Management of Testicular Cancer
Hassan G. TAAN
Urology Resident
AUBMC
Moderator: Prof. Rami Nasr
• Testicular cancer :1% male neoplasms , 5% urological tumours, incidence 310 /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.
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proper staging
chemotherapeutic combinations
early treatment-based radiotherapy and surgery
strict follow-up & salvage therapies
STAGING Of TESTICULAR CANCER
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
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
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
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Nonseminomatous Germ Cell Tumors
Embryonal cell carcinoma
Yolk sac tumor
Teratoma
Choriocarcinoma
Mixed Tumors
Intratubular germ cell neoplasia (CIS)
• 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%
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
STAGE I SEMINOMA
• The overall CSS rate under surveillance : 97-100% 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 20-24 Gy), will reduce the relapse rate to 1-3%
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
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)
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
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
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
Follow Up - Seminoma
Relapses
• Surveillance/Radiotherapy
– BEP x 3
• Chemotherapy cohort
– VIP x 4 (vinblastine, ifosfamide and cisplatin) or
– TIP x 4 (paclitaxol, ifosfamide and cisplatin)
Prognostic factors for occult metastatic disease
in testicular cancer
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
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.
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 largevolume 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
Follow Up – Surveillance Stage I NSGCT
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 longterm 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
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
• 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
• 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
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
PS – pathologic stage,PD – progressive disease, NC – no change