Abstract Placental site trophoblastic tumour (PSTT) is a very rare and unique form of gestational trophoblastic disease (GTD). This tumour represents a neoplastic transformation of intermediate trophoblastic cells that normally play a critical role in implantation. PSTT can occur after a normal pregnancy, abortion, term delivery, ectopic pregnancy or molar pregnancy. It displays a wide clinical spectrum, and when metastatic, can be difficult to control even with surgery and chemotherapy. Unlike other forms of GTD, PSTT is characterized by low beta-hCG levels because it is a neoplastic proliferation of intermediate trophoblastic cells. Expression, however, of human placental lactogen (hPL) is increased on histologic section as well as in the serum. The most common presenting symptoms of PSTT are vaginal bleeding and amenorrhoea. Diagnosis is confirmed by dilatation and curettage (D and E) and hysterectomy but meticulous evaluation of metastasis is mandatory. Most cases are confined to the uterus but pelvic involvement, lung and other organ metastasis has been reported. Unlike other forms of GTD, the WHO prognostic score is of little help. For the PSTT patient, surgery is the primary treatment of choice. For patients desiring future childbearing, D and C and adjuvant chemotherapy is an option. Because these tumours tend to be less sensitive than other types of GTD to chemotherapy, the most successful regimen to date has been with EMA/CO or EMA/EP. Treatment Protocols Most women with gestational trophoblastic neoplasia (GTN) receive their diagnosis during their reproductive years. An important aspect of treatment is curing GTN while attempting to preserve future fertility. Fortunately, GTN is very sensitive to chemotherapy. Chemotherapeutic treatment recommendations are based on stage, World Health Organization (WHO) prognostic score, and histology. Treatment recommendations for low-risk GTN (prognostic score, 0-6) Consider the following: Methotrexate (MTX) and dactinomycin (Act-D) are the two single agents used to treat GTN; there is no standard regimen. Many practitioners use a 5-day MTX regimen or an alternating 8-day MTX regimen because of high response rates. Ease of administration and cost favor regimens such as weekly MTX or biweekly (pulsed) Act-D; however, risks associated with extravasation of Act-D and adverse effects such as alopecia and neutropenia make MTX regimens more commonly used as front-line therapy Four randomized, controlled trials have demonstrated a superiority of pulsed Act-D over weekly MTX, and in 2011, the Gynecologic Oncology Group (GOG) reported on the superiority of pulsed Act-D over weekly MTX; however, the clinical relevance of these results has been questioned because many practitioners use a 5-day MTX regimen or an alternating 8-day MTX regimen, with response to these treatments being superior to those for weekly MTX regimens. If a single-agent drug regimen fails in low-risk patients, they may continue to be eligible for an alternative single-agent regimen. Charing Cross Hospital has proposed that in patients with MTX resistance but with continued low-risk International Federation of Gynecology and Obstetrics (FIGO) scores, as well as a beta-human chorionic gonadotropin (beta-hCG) level of less than 100 IU/L, a 5-day Act-D regimen may be appropriate; however, if the beta-hCG level is greater than 100 IU/L, a multidrug regimen may be more appropriate. Treatment recommendations for high-risk GTN (prognostic score, ≥7) and FIGO stage IV A multidrug regimen is the initial therapy in patients with high-risk GTN; while no randomized trials have compared regimens, the multidrug regimen of etoposide, MTX, Act-D, cyclophosphamide, and vincristine (EMA-CO) is the one most commonly used and is considered to be the standard of care. Bower et al reported on a series using EMA-CO; the 5-year survival rate was 86.2%; in this series, patients with brain metastases received an increased dose of MTX to 1 g/m2 IV infused over 24 hours, followed by folinic acid. In patients in whom hCG levels plateau or increase during or after EMA-CO, a drug regimen of etoposide, MTX, folinic acid, and cisplatin (EMA-EP) is used. Good prognosis is anticipated in cases localized to the uterus, and when the interval between antecedent pregnancy and treatment is less than 2 years. In cases with distant metastasis or delayed treatment, the outcome is dismal. Advances in chemotherapeutic regimens have improved clinical reponse in metastatic disease. Source 1 Source 2
