1. Gestational Trophoblastic Disease
NOVAK 34.
Gestational Trophoblastic Disease
부산백병원 산부인과
R1 손영실

2. INDEX # Persistent Gestational Trophoblastic Tumor # Chemotherapy
1. Nonmetastatic Disease
2. Metastatic Disease
3. Staging
4. Prognostic Scoring System
5. Diagnostic Evaluation
6. Management of Persistent GTT
# Chemotherapy
1. Single-agent Treatment
2. Combination Chemotherapy

3. # Persistent Gestational Trophoblastic Tumor

4. NONMETASTATIC DISEASE
◎ Locally invasive GTT
: about 15% of patients after molar evacuation and after
other gestations
◎ Symptoms
① irregular vaginal bleeding
② theca lutein cysts
③ uterine subinvolution or asymmetric enlargement
④ persistently elevated serum hCG levels
◎ Histology of persistent GTT
① after molar evacuation ⇒ H-mole or choriocarcinoma
② after nonmolar pregnancy ⇒ always choriocarcinoma

5. METASTATIC DISEASE
• 4% of patients after evacuation of a complete mole
• usually associated with choriocarcinoma
• early vascular invasion with widespread dissemination
• spontaneous bleeding at meatstatic foci
• metastatic site
: lung(80%), vagina(30%), pelvis(20%), liver(10%),
and brain(10%)

6. METASTATIC DISEASE 1. Pulmonary 2. Vaginal
• lung involvement is visible on chest x-ray of 80% of
patients with metastatic GTT
① “snowstorm” pattern
② discrete rounded density
③ pleural effusion
④ an embolic pattern by pulmonary arterial occlusion
• Sx : chest pain, cough, hemoptysis, dyspnea,
or asymptomatic lesion
2. Vaginal
• occurs in 30% of patients with metastatic tumor
• highly vascular, may bleed vigorously if sample is taken
for biopsy
• Sx : irregular bleeding, purulent discharge

7. METASTATIC DISEASE 3. Hepatic 4. CNS • 10% of patients
• Sx : epigastric or RUQ pain
(if metastases stretch the hepatic capsule)
• hemorrhagic → causing hepatic rupture & intraperitoneal
bleeding
4. CNS
• generally seen in patients with advanced disease
• spontaneous bleeding → acute focal neurologic deficits

8. STAGING ◎ Stage Ⅰ ◎ Stage Ⅱ ◎ Stage Ⅲ ◎ Stage Ⅳ
- by FIGO classification
◎ Stage Ⅰ
: patients have persistently elevated hCG levels and tumor
confined to the uterine corpus
◎ Stage Ⅱ
: patients have metastases to the vagina and pelvis or both
◎ Stage Ⅲ
: patients have pulmonary metastases with or without
uterine, vaginal, or pelvic involvement
◎ Stage Ⅳ
: patients have advanced disease and involvement of the
brain, liver, kidneys, or gastrointestinal tract

9. STAGING Stage Ⅰ Disease confined to uterus Stage ⅠA
Disease confined to uterus with no risk factors
Stage ⅠB
Disease confined to uterus with one risk factor
Stage ⅠC
Disease confined to uterus with two risk factors
Stage Ⅱ
Gestational trophoblastic tumor extending outside uterus but limited to genital
structures (adnexa, vagina, broad ligament)
Stage ⅡA
Gestational trophoblastic tumor involving genital structures without risk factors
Stage ⅡB
structures with one risk factor
Stage ⅡC
structures with two risk factors
Stage Ⅲ
Gestational trophoblastic disease extending to lungs with or without known genital
tract involvement
Stage ⅢA
Gestational trophoblastic tumor extending to lungs with or without genital tract
involvement and with no risk factors
Stage ⅢB
involvement and with one risk factor
Stage ⅢC
involvement and with two risk factors
Stage Ⅳ
All other metastatic sites
Stage ⅣA
All other metastatic sites without risk factors
Stage ⅣB
All other metastatic sites with one risk factor
Stage ⅣC
All other metastatic sites with two risk factors

10. PROGNOSTIC SCORING SYSTEM
◎ to consider other variables
to predict the drug resistance
to assist in selecting appropriate chemotherapy
◎ higher than 7
: categorized as high risk requires intensive combination
chemotherapy

11. PROGNOSTIC SCORING SYSTEM
Score 1 2 4
Age (years)
≤39
＞39 -
Antecedent pregnancy
H-mole
Abortion
Term
Interval between end of
antecedent pregnancy and
start of chemotherapy
(months) ＜4
4-6
7-12
＞12
Human chorionic gonadotroin
(IU/liter)
＜103
＞105
ABO groups
O or A
B or AB
Largest tumor, including
uterine (cm) ＜3
3-5 ＞5
Site of metastases
Spleen,
kidney
Gastrointestinal
tract, liver
Brain
Number of metastases
1-3
4-8 ＞8
Prior chemotherapy
1 drug
≥2 drugs

12. DIAGNOSTIC EVALUATION
◎ All patients with persistent GTT should undergo a careful
pretreatment evaluation
① complete history and physical exam
② measurement of serum hCG level
③ hepatic, thyroid, and renal function test
④ determination of baseline peripheral WBC & platelet count
◎ The metastatic workup
① chest radiograph or CT scan
② ultrasonography or CT scan of the abdomen & pelvis
③ CT or MRI scan of the head
◎ When the pelvic exam & chest radiographic findings are
negative, metastatic involvement of other sites is uncommon

13. MANAGEMENT OF PERSISTENT GTT
Stage Ⅰ
Initial
Single-agent chemotherapy or hysterectomy with adjunctive
chemotherapy
Resistant
Combination chemotherapy
Hysterectomy with adjunctive chemotherapy
Local resection
Pelvic infusion
Stage Ⅱ and Ⅲ
Low riska
Single-agent chemotherapy
High riska
Second-line combination chemotherapy
Stage Ⅳ
Brain
Whole-heat irradiation (3,000 cGy)
Craniotomy to manage complications
Liver
Resection to manage complications
Resistanta
Hepatic arterial infusion

14. MANAGEMENT OF PERSISTENT GTT
1. Stage Ⅰ
- the selection of Tx is based primarily on whether the
patients desire to retain fertility
A. Hysterectomy plus Chemotherapy
• If patient does not wish to preserve fertility
⇒ hysterectomy + adjuvant single chemotherapy
• Reasons of adjuvant chemotherapy
① to reduce disseminating viable tumor cells at surgery
② to maintain a cytotoxic level of chemotherapy in case
viable tumor cells are disseminated at surgery
③ to treat any occult metastases that may already be
present at surgery

15. MANAGEMENT OF PERSISTENT GTT
B. Chemotherapy Alone
• In patients with stage Ⅰ who desire to retain fertility
⇒ single-agent chemotherapy
⇒ 92.1% of patients attained complete remission
• Patients are resistant to single-agent chemotherapy
(desire to retain fertility)
⇒ combination chemotherapy
• If resistant to both
⇒ local uterine resection may be considered

16. MANAGEMENT OF PERSISTENT GTT
2. Stage Ⅱ and Ⅲ
- low-risk : single agent chemoTx
- high-risk : combination chemoTx
A. Vaginal and Pelvic Metastasis
• vaginal metastases may bleed profusely
(∵ highly vascular and friable)
⇒ controlled by packing or by wide local excision
B. Pulmonary Metastasis
• persistent viable pulmonary metastasis despite intensive
chemotherapy
⇒ thoracotomy may be attempted to excise the
resistant focus

17. MANAGEMENT OF PERSISTENT GTT
C. Hysterectomy
• may be required in patients with metastases to control
uterine hemorrhage or sepsis
D. Follow-up (Stage Ⅰ ~ Ⅲ)
① weekly measurement of hCG levels until normal
for 3 consecutive weeks
② monthly measurement of hCG values until normal
for 12 consecutive months
③ effective contraception during the entire interval of
hormonal follow-up

18. MANAGEMENT OF PERSISTENT GTT
3. Stage Ⅳ
- primary intensive combination chemotherapy and the
selective use of radiation therapy and surgery
A. Hepatic Metastasis
• resistant to systemic chemotherapy
→ hepatic arterial infusion of chemotherapy
• acute bleeding of tumor
→ hepatic resection

19. MANAGEMENT OF PERSISTENT GTT
B. Cerebral Metastasis
• If diagnosed, whole-brain irradiation (3,000 cGy in 10
fractions) can be instituted promptly
• conurrent use of combination chemotherapy and brain
irradiation
→ spontaneous cerebral hemorrhage ↓
C. Follow-up (Stage Ⅳ)
① weekly determination of hCG levels until they are
normal 3 consecutive weeks
② monthly determination of hCG levels until they are
normal for 24 consecutive months
• increased risk of late recurrence
→ prolonged gonadotropin follow-up is required

20. MANAGEMENT OF PERSISTENT GTT
Evacuation and
weekly hCG titers
GTN
Mole
Metastatic
work-up
↓ hCG
titers
↑ or plateaud
hCG titers
Choriocarcinoma
Distant metastasis
Uterine disease
Careful follow-up
and contraception
Lung metastasis
Single drug
chemotherapy or
hysterectomy
Pelvic metastasis
Calculate
risk
Combination
chemotherapy
± surgery ± RT
Low
High
Follow-up
Resistant
Stage Ⅳ
Stage Ⅰ
Stage Ⅲ
Stage Ⅱ

21. # Chemotherapy

22. SINGLE-AGENT TREATMENT
◎ Nonmetastatic and low-risk GTT
⇒ actinomycin D (Act-D) or MTX has achieved comparable
and excellent remission rates
◎ Protocols
① Act-D can be given every other week as a 5-day regimen
or in a pulsatile fashion
② use of MTX was the same
◎ Methotrexate with folic acid (MTX-FA)
① the preferred single agent in the Tx of GTT
② remission rates
- 90.2% in stage Ⅰ
- 68.2% in low-risk stages Ⅱ & Ⅲ
③ after Tx with MTX-FA, thrombocytopenia, granulocytopenia
and hepatotoxicity developed in only 1.6%, 5.9% and 14.1%
of patients

23. SINGLE-AGENT TREATMENT
1. Technique of Single-agent Treatment
◎ Serum hCG levels is measured weekly after each course of
chemotherapy
◎ hCG regression curve serves as the primary basis for
determining the need for additional Tx
◎ After 1st Tx
① Further chemotherapy is withheld as long as the hCG level
is falling progressively
② Additional single-agent chemotherapy is not administered
at any predetermined or fixed interval
◎ 2nd course of chemotherapy is administered under the
following conditions
① If the hCG level plateaus for more than 3 conseutive weeks
or begins to rise again
② If the hCG level does not decline by 1 log within 18 days
after completion of the first treatment

24. COMBINATION CHEMOTHERAPY
1. Triple Therapy
◎ etoposide, MTX, Act-D, cyclophosphamide
and vincristine (EMA-CO)
- had complete remission in patients with metastasis and a
high-risk score (76~94%)
- remission occurred in 13 of 15 patients (86%) with brain
metastasis
◎ EMA-CO regimen
① the preferred primary Tx in patients with metastasis and a
high-risk prognostic score
② generally well tolerated
③ seldom has to be suspended because of toxicity

25. COMBINATION CHEMOTHERAPY
2. Duration of therapy
◎ Combination chemotherapy should be given as often as
toxicity permits until the patients achieves three
consecutive normal hCG levels
◎ After normal hCG levels are attained, at least two
additional course are administered to reduce the risk
of relapse

26. 감사합니다.