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Guideline No. 408: Management of Gestational Trophoblastic Diseases

      Abstract

      Objective

      This guideline reviews the clinical evaluation and management of gestational trophoblastic diseases, including surgical and medical management of benign, premalignant, and malignant entities. The objective of this guideline is to assist health care providers in promptly diagnosing gestational trophoblastic diseases, to standardize treatment and follow-up, and to ensure early specialized care of patients with malignant or metastatic disease.

      Intended Users

      General gynaecologists, obstetricians, family physicians, midwives, emergency department physicians, anaesthesiologists, radiologists, pathologists, registered nurses, nurse practitioners, residents, gynaecologic oncologists, medical oncologists, radiation oncologists, surgeons, general practitioners in oncology, oncology nurses, pharmacists, physician assistants, and other health care providers who treat patients with gestational trophoblastic diseases. This guideline is also intended to provide information for interested parties who provide follow-up care for these patients following treatment.

      Target Population

      Women of reproductive age with gestational trophoblastic diseases.

      Options

      Women diagnosed with a gestational trophoblastic disease should be referred to a gynaecologist for initial evaluation and consideration for primary surgery (uterine evacuation or hysterectomy) and follow-up. Women diagnosed with gestational trophoblastic neoplasia should be referred to a gynaecologic oncologist for staging, risk scoring, and consideration for primary surgery or systemic therapy (single- or multi-agent chemotherapy) with the potential need for additional therapies. All cases of gestational trophoblastic neoplasia should be discussed at a multidisciplinary cancer case conference and registered in a centralized (regional and/or national) database.

      Evidence

      Relevant studies from 2002 onwards were searched in Embase, MEDLINE, the Cochrane Central Register of Controlled Trials, and Cochrane Systematic Reviews using the following terms, either alone or in combination: trophoblastic neoplasms, choriocarcinoma, trophoblastic tumor, placental site, gestational trophoblastic disease, hydatidiform mole, drug therapy, surgical therapy, radiotherapy, cure, complications, recurrence, survival, prognosis, pregnancy outcome, disease outcome, treatment outcome, and remission. The initial search was performed in April 2017 and updated in May 2019. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional significant articles were identified through cross-referencing the identified reviews. The total number of studies identified was 673, with 79 studies cited in this review.

      Validation Methods

      The content and recommendations were drafted and agreed upon by the authors. The Executive and Board of Directors of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of Directors for the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework. See the online appendix tables for key to grading and interpretation of recommendations.

      Benefits

      These guidelines will assist physicians in promptly diagnosing gestational trophoblastic diseases and urgently referring patients diagnosed with gestational trophoblastic neoplasia to gynaecologic oncology for specialized management. Treating gestational trophoblastic neoplasia in specialized centres with the use of centralized databases allows for capturing and comparing data on treatment outcomes of patients with these rare tumours and for optimizing patient care.

      SUMMARY STATEMENTS (GRADE ratings in parentheses)

      • 1
        If symptoms of pregnancy persist 4 to 6 weeks after termination of pregnancy, evacuation of a nonviable pregnancy, or spontaneous abortion, measurement of serum or urine human chorionic gonadotropin may allow for earlier diagnosis of gestational trophoblastic disease if products of conception are not sent routinely for pathology (moderate).
      • 2
        The differentiation of complete hydatidiform mole, partial hydatidiform mole, and malignant trophoblastic disease by a gynaecologic pathologist allows for tailored follow-up and management of gestational trophoblastic neoplasia (low).
      • 3
        The treatment of hydatidiform mole consists of surgical evacuation by suction dilatation and curettage or hysterectomy followed by human chorionic gonadotropin surveillance (moderate).
      • 4
        Prophylactic chemotherapy is considered only for high-risk patients who are unlikely to return for regular follow-up (very low).
      • 5
        Post-molar follow-up consists primarily of serial human chorionic gonadotropin monitoring (high).
      • 6
        Hormonal contraception can be safely prescribed and intrauterine contraceptive devices can be inserted after normalization of human chorionic gonadotropin levels (low).
      • 7
        Referral for genetic counseling and testing should be arranged for women with recurrent gestational trophoblastic disease as this is a rare scenario that may be associated with a familial gene mutation (moderate).
      • 8
        The finding of a persistent low-level human chorionic gonadotropin may be benign (e.g., false-positive human chorionic gonadotropin or pituitary production of human chorionic gonadotropin), premalignant (e.g., quiescent gestational trophoblastic disease), or malignant (e.g., placental site trophoblastic tumour or epithelioid trophoblastic tumour) (moderate).
      • 9
        Long-term follow-up may eventually reveal a diagnosis of gestational trophoblastic neoplasia for patients with a true positive human chorionic gonadotropin result but no immediate evidence of disease at the time of testing (low).

      RECOMMENDATIONS (GRADE ratings in parentheses)

      • 1
        Women of reproductive age presenting with abnormal uterine bleeding, bleeding >6 weeks following pregnancy, or evidence of metastatic disease should have serum human chorionic gonadotropin levels tested in order to promptly diagnose and manage gestational trophoblastic disease (strong, low).
      • 2
        Any products of conception that appear abnormal at the time of dilatation and curettage should undergo histologic examination to rule out gestational trophoblastic disease (strong, very low).
      • 3
        Initial workup for post-molar gestational trophoblastic neoplasia requires a chest X-ray to look for lung metastases and a pelvic ultrasound scan to assess extent of disease in the pelvis (strong, moderate).
      • 4
        Initial workup for suspected choriocarcinoma, gestational trophoblastic neoplasia after a non-molar pregnancy, and/or post-molar gestational trophoblastic neoplasia with lung metastases on chest X-ray requires pelvic ultrasound scan, computed tomography scan of the chest and abdomen (with arterial phase through the liver), and magnetic resonance imaging of the brain (strong, moderate).
      • 5
        Women with suspected hydatidiform mole should be offered either suction evacuation of the uterus or hysterectomy for initial management (strong, moderate).
      • 6
        All Rh-negative women should be offered anti-D immune globulin after uterine evacuation to prevent alloimmunization (strong, high).
      • 7
        For all patients after evacuation of a molar pregnancy, weekly monitoring of serum quantitative human chorionic gonadotropin should begin 2 weeks post-procedure and continue until levels remain undetectable for 3 consecutive weeks. For complete hydatidiform mole, human chorionic gonadotropin should continue to be monitored monthly for 6 months. For partial hydatidiform mole, human chorionic gonadotropin should be measured 1 month after the first undetectable result to confirm resolution (strong, high).
      • 8
        Women undergoing follow-up after molar pregnancy should receive reliable contraception throughout the entire duration of follow-up (strong, moderate).
      • 9
        For women with previous gestational trophoblastic neoplasia or recurrent molar pregnancy, follow-up in a subsequent pregnancy should include early ultrasound scan, close examination of the placenta, and histologic examination of any nonviable pregnancy (strong, high).
      • 10
        Women diagnosed with gestational trophoblastic neoplasia should be promptly referred to a specialist in gynaecologic oncology for staging, risk scoring, and treatment (strong, high).
      • 11
        Women with low-risk gestational trophoblastic neoplasia should undergo treatment with single-agent chemotherapy, although hysterectomy is an option for select patients (strong, high).
      • 12
        Women with high-risk gestational trophoblastic neoplasia should undergo treatment with multi-agent chemotherapy at a centre with expertise in managing this disease (strong, high).
      • 13
        Ultrahigh-risk gestational trophoblastic neoplasia with liver or brain metastasis or a modified World Health Organization score as adapted by the International Federation of Gynecology and Obstetrics (FIGO),

        FIGO Committee on Gynecologic Oncology. Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia. Int J Gynaecol Obstet. 2009;105:3–4.

        of ≥13 should undergo low-dose induction chemotherapy with etoposide and cisplatin weekly for 1 to 3 weeks to avoid complications of uncontrolled hemorrhage followed by multi-agent chemotherapy at a centre with expertise in managing this disease, preferably at a reference centre (strong, high).
      • 14
        Women who become pregnant during follow-up for gestational trophoblastic disease or gestational trophoblastic neoplasia should be referred to gynaecologic oncology and maternal–fetal medicine for assessment and management (strong, very low).
      • 15
        The care of patients with gestational trophoblastic disease should be managed in specialized centres and their data recorded in centralized (regional and/or national) registries, where possible (strong, high).

      Keywords

      Abbreviations:

      GTD (Gestational trophoblastic disease), GTN (Gestational trophoblastic neoplasia), hCG (Human chorionic gonadotropin), hCG-H (Hyperglycosylated human chorionic gonadotropin)
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