Clinical characteristics and prognosis of ultra high-risk gestational trophoblastic neoplasia patients: A retrospective cohort study

https://doi.org/10.1016/j.ygyno.2017.04.010Get rights and content

Highlights

  • Ultra high-risk gestational trophoblastic neoplasia patients have a poor prognosis.

  • The FAEV regimen is effective chemotherapy with manageable toxicity for GTN.

  • Prognosis-related risk factors for ultra high-risk GTN patients are revealed.

Abstract

Objective

The gestational trophoblastic neoplasia (GTN) patients with the International Federation of Gynecology and Obstetrics (FIGO) score  12 are defined as ultra high-risk GTN. This study aims to investigate the clinical characteristics, the treatment efficiency, and the prognosis of ultra high-risk GTN patients.

Methods

Between January 2002 and December 2015, medical record data of 143 GTN patients with FIGO score  12 at Peking Union Medical College Hospital (PUMCH) were reviewed. Ratios were compared using chi-square test, and prognostic risk factors were analyzed by univariate analysis and multivariate analysis.

Results

Among the 143 ultra high-risk GTN patients, 94 (65.7%) patients had achieved complete remission and 15.9% (15/94) patients relapsed after complete remission. The 5-year overall survival (OS) rate of the entire cohort approached 67.9%. The results of the multivariate analysis revealed that non-molar antecedent pregnancy [Relative risk (RR) 4.689, 95% CI 1.448–15.189, P = 0.010], brain metastases (RR 2.280, 95% CI 1.248–4.163, P = 0.007), previous failed multiagent chemotherapy (RR 5.345, 95% CI 2.222–12.857, P = 0.000) and surgery (RR 0.336, 95% CI 0.177–0.641, P = 0.001) all had influence on the prognosis of ultra high-risk GTN patients.

Conclusions

GTN patients with FIGO score  12 have a poor prognosis. More emphasis should be placed on non-molar antecedent pregnancy, brain metastases, and previous multiagent chemotherapy failure. Moreover, salvage surgery may improve the prognosis. Floxuridine-based multiagent chemotherapy is effective with manageable toxicity for ultra high-risk GTN patients.

Introduction

Gestational trophoblastic neoplasia (GTN) refers to a group of uncommon malignant gynecological tumors caused by abnormal proliferation of trophoblastic tissues. GTN consists of invasive mole, choriocarcinoma, placental site trophoblastic tumor (PSTT) and epitheliloid trophoblastic tumor (ETT). The International Federation of Gynecology and Obstetrics (FIGO) scoring system is used to predict prognosis of GTN patients. Low-risk GTN patients (FIGO score < 7) should be treated with single-agent. High-risk GTN patients (FIGO score  7) require multiagent chemotherapy [1]. The EMA/CO regimen (etoposide, methotrexate, actinomycin-D, cyclophosphamide, vincristine) is commonly used worldwide [2]. The overall survival (OS) rate almost approaches 100% in low-risk patients (FIGO score < 7), whereas high-risk patients (FIGO score  7) can achieve a survival rate of 80–90% [3]. However, the survival rate of high-risk patients is misleading because the prognosis of these patients is definitely different. Bolze showed that the patients with FIGO score  13 had an obviously higher 5-year death rate than the patients with FIGO score < 13 (38.4% and 4.9%, P < 0.001) [4]. Other literatures also suggested that FIGO score  12 is an independent risk factor for poor prognosis [5], [6], [7], [8]. Therefore, FIGO Cancer Report 2015 divided the GTN patients with FIGO score  7 into high-risk subgroup (7  FIGO score < 12) and ultra high-risk subgroup (FIGO score  12) [9]. However, limited information is available about ultra high-risk subgroup so far because of its rarity [10], [11].

Herein we conducted the retrospective study to analyze the clinical characteristics, the treatment efficiency and the prognosis of the ultra high-risk GTN patients treated at Peking Union Medical College Hospital (PUMCH). To the best of our knowledge, this study contained the largest sample size to date, and we revealed the prognostic risk factors of ultra high-risk GTN patients for the first time.

Section snippets

Patients

Between January 2002 and December 2015, a total of 1776 patients were diagnosed with GTN at Peking Union Medical College Hospital (PUMCH). Among these patients, 143 (8.1%) patients were defined as ultra high-risk patients with FIGO score  12, of whom 41 patients received initial chemotherapy in our hospital while the other 102 patients were transferred from other hospitals with a history of failed chemotherapy. The database and medical records were reviewed to extract the basic information,

Clinical characteristics

All of the 143 ultra high-risk GTN patients in this study were diagnosed with choriocarcinoma. The majority of the patients were diagnosed with choriocarcinoma based on clinical findings, including detailed medical history, physical examination, serum β-hCG levels, transvaginal or transabdominal sonography, chest X-ray or computed tomography (CT). Pathological evidence was not necessary for the diagnosis of choriocarcinoma. Only a minority of these patients had pathological evidences before the

Discussion

In our study, the ultra high-risk GTN accounted for 8.1% of the entire GTN cohort. Of the 143 ultra high-risk GTN patients, only 4 (2.8%) patients were at stage I, 3 (2.1%) patients were at stage II, and the other 136 (95.1%) patients were all at stage III or IV. Although the 7 cases were just at Stage I or II, six patients of them had previous chemotherapy failures and all of them had uterine lesions. Therefore, FAEV chemotherapy was given to them and six of them underwent hysterectomy or

Conflict of interest statement

We declare that we have no financial interest, commercial interest and/or other relationships with other people or organizations that can inappropriately influence our work.

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      Low-risk patients are treated with single-agent chemotherapy, whereas high-risk patients receive multi-agent chemotherapy to prevent resistance. With the development of effective chemotherapy regimens, GTN has become highly curable, with remission rates of up to 100% for low-risk GTNs [4], 94–95% for high-risk GTNs including ultra-high-risk cases, and 65% for ultra-high-risk GTNs [5,6]. In the current FIGO 2000 prognostic scoring system, prognostic factors of GTN include antecedent pregnancy, pre-treatment β-human chorionic gonadotropin (β-hCG), the interval from the index pregnancy, tumour size, site of metastases, number of metastases identified, and history of chemotherapy failure [2,7].

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      Patients with low-risk gestational trophoblastic neoplasia are usually treated with a single-drug chemotherapy regimen; multidrug chemotherapy regimens are used for high-risk gestational trophoblastic neoplasia.1,3 Although complete response is reported in more than 90% of patients with high-risk disease after primary chemotherapy (eg, etoposide, methotrexate, and dactinomycin [EMA] plus cyclophosphamide and vincristine [CO], EMA plus etoposide and cisplatin [EP], and floxuridine, dactinomycin, etoposide, and vincristine [FAEV] regimens),1,3,4 about 5% of patients with high-risk disease patients develop chemorefractory disease, or have multiple relapses and die of disease progression.4–6 Brain and liver metastases,7,8 multidrug chemotherapy-resistant tumours,9 and infrequent pathological types (placental site trophoblastic tumour and epithelioid trophoblastic tumour)10 are adverse features that predict poorer outcomes.

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      The score is associated with the risk of developing chemoresistance to single-agent chemotherapy, and thus guides the choice of first-line chemotherapy [9,10]. Although patients with high-risk GTN can achieve a survival rate of 80–90%, it is observed that patients with a FIGO score ≥12 have a higher 5-year death rate, being an independent risk factor for poor prognosis and therefore classified as “ultra” high-risk GTN [16–18]. Of note, the WHO Prognostic Scoring System is not applicable to patients with PSTT or ETT [9,10].

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