A Multicenter Retrospective Study of Epithelioid Trophoblastic Tumors to Identify the Outcomes, Prognostic Factors, and Therapeutic Strategies

Abstract

BackgroundThere is no consensus for the management of epithelioid trophoblastic tumor (ETT) up to date.ObjectiveETT is the rarest form of gestational trophoblastic neplasia (GTN). Our goal was to assess the outcomes and explore the prognostic factors of patients with ETT through this multicenter retrospective analysis and to devise a risk-adapted approach to clinical management.MethodsA total of 31 patients were validated as ETT pathologically between January 2004 and June 2021 from three tertiary hospitals. We retrospectively analyzed the characteristics, treatments, outcomes, and prognostic factors.ResultsEight patients experienced a recurrence, and 6 patients died of ETT, resulting in a mortality rate of 19.4%. Five patients with stage I disease had a fertility-preserving treatment. Among them, one patient had a full-term delivery, whereas a 23-year-old patient who declined a hysterectomy died of a recurrent disease. Eight patients of extrauterine ETT with isolated pulmonary lesion were at a young age at diagnosis (median: 30.5 vs. 41, p = 0.003) and had a smaller tumor size (median: 2.4 vs. 4.8 cm, p = 0.003) compared with other patients who had a metastatic disease, and none of them died. The multivariate analyses showed that the number of metastases ≥3 [hazard ratio (HR), 28.16, p = 0.003] was the only significant predictor associated with adverse overall survival, while the number of metastases ≥3 (HR 9.59, p = 0.005) and chemotherapy alone (HR 16.42, p = 0.001) were associated with adverse recurrence-free survival. Patients in stage I or with number of metastases <3 had a favorable prognosis, whereas the prognosis of patients whose number of metastases ≥3 remains poor.ConclusionsChemotherapy alone is insufficient for patients with ETT. Surgical procedures are the mainstay of management for ETT patients. Combined surgery and multi-agent chemotherapy are recommended for patients with metastatic disease and localized disease with persistently positive human chorionic gonadotrophin levels after surgery. The number of metastases at ≥3 is the most critical risk factor for ETT.

The fertility-sparing treatment and outcome of epithelioid trophoblastic tumor isolated to lung: a case report and review literature

“…Lung metastasis comes to stage III where hysterectomy with salpingectomy and excision of metastatic disease are recommended if feasible ( 12 ). However, the favorable outcome of ETT patients with isolated pulmonary lesions resembles that of patients in stage I ( 8 ). There were no reported fatalities in 28 cases of isolated pulmonary ETT ( Table 1 ).…”

“…Due to the low incidence of ETT, there are yet no consensus on poor prognostic factors. Some researchers included the interval of over 4 years ( 1 ) [or over 2 years ( 7 )] from the preceding pregnancy as a risk factor for ETT prognosis besides patient age (≥ 40 years) ( 11 ), a high mitotic count (>5–10 MFs/10 HPFs) ( 11 ), and the number of metastatic lesions (≥3) ( 8 ). Lung metastasis comes to stage III where hysterectomy with salpingectomy and excision of metastatic disease are recommended if feasible ( 12 ).…”

“…In the previously reported 28 cases of isolated pulmonary ETT, operations were performed ( 2 , 8 , 12 – 22 ) ( Table 1 ). Among these cases, 21 cases underwent thoracic surgery without hysterectomy (T-H), while seven cases had the isolated lung lesions removed along with total uterine (T+H) where postoperative pathology revealed a benign disease in uterine.…”

Extrauterine epithelioid trophoblastic tumour and its somatic carcinoma mimics: short tandem repeat genotyping meets the diagnostic challenges

“…A monomorphic choriocarcinoma or mixed trophoblastic tumour was a possibility, given its diffuse hCG immunohistochemistry staining pattern and high Ki67 index (60%). Multiple reported cases of treated gestational choriocarcinoma developed recurrent or metastatic tumours with histological features overlapping with ETT 43–45 . One scenario argues for the existence of mixed trophoblastic tumours with a predominantly choriocarcinoma component and a minor and inconspicuous ETT component that is generally resistant to chemotherapy.…”

“…Multiple reported cases of treated gestational choriocarcinoma developed recurrent or metastatic tumours with histological features overlapping with ETT. [43][44][45] One scenario argues for the existence of mixed trophoblastic tumours with a predominantly choriocarcinoma component and a minor and inconspicuous ETT component that is generally resistant to chemotherapy. The latter ETT component may become a post-chemotherapy-dominant tumour type upon elimination of the chemo-sensitive choriocarcinoma element.…”