50-60%within 12-18mos PET-if CT shows >3cm Surgery- ≥3 cm that are FDG avid  If the PET scan is negative, we suggest surveillance Non Seminoma Normal serum tumor markers >1cm Resection <1cm- close surveillance Stable or elevated tumor markers  close surveillance or resection Relapse after RPLND Salvage chemo

36. Continued…, Role of Metastasectomy Liver mets > 10mm –resection Mediastinal mass Neck disease Lung mets Brain mets Multisite disease Role of adjuvant chemotherapy ff resection of residual mass Favourable prognosis-90 and 92 %OS,DFS Complete resection Less than 10 percent viable tumor cells on final pathology Good risk pts

37. Testicular ca in undescended testis Cryptorchidism-1 % of new borns 40x increased risk than scrotal testes Incidence in UDT varies from 2.23 to 5.4%, Role orchidopexy Staging Dx Hx and P/E Imaging Serum tumor markers Management No treatment guideline Principle is same as scrotal GCT Mangt institution based experience Up front surgery followed by chemotherapy Single step approach First give induction chemo then mass excision and RPLND-avoids relap Prognosis and OS almost same with scrotal GCT

38. Non–Germ Cell Tumors Sex Cord-Stromal Tumors Rare, making -0.4% to 4% of testis neoplasms Leydig cells, Sertoli cells, granulosa cells, or thecal cells Approximately 90% of these tumors are benign and 10% are malignant. Histologic criteria(Benign Vs Malignant) tumor size larger than 5 cm, necrosis, vascular invasion, nuclear atypia, high mitotic index, increased MIB-1 expression, infiltrative margins, extension beyond the testicular parenchyma, and DNA ploidy Most malignant cases are associated with at least 2 of these features. However, the presence of metastatic disease is the only reliable criteria for making this distinction

39. Leydig Cell Tumors Leydig cell tumors account for 75% to 80% of sex cord-stromal tumors . Most of these occur b/n 30 and 60 years-25% in children. No association with cryptorchidism. Sonographic appearance of these tumors is variable and is indistinguishable- from GCT In the presence of gynecomastia, infertility, depressed libido, or precocious puberty, LH, FSH, testosterone, estrogen , and estradiol should also be Rx- Testis-sparing surgery Mets to retroperitoneum and lungs Resistant to chemo and RT Sertoli Cell Tumor These tumors constitute less than 1% of testis neoplasms. Median age-45 Mostly bilateral Rx –same as Leydig cell tumors

40. Secondary Tumors of the Testis Lymphoma Primary testicular (NHL) is a rare tumor -1% to 2% of all cases of lymphoma. Eighty-five percent of cases occur in men over age 60. NHL is the most common testicular neoplasm in men over age 50. Bilateral testicular involvement -35% of cases. Presentation It usually is seen as a painless testicular mass in an older male. Approximately 25% -systemic symptoms (fever, night sweats, weight loss). CNS-involvement at diagnosis in 10% of men. The initial treatment is radical inguinal orchiectomy. Most cases are associated with systemic disease and the overall prognosis is poor.

41. Continued Leukemic Infiltration The testis is a frequent site of relapse in boys with ALL. The majority of boys are in complete remission at the time of testicular enlargement. The diagnosis can usually be made by biopsy, and orchiectomy is unnecessary . Local control can be achieved with low-dose radiotherapy (20 Gy ), and treatment should include the contralateral testis Because of the frequent risk of bilateral involvement. Overall, the prognosis is poor because most have associated systemic disease.

42. Metastases Metastases to the testis are rare. Bilateral involvement occurs in 15% of patients. The most common primary tumors are prostate, lung, melanoma, colon, and kidney cancer. Although treatment is largely dictated by the primary tumor , orchiectomy may be considered for palliative reasons.

43. Follow up Active surveillance Vs follow up after treatment No single follow-up plan is appropriate for all patients Intense follow up for the first two years Depends on histology, Staging, previous Rx Components Hx and P/E Imaging CT of abdomen,pelvis CXR Serum markers Optimal duration of follow up

44. Treatment sequalae Early Orchiectomy hypogonadism RPLND Ejaculatory dysfunction Cisplatin based chemotherapy Fatigue, myelosuppression, infection, peripheral neuropathy, hearing loss, diminished renal function, and death. Impact on spermatogenesis RT Fatigue, nausea and vomiting, leukopenia, and dyspepsia Impact on spermatogenesis Late toxicity Peripheral neuropathy, Raynaud phenomenon, Hearing loss, hypogonadism, Infertility, Secondary malignant neoplasms, Cardiovascular disease

45. Surgical techniques Radical orchiectomy SA or local anesthesia Supine position Transverse 3-5 cm incision over inguinal canal Spare Ilioinguinal Nerve Separate ligation- gonadal vessels and Vas Divided Spermatic cord at the level of internal inguinal ring Non absorbable suture with 1-2 cm suture tail Secure hemostasis close abdomen in layers Sterile dressing and scrotal support

46. Continued…, Partial orchiectomy Polar ,<2cm,absent or compromised contralateral testes Delivery of testes through inguinal incision Locate mass Intraop U/s Palpation Incision Vertical incision along the long axis of the testicle Horizontal incision Mass excision along normal small rim of seminiferous tubules Frozen section from surrounding tissue –show GCT/ITGCN Completion vs Adjuvant RT T.Albugnia - close with absorbable suture Fix at 3 points

47. Continued…, Delayed orchiectomy For pts presented with diffuse mets and or symptomatic pt who requires early chemo Dx by Biopsy from mets sites or clinically For patients with an apparent retroperitoneal/extragonadal primary GCT is more controversial.

48. Retroperitoneal Lymph Node Dissection Testicular cancer -spread to the retroperitoneal lymph nodes in a predictable fashion . Primary RPLND : high-risk clinical stage (CS) 1 NSGCT or Low-volume CS II (N1) NSGCT with normal STMs PC-RPLND : Refers to an RPLND performed after induction chemotherapy. there is a residual mass > 1 cm in the retroperitoneum and the STMs post-chemotherapy are normal. Salvage PC-RPLND : After both induction and salvage chemotherapy Desperation PC-RPLND : After chemotherapy where there is elevated STMs Reoperative RPLND : Performed after a prior RPLND Resection of late relapse : Performed for relapse of disease > 24 months after a complete response from primary chemotherapy

49. Preoperative Planning Review of CT-not older than 6 weeks, STMs within 7 to 10 days. Any anomaly Sperm banking –who desire paternity No Bowel preparation Pulmonary function test –Bleomycin related toxicity-11% only 1.7% with non bleomycin Preoperative chest CT-with prior lung lesions

50. Continued…, Open VS Laparoscopic Staging and therapeutic procedure Goal Minimize complication such as ejaculatory dysfunction Maintain oncologic efficacy Traditional RPLND-bilateral suprahailar / infrahailar Modified Unilateral/bilateral template dissection Modified unilateral template dissection Lesions <3cm pre and post chemo imaging Normal post-chemotherapy STMs IGCCCG good/intermediate risk Bilateral infrahilar RPLND-standard of care for PC_RPLND

51. Surgical technique Supine position Midline incision Thoracoabdominal approach chevron Exposure of the Retroperitoneum

52. Rt side RPLND Split and Roll Technique Left Para-Aortic Packet Gonadal vein Nerve sparing Interaortocaval Packet Right Paracaval Packet Auxiliary Procedures 23-45% PC-RPLND Nephrectomy followed by vascular interventions

53. Complications of RPLND Over all complication 10-24% Infertility/sub fertility Ejaculatory dysfunction(preserved >90% with modified unilateral) Pulmonary complications Lymphocele-1.7% Ileus-21% VTE Chylous ascites-2-7% PC-RPLND Neurogenic complications- position,blulk LN compresing Mortality- Rare in primary <1% in PC-RPLND

54. References Campbell 12thE,2012 Testicular ca management guideline, NCCN 2023 Up To date online Gupta V, Giridhar A, Sharma R, Ahmed SM, Raju KVVN, Rao TS. Malignancy in an Undescended Intra-abdominal Testis: a Single Institution Experience. Indian J Surg Oncol. 2021 Mar;12(1):133-138. doi : 10.1007/s13193-020-01262-9. Epub 2021 Jan 7. PMID: 33814843; PMCID: PMC7960876.

55. Thank You!