Management of Testicular Cancer

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Management of Testicular Cancer

• Hassan G. TAAN
• Urology Resident
• AUBMC
• Moderator Prof. Rami Nasr

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• Testicular cancer 1 male neoplasms , 5
  urological tumours, incidence 3-10 /100,000 per
  year in West
• Risk factors cryptorchidism, Klinefelters
  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

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STAGING Of TESTICULAR CANCER
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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

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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
• T1/224 hours
• LDH
• tumour burden

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GERM CELL TUMORS

• Seminoma
• Typical/Classic (82 85 of seminomas)
• Spermatocytic (2 12 of seminomas)extremely
  low metastatic
  potential. Mengt50years
• 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)

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• 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

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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

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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

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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

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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
  (BEP3 or EP4) is an accepted alternative to
  dog-leg radiotherapy for patients with bulky
  (gt3 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)

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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

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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 BEP3 or EP4 chemotherapy
• Complete radiographic responses are reported in
  70 to 90 of patients, and the 5-year overall
  survival is 91
• With BEP4 chemotherapy, the 5-year overall and
  progression-free survival is 79 and 75,
  respectively

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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

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Follow Up - Seminoma
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Relapses

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

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Prognostic factors for occult metastatic disease
in testicular cancer
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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

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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.

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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

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Follow Up Surveillance Stage I NSGCT
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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 gt 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

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Retroperitoneal lymph node dissection

• If RPLND done, 30 have lymph node involvement,
  pathological stage II (PS2) disease . RPLND -gt
  -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

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• The risk of relapse for PS1 patients is lt 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 lt 2,
  including teratoma relapse .
• The risk of retroperitoneal relapse after a
  properly performed nerve-sparing RPLND is very
  low (lt 2), as is the risk of ejaculatory
  disturbance or other significant side-effects

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• 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

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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

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