The Role of General Obgyn on

Diagnosis and Management of GTD

Deri Edianto
FK USU / RSUP H. Adam Malik
Medan
Introduction
• GTD : rare tumor can be cured even with widespread metastasis
• Includes: HM, invasive mole, ETT, PSTT and choriocarsinoma
• Arise from fetal tissue
• GTN is term for malignant form
• Commonly follow a molar pregnancy
• May also from abortion, ectopic pregnancy, or term pregnancy
• Secreted hCG and serve as sensitive marker
Gestational Trophoblastic Disease
• Gestational trophoblastic disease (GTD) or neoplasia (GTN) covers a spectrum of
benign and malignant
• Arising from malformed pregnancies
• HM: benign tumor and the majority of GTD (about 80% of GTDs)
• Choriocarcinomas are malignant tumors developing in the uterus from villous
CTB cells
• 50% of choriocarcinomas arise from a complete molar, 25% following a normal
pregnancy, and 25% after a spontaneous miscarriage or ectopic pregnancy
• ETT and PSTT arise from intermediate trophoblast cells of the placental bed after
a full-term pregnancy or a non-molar miscarriage
Schematic of the different karyotypes of complete and partial hydatidiform
moles

F1000Research 2019, 8(F1000 Faculty Rev):428 Last updated: 10 APR 2019 Understanding and management of gestational trophoblastic disease
Fen Ning, Houmei Hou, Abraham N. Morse , Gendie E. Lash
Schematic of the different benign and malignant forms of gestational
trophoblastic diseases

F1000Research 2019, 8(F1000 Faculty Rev):428 Last updated: 10 APR 2019 Understanding and management of gestational trophoblastic disease
Fen Ning, Houmei Hou, Abraham N. Morse , Gendie E. Lash
Diagnosis of GTD
• Ultrasound is the imaging modality of choice
• Allows the detection of HM before the onset of systemic
manifestations
• Secrete hCG which is therefore a sensitive tumor marker
• Glycoprotein hormone produced by trophoblastic tissue
• HM sometimes diagnosed by pathology after D&C for a suspected
early embryonic demise
• Histological confirmation of GTD after evacuation is mandatory
Treatment options for GTD
• Standard treatment depending on the type and stage of disease: D&C, hysterectomy, chemotherapy
or a combination
• In general, D&C is used for HM and retain her fertility
• Careful post-treatment monitoring is required to ensure no recurrence
• Severe and chemoresistant disease and when fertility preservation is not a concern, hysterectomy
is common option, particularly if there are no distant metastases.
• One aspect of the treatment of GTD that is still controversial is prophylactic chemotherapy in HM
who are at high risk of persistence rather than following their hCG levels until they achieve the
criteria for declaring no evidence of disease or meet the definition of persistent GTD
• The Cochrane concluded that prophylactic chemotherapy might reduce the risk of progression to
GTN, but the strength of the conclusion is limited by the poor quality of the studies.
• Another divergence in the treatment of GTD is a second curettage when a patient’s hCG trend is
non-reassuring after initial evacuation of a HM. The classic teaching was that owing to the risk of
life-threatening hemorrhage or uterine perforation (or both), a second D&C should not be
performed
Treatment of HM
• The initial treatment is suction evacuation (preserve fertility) followed by serial hCG monitoring
• Pre-treatment evaluation: serum quantitative βhCG, blood count, clotting studies, renal and liver functions,
blood type, pelvic US examination, chest X-ray and thyroid function test if hyperthyroidism is suspected
• D&C under ultrasound guidance, helps to remove all molar tissue and avoid perforation
• HM diagnosed at early gestational age, complications during or after evacuation are uncommon
• Most common complications: bleeding, perforation, and respiratory distress syndrome.
• Respiratory distress syndrome caused by: trophoblastic embolization, high-output congestive heart failure
caused by anaemia, hyperthyroidism, preeclampsia, or iatrogenic fluid overload
• The evacuated tissues should be inspected and sent for histological examination
• Uterine evacuation by medication only method is not recommended due to high failure rates, risk of
haemorrhage, increased risk of post-molar GTN and increased maternal morbidity
• After evacuation, effective contraception is crucial
Treatment of HM (con’t)
• Hysterectomy with salpingectomy is an alternative method (childbearing is complete)
• Especially > 40 years, because have a higher risk of post molar GTN
• Eliminates the possibility of local myometrial invasion as a source of persistent disease and
reduces the need for subsequent chemotherapy.
• Adnexa may be preserved, even theca lutein cysts are present
• Compared to uterine evacuation, has a significant advantage in preventing post-molar GTN with
an approximately 80% reduction in risk.
• Does not eliminate the possibility of post molar GTN, patients monitored postoperatively with
serial hCG
• Prophylactic chemotherapy reduction in the incidence of post molar GTN to 3%-8%
• Be limited to special situations where adequate hCG follow-up is not possible and the risk of post
molar GTN is much greater than normal
Treatment of HM (con’t)
• hCG level remains elevated after treatment, further treatment is given
in form of chemotherapy or surgery, depending upon the condition
• Before starting chemotherapy, the patient is assessed using the WHO
scoring system
• Scored as low risk (score < 6) or high risk (score >/= 7 and more)
• Low risk: Single-agent therapy with methotrexate and folinic acid
• High risk: Multiagent chemotherapy
• The cure rate for women with a score of 6 or less is almost 100%,
while the rate for women with a score of 7 or greater is 94%
FIGO criteria for diagnosis of postmolar GTN

Advances in diagnostics and management of gestational trophoblastic disease. Nusa Lukinovic1, Eva Pavla Malovrh1, Iztok Takac1,2, Monika Sobocan1,2, Jure Knez1,2
Radiol Oncol 2022; 56(4): 430-439
WHO Prognostic Scoring
Prognostic factor 0 1 2 4
Age (yr) <40 ≥40 - -
Antecedent HM Abortion Term -
pregnancy
Interval (month) <4 4-6 7-12 >12
hCG <10³ 10³- 10⁴ 10⁴ - 10⁵ >10⁵
ABO groups O xA B
(female x male) AxO AB
Largest tumor < 3 cm 3-5 cm >5 cm
(including uterine
tumor)
Site metastasis Lung Spleen, kidney GI tract Brain, Liver
Number 1-4 4-8 >8
metastasis
Prior Single drug Two or more
chemotherapy
Gestational Trophoblastic Neoplasia (GTN)
• GTN: invasive mole, choriocarcinoma, PSTT, ETT
• Also to patient who presented plateauing or increasing hCG
• Recently, atypical placental site nodule (APSN) has been added to the GTN
• Required treatment with chemotharapy
• The reported incidence of GTN after molar pregnancy is 18% to 29%.
• Choriocarcinoma affects approximately 1 in 40.000 pregnancies and 1 in 40 HMs.
• It is 1000 times more likely after a CHM than another pregnancy event.
• 50% of choriocarcinoma cases arise from HMs, 25% follow abortion or tubal
pregnancy and 25% are associated with other gestational events
• PSTT and ETT are rare subtypes of GTN with an incidence of 1 in 100.000
pregnancies. They represent approximately 1% of all GTN cases
Diagnosis of GTN
• GTN is most frequently diagnosed based on hCG values, most often without histologic
verification
• It is essential to measure hCG in any woman of childbearing age who has unexplained metastatic
disease
• A serum hCG determination and exclusion of normal pregnancy is essential to diagnose GTN in
these circumstances, which can spare the patient an unnecessary surgery to establish the diagnosis
• When a GTN diagnosis is made or suspected, immediate evaluation for metastases is needed
• A gynaecological examination should be done to exclude vaginal or pelvic metastases
• Biopsy of metastatic lesions is highly risky due to abundant vascularisation and is not essential
before starting chemotherapy
• If complete excision is possible, histologic confirmation of the diagnosis is also valuable
• Chest X-ray to diagnose lung metastases and can be used for counting the number of lung
metastases to evaluate the risk score
• Liver metastases may be diagnosed by US or CT, Brain metastases by MRI or CT
Clinical signs and symptoms
• GTN has a varying presentation depending on the antecedent pregnancy event, disease type and extent
• Post molar GTN can be associated with irregular bleeding after initial treatment for molar pregnancy, an
enlarged and irregular uterus, and bilateral ovarian enlargement.
• However, these signs may be absent.
• Patients often present with symptoms of metastatic disease
• The most common metastatic sites are the lungs, but can also be found in vagina, liver, brain, spleen, kidneys,
and bowel
• Characteristically, gestational choriocarcinoma forms a rapidly growing tumor with the ability to metastasize
to virtually every body site and present with widespread dissemination.
• Metastatic lesions often produce abnormal bleeding because trophoblastic tumors have fragile vessels
• Embolization of trophoblastic tissue is also possible, and it can cause dyspnoea, coughing, chest pain,
tachypnoea, and haemoptysis
• Vaginal metastases can present with bleeding, which cannot be distinguished from the uterine blood loss.
Post-molar GTN
• Most GTN will arise after the evacuation of a HM
• GTN following a HM is referred to as post-molar GTN
• Post-molar GTN includes invasive mole and choriocarcinoma.
• In contrast, PSTT and ETT can develop after any type of antecedent pregnancy, including normal
pregnancy, non-molar abortion, or ectopic pregnancy
• In most patients, HMs regress spontaneously after evacuation of the molar tissue, but in
approximately 15% - 20% of CHMs and 0.5% - 1% PHMs, trophoblastic tissue remains active.
• Consequently, hCG levels have a sustained rise or plateau, which indicates the need for evaluation
and treatment
Treatment of low-risk GTN
• Low-risk GTN (FIGO/WHO score <7) is primarily treated with one of two single-agent drugs
MTX or Act-D
• A variety of doses and infusion schedules for these drugs have been utilized
• There is not a clearly superior regimen between these two drugs
• Treatment therefore is often determined by institutional preference
• Chemotherapy response is monitored by hCG measurements at least every 1 or 2 weeks
• Chemotherapy resistance is indicated by plateau in hCG over 3 consecutive cycles or a rise in hCG
over 2 consecutive cycles
• Once hCG has normalized, treatment is continued for a minimum of four weeks, which represents
at least two consolidation cycles
Treatment of high-risk GTN
• High-risk GTN (FIGO/WHO score > 6) is treated with multi-agent chemotherapy, with or without
adjuvant surgery or radiotherapy
• The most used chemotherapy protocol is EMA-CO
Invasive mole
• Invasive mole arises from invasion of CHM or PHM into the myometrium and/or uterine blood
vessels
• The tendency of invasive mole to invade myometrium can result in uterine perforation and
extension to adjacent organs
• However, some degree of myometrial invasion of the trophoblast is probably present in most
moles
• The diagnosis of invasive mole can only be histologically confirmed after hysterectomy
• As hysterectomy is nowadays rarely performed, chemotherapy is usually started without histologic
confirmation of the diagnosis.
• Chemotherapy is essential to prevent further complications, although invasive moles rarely
metastasize and are usually self-limited
Choriocarcinoma
• Choriocarcinoma is the most common malignant GTN
• It is characterised by abnormal trophoblastic hyperplasia and anaplasia, absence of
chorionic villi with varying degrees of haemorrhage and necrosis.
• The tumor is mainly uterine but extrauterine sites such as fallopian tubes and
ovaries can also be involved
• Patients with gestational choriocarcinomas tend to develop early systemic
metastasis.
• Metastases have been reported in the lung, liver, spleen, kidney, bowel, or brain
• In contrast to ectopic tubal or ovarian choriocarcinoma, primary choriocarcinoma
in other organs is likely to represent non-gestational carcinoma with trophoblastic
differentiation
Placental-Site Trophoblastic Tumor (PSTT)
and Epithelioid Trophoblastic Tumor (ETT)
• PSTT and ETT are the rarest subtypes of GTN
• PSTT originates from the intermediate trophoblast on the maternal side of the placental bed with
half of the cases invading deep into the myometrium. Chorionic villi are absent
• In contrast to choriocarcinoma, PSTT forms uterine lesions with less haemorrhage. Tumor
necrosis is often extensive
• ETT is even rarer, and it develops from the chorionic type of intermediate trophoblast
• Nearly half arise in the cervix or lower segment of the uterus and some in the fundus or broad
ligament. The characteristic nodular and expansive growth mimics cervical carcinoma
• PSTT and ETT share several overlapping features. They are both slow growing tumors and can
occur months to years after any type of antecedent pregnancy
• They both produce less hCG and metastasize in later stages and have limited chemosensitivity
Treatment of PSTT and ETT
• Treatment of PSTT and ETT is determined by two independent poor prognostic factors: an interval
of ≥48 months from the causative pregnancy and stage IV disease
• Stage I tumors (confined to the uterus) arising <48 months since the antecedent pregnancy are
treated with a total abdominal hysterectomy including removal of any suspicious pelvic and
retroperitoneal lymph nodes. Adjuvant systemic therapy is not required
• In contrast, if the PSTT/ETT originated from a pregnancy > 48 months previously, then such stage
I patients and stage II–IV patients should be offered aggressive platinum-based chemotherapy
including the option for experimental treatments such as high dose chemotherapy or
immunotherapy
• Residual masses after treatment should be excised wherever possible to confirm no active cancer
remains
UNDANG-UNDANG REPUBLIK INDONESIA NOMOR 29
TAHUN 2004 TENTANG PRAKTIK KEDOKTERAN
• Pasal 51: Dokter atau dokter gigi dalam melaksanakan praktik kedokteran mempunyai kewajiban :
• a. memberikan pelayanan medis sesuai dengan standar profesi dan standar prosedur operasional
serta kebutuhan medis pasien
• b. merujuk pasien ke dokter atau dokter gigi lain yang mempunyai keahlian atau kemampuan yang
lebih baik, apabila tidak mampu melakukan suatu pemeriksaan atau pengobatan
• c. merahasiakan segala sesuatu yang diketahuinya tentang pasien, bahkan juga setelah pasien itu
meninggal dunia
• d. melakukan pertolongan darurat atas dasar perikemanusiaan, kecuali bila ia yakin ada orang lain
yang bertugas dan mampu melakukannya
• e. menambah ilmu pengetahuan dan mengikuti perkembangan ilmu kedokteran atau kedokteran
gigi.
PERATURAN KONSIL KEDOKTERAN INDONESIA NOMOR 86
TAHUN 2O2O TENTANG STANDAR PENDIDIKAN PROFESI
DOKTER SPESIALIS OBSTETRI DAN GINEKOLOGI
• Tingkat Kemampuan 4: mendiagnosis, melakukan penatalaksanaan secara
mandiri dan tuntas. Lulusan dokter mampu membuat diagnosis klinik dan
melakukan penatalaksanaan masalah tersebut secara mandiri dan tuntas.
• 4A: Kompetensi yang dicapai pada saat menyelesaikan modul
• 4B: Profisiensi (kemahiran) yang dicapai setelah menyelesaikan pendidikan
• Daftar masalah:
• 5. Molahidatidosa: 4
• 128. Penyakit trofoblas maligna low risk: 4
• 129. Penyakit trofoblas maligna high risk: 3
TERIMA KASIH