1. Management of Testicular Cancer
Hassan G. TAAN
Urology Resident
AUBMC
Moderator: Prof. Rami Nasr

2. Germ cell tumors constitutes 95% of testicular tumors
Testicular cancer :1% male neoplasms , 5% urological tumours, incidence /100,000 per year in West
Risk factors : cryptorchidism, Klinefelter’s syndrome, family history, contralateral tumor, and infertility
Germ cell tumors constitutes 95% of testicular tumors
Testicular tumours show excellent cure rates.
proper staging
chemotherapeutic combinations
early treatment-based radiotherapy and surgery
strict follow-up & salvage therapies

3. STAGING Of TESTICULAR CANCER

4. Staging – AJCC (American Joint Comittee on Cancer)
Stage 0 – CIS
Stage I – T1-4/N0/M0
IA – T1
IB – T2-4
IS – ANY T, S1-3
Stage II – T1-4/N1-3/M0
IIA – N1
IIB – N2
IIC – N3
Stage III – T1-4/N1-3/M1

5. Tumour Markers Alpha-fetoprotein Trophoblasts
Major serum binding protein produced by foetal yolk sac, liver, GIT
Negligible amounts after 1 year of age
T1/2 :4-6 days
Beta-human chorionic gonadotrophin
Syncytiotrophoblasts
Secreted by placenta for maintanence of corpus luteum
T1/2:24 hours
LDH
tumour burden

7. GERM CELL TUMORS Seminoma :
Typical/Classic (82 – 85 % of seminomas)
Spermatocytic (2 – 12 % of seminomas)—extremely low metastatic potential. Men>50years
Anaplastic previously classified as separate entity that was believed to be more aggressive/lethal due to greater mitotic activity. However, mitotic index is not associated with worse prognosis, so term no longer used
Nonseminomatous Germ Cell Tumors
Embryonal cell carcinoma
Yolk sac tumor
Teratoma
Choriocarcinoma
Mixed Tumors
Intratubular germ cell neoplasia (CIS)

8. Frequency of Histologic causes:
GCT constitute 90 – 95% of all primary testicular malignancies
Seminoma: 30 – 60%
Embryonal carcinoma: 3- 4 % in pure form (present in 40% of NSGCTs)
Teratoma: 5 – 10%
Pure choriocarcinoma: 1%
Mixed GCTs: 60%

9. PATTERNS OF SPREAD OF GCTs
Right testis :
- Interaortocaval nodes at level of 2nd vertebral body
Left testis :
Left paraaortic and preaortic nodes (bounded by left ureter, left renal vein, aorta and origin of IMA)
Cross-over: Right to left (but NOT left to right)
Epididymis: external iliac chain
Inguinal node mets may occur if:
Scrotal involvement of primary tumor
Prior inguinal or scrotal surgery
Retrograde lymphatic spread from massive retroperitoneal LN deposits

11. STAGE I SEMINOMA
The overall CSS rate under surveillance : % for seminoma stage I .
The drawback of surveillance :intensive follow-up, repeated imaging of the retroperitoneal lymph nodes, for at least 5 years after orchidectomy
There was no significant difference between one cycle of carboplatin compared to adjuvant radiotherapy, with regard to recurrence rate, time to recurrence, and survival after a median follow-up of 4 years
Adjuvant radiotherapy to a para-aortic field or to a hockeystick field , with moderate doses (total Gy), will reduce the relapse rate to 1-3%

12. SURVEILLANCE FOR STAGE I SEMINOMA
H& PE ,serum tumor markers (bhCG, LDH, AFP) every 3-4 months the first year, every 6 months the second year, then annually thereafter
Imaging: Chest radiography each visit; CT scan of the pelvis annually for 3 years if status post para-aortic radiotherapy

13. STAGE IIA-B SEMINOMA
15 to 20 percent of seminoma patients have CS II disease, 70% of whom have CS IIA-B. Dog-leg radiotherapy using 25 to 30 Gy is employed at most centers
Long-term disease-free survival rates are 92% to 100% for CS IIA and 87% to 90% for CS IIB , with in-field recurrences reported in 0% to 2% and 0% to 7% of cases, respectively
Relapses are cured in virtually all cases with first-line chemotherapy, and disease-specific survival approaches 100%
Induction chemotherapy using first-line regimens (BEP×3 or EP×4) is an accepted alternative to dog-leg radiotherapy for patients with bulky (>3 cm) and/or multiple retroperitoneal masses because the risk of relapse is lower than with dog-leg radiotherapy (15% and 30% of CS IIA and IIB patients in one center)

14. Surveillance for stage IIa/b seminoma
H& PE and serum tumor markers every 3-4 months in years 1-3, every 6 months in year 4, and then annually thereafter
Imaging: Radiography each visit; CT scan of the abdomen and pelvis during month 4 of the first year

16. STAGE IIC AND III
Patients with CS IIC and III seminoma are treated with induction chemotherapy
Ninety percent of patients with advanced seminoma are classified as good risk and should receive either BEP×3 or EP×4 chemotherapy
Complete radiographic responses are reported in 70% to 90% of patients, and the 5-year overall survival is 91%
With BEP×4 chemotherapy, the 5-year overall and progression-free survival is 79% and 75%, respectively

17. Surveillance for stage IIc, III seminoma
H& PE and serum tumor markers every 2 months the first year, every 3 months the second year, every 4 months the third year, every 6 months the fourth year, and then annually thereafter
Imaging: Chest radiography each visit; CT scan of the abdomen and pelvis during month 4 of the first year status post surgery (otherwise, every 3 months until stable); PET scan as clinically indicated

18. Follow Up - Seminoma

19. Relapses Surveillance/Radiotherapy Chemotherapy cohort BEP x 3
VIP x 4 (vinblastine, ifosfamide and cisplatin) or
TIP x 4 (paclitaxol, ifosfamide and cisplatin)

20. Prognostic factors for occult metastatic disease in testicular cancer

21. Impact on fertility and fertility-associated issues
In patients in the reproductive age group, pre-treatment fertility
assessment (testosterone, LH and FSH levels) should be performed, and semen analysis and cryopreservation should be offered.
If cryopreservation is desired, it should preferably be performed before orchidectomy, but in any case prior to chemotherapy treatment
In cases of bilateral orchidectomy or low testosterone levels after treatment of TIN, life-long testosterone supplementation is necessary
Patients with unilateral or bilateral orchidectomy should be offered a
testicular prosthesis

22. Non Sminoma Germ Cell Tumors
Approximately one third of NSGCT patients have CS I with normal postorchiectomy levels of serum tumor markers
The optimal management of these patients continues to generate controversy because the long-term survival associated with surveillance, RPLND, and primary chemotherapy approaches 100%
Up to 30% of NSGCT patients with clinical stage I (CS1) disease have subclinical metastases and will relapse if surveillance alone is applied after orchidectomy.

23. ? > 40% embryonal carcinoma a separate risk factor

24. Surveillance In NSGCT CS1
Close surveillance after orchidectomy in CS1 NSGCT patients showed a
cumulative relapse rate of ~30%, with 80% of relapses occurring during the first 12 months of follow-up, 12% during the second year and 6% during the third year, decreasing to 1% during the fourth and fifth years
35% of relapsing patients have normal levels of serum tumour markers
at relapse. 60% of relapses are in the retroperitoneum
Despite very close follow-up, 11% of relapsing patients presented with large-volume recurrent disease.
surveillance within an experienced surveillance programme may be offered to patients with non-risk stratified clinical stage I non-seminoma as long as they are compliant and informed about the expected recurrence rate as well as the salvage treatment

25. Follow Up – Surveillance Stage I NSGCT

26. Primary chemotherapy In NSGCT CS1
Several studies involving two courses of chemotherapy with cisplatin, etoposide and bleomycin (PEB) as primary treatment for high-risk patients (having ~50% risk of relapse) have been reported .
In these series, involving > 200 patients, some with a median follow-up of nearly 8 years , a relapse rate of only 2.7% was reported, with very little long-term toxicity
Two cycles of cisplatin-based adjuvant chemotherapy do not seem to adversely affect fertility or sexual activity
slow-growing retroperitoneal teratomas after primary chemotherapy

27. Retroperitoneal lymph node dissection
If RPLND done, ~30% have lymph node involvement, pathological stage II (PS2) disease . RPLND -> -ve L.N (PS1), ~10% of the PS1 patients relapse at distant sites.
The main predictor of relapse in CS1 NSGCT managed by surveillance, for having PS2 disease and for relapse in PS1 after RPLND- vascular invasion in the primary tumour .
Patients without vascular invasion constitute ~50-70% of the CS1 population, and these patients have only a 15-20% risk of relapse on surveillance, VS 50% relapse rate in patients with vascular invasion

28. The risk of relapse for PS1 patients is < 10% for those without vascular invasion and ~30% for those with vascular invasion
If two (or more) courses of cisplatin-based chemotherapy are given adjuvant to RPLND in PS2 cases, the relapse rate is reduced to < 2%, including teratoma relapse .
The risk of retroperitoneal relapse after a properly performed nerve-sparing RPLND is very low (< 2%), as is the risk of ejaculatory disturbance or other significant side-effects

29. In a randomised comparison of RPLND with one course of PEB chemotherapy, adjuvant chemotherapy significantly increased the 2-year recurrence-free survival to 99.41% as opposed to surgery, which had a 2-year recurrence-free survival of 92.37%
It was also found that one adjuvant PEB reduced the number of recurrences to 3.2% in the high-risk and to 1.4% in the low-risk patients

31. CS1S with (persistently) elevated serum tumour markers
If the marker level increases after orchidectomy, the patient has residual disease. If RPLND is performed, up to 87% of these patients have pathological finding in the nodes .
An U/S of the contralateral testicle must be performed, if this was not done initially.
The treatment of true CS1S patients is still controversial. They may be treated with three courses of primary PEB chemotherapy and with follow-up as for CS1B patients (high risk) after primary chemotherapy, or by RPLND .
The presence of vascular invasion may strengthen the indication for primary
chemotherapy as most CS1S with vascular invasion will need chemotherapy sooner or later

32. PS – pathologic stage,PD – progressive disease, NC – no change