Gestational trophoblastic neoplasia after human chorionic gonadotropin normalization in a retrospective cohort of 7761 patients in France.

BACKGROUND: The risk of malignant transformation of molar pregnancies after human chorionic gonadotropin levels return to normal is low, roughly 0.4%, but may justify an adaptation of monitoring strategies for certain patients. OBJECTIVE: This study aimed to determine the risk of gestational trophoblastic neoplasia after human chorionic gonadotropin normalization in women with molar pregnancy and identify risk factors for this type of malignant transformation to optimize follow-up protocols after human chorionic gonadotropin normalization. STUDY DESIGN: This was a retrospective observational national cohort study based at the French National Center for Trophoblastic Diseases of 7761 patients, treated between 1999 and 2020 for gestational trophoblastic disease, whose human chorionic gonadotropin levels returned spontaneously to normal. RESULTS: Among 7761 patients whose human chorionic gonadotropin levels returned to normal, 20 (0.26%) developed gestational trophoblastic neoplasia. The risk of malignant transformation varied with the type of mole, from 0% (0 of 2592 cases) for histologically proven partial mole to 0.36% for complete mole (18 of 5045) and 2.1% (2 of 95) for twin molar pregnancy. The median time to diagnosis of malignant transformation after human chorionic gonadotropin normalization was 11.4 months (range, 1-34 months). At diagnosis, 16 of 20 patients (80%) had the International Federation of Gynecology and Obstetrics stage I tumor, and 10 of 20 patients (50%) had a tumor classified as low risk in terms of the International Federation of Gynecology and Obstetrics score. In 9 of 20 patients (45%), the most common first-line treatment was combination chemotherapy. A quarter of these tumors (5 of 20) were histologically proven placental site or epithelioid trophoblastic tumors. In univariate analysis, the factors significantly associated with a higher risk of developing gestational trophoblastic neoplasia after the end of the normal human chorionic gonadotropin monitoring period were age of ≥45 years (odds ratio, 8.3; 95% confidence interval, 2.0-32.7; P=.004) and time to human chorionic gonadotropin normalization of ≥8 weeks (odds ratio, 7.7; 95% confidence interval, 1.1-335; P=.03). The risk was even higher for human chorionic gonadotropin normalization times of ≥17 weeks (odds ratio, 19.5; 95% confidence interval, 3.3-206; P<.001). CONCLUSION: In this group of patients with gestational trophoblastic disease, none of the those with pathologically verified partial mole had malignant transformation, supporting the current recommendation of stopping human chorionic gonadotropin monitoring after 3 successive negative tests. In cases of complete mole or twin molar pregnancy, we proposed to extend the monitoring period with quarterly human chorionic gonadotropin measurements for an additional 30 months in patients with the identified risk factors for late malignant transformation (age, ≥45 years; time to human chorionic gonadotropin normalization, ≥8 weeks).

The management of hydatidiform mole using prophylactic chemotherapy and hysterectomy for high-risk patients decreased the incidence of gestational trophoblastic neoplasia in Vietnam: a retrospective observational study.

The management of hydatidiform mole (HM) and the incidence of post-molar gestational trophoblastic neoplasia (GTN) in Vietnam has not been reported to date. This study aimed to study the incidence of HM and post-molar GTN and identify factors associated with post-molar GTN at a tertiary hospital in Vietnam. Five hundred and eighty-four patients who were treated for HM at Tu Du Hospital between January and December 2010 were included in this study. The mean age and gestational age at the first evacuation were 28.8 years old and 11.0 weeks, respectively. After the initial evacuation and pathological examination, 87 patients who were older than 40 or did not wish to have children underwent a hysterectomy, while the others underwent second curettage. All 472 patients who had human chorionic gonadotropin (hCG) ≥ 100,000 IU/L before treatment received one cycle of methotrexate with folinic acid as prophylactic chemotherapy. The incidence of HM was 11.1 per 1,000 deliveries; 47 patients (8.0%) developed post-molar GTN. Gestational week, hCG level at one week after the first evacuation, and pathological remnants were significantly associated with the development of post-molar GTN. The results of this study suggest that prophylactic chemotherapy and hysterectomy may be useful for high-risk HM patients to reduce post-molar GTN in settings in which the risk of post-molar GTN and loss to follow-up after HM are greater and hCG measurements and appropriate GTN treatments are unavailable. However, future studies on the long-term outcomes and side effects of prophylactic therapies on HM are required.

Historical, morphological and clinical overview of placental site trophoblastic tumors: from bench to bedside.

INTRODUCTION: Placental site trophoblastic tumor (PSTT) is a form of gestational trophoblastic disease that originates from the implantation of an intermediate trophoblast. It was described for the first time by Von F. Marchand in 1895 as belonging to chorioepithelioma sui generis, a pathological condition with many variations and a progressive degree of malignancy. METHODS: We have conducted a literature review in MEDLINE about epidemiology, etiopathogenesis and clinical features of PSTT. Moreover, a case that occurred in our institution was reported. RESULTS: Our research has highlighted that existing published data about PSTT are not uniform. The number of cases described in the literature has updated and the clinical features of selected "case series" of patients diagnosed with PSTT were showed. The etiopathogenesis was discussed. It was noted that current prognostic factors still allow important information regarding PSTT to be obtained, albeit fragmentary. CONCLUSIONS: The lack of uniformity in data collection seen so far has limited full knowledge of PSTT. For this reason, we suggest a model (PSTT model) that collects and unifies PSTT evidence as this would be useful to identify worldwide precise prognostic factors, which are still lacking. When PSTT is diagnosed, the proper procedure seems to be total hysterectomy, with sampling of pelvic lymph nodes and ovarian conservation. For advanced-stage diseases, (stage III and IV) a combination of surgery and polychemotherapy is suggested.

Long-term outcome of patients with persistent low-level elevation of human chorionic gonadotrophin.

AIM: The aim of this study was to investigate a series of patients with sustained low-level elevated human chorionic gonadotrophin (hCG) and explore the management of these patients. METHODS: A total of 47 patients with persistent low levels of hCG were selected for analysis between January 2002 and January 2014 at the Women's Hospital of Zhejiang University, Hangzhou, China. Data were retrospectively reviewed for patient characteristics, therapeutic strategies, and follow-ups. We compared the characteristics of patients who were and were not eventually considered to have malignancies. RESULTS: Among the 47 patients, 17 with persistent low-level elevated hCG and no detectable lesions were considered to have no active malignancy. Fifteen of the 17 patients had hCG levels that returned to normal range by the end of follow-up, while the remaining two did not. The other 30 patients were eventually diagnosed as having active malignancies due to detected lesions or increasing elevation of hCG. A large proportion of these patients were diagnosed with placental site trophoblastic tumor or epithelioid trophoblastic tumor. CONCLUSION: For patients with persistent low-level elevated hCG, frequent follow-up rather than any therapy is recommended. Treatment was considered effective and safe once diagnosis of active malignancy was confirmed.

Epidemiological report on the treatment of patients with gestational trophoblastic disease in 10 Brazilian referral centers: results after 12 years since International FIGO 2000 Consensus.

OBJECTIVE: To evaluate treatment of Brazilian patients with gestational trophoblastic disease (GTD). STUDY DESIGN: A retrospective cohort study with analysis of medical reports performed in 10 Brazilian referral centers from January 2000 to December 2011. RESULTS: Of 5,250 patients 3 died (0.06%) at the time of uterine evacuation. Spontaneous remission of GTD (group G1) was observed in 4,103 cases, and 1,144 (21.8%) progressed to gestational trophoblastic neoplasia (GTN) (G2). In G1 2,716 (66.2%) had complete hydatidiform mole (HM) and 1,210, partial HM (29.5%); 3,772 patients (92.7%) recovered as noted in December 2012. In G2, of 1,118 patients treated, initial histopathological results of previous gestation were complete HM (77.5% [n = 886]), partial HM (8.8% [n = 100]), and choriocarcinoma (8.0% [n = 92]); 930 (81.3%) were low-risk, 200 (17.5%) were high-risk GTN, and 14 had placental site trophoblastic tumor (PSTT) (1.2%); cure was achieved in 1,078 cases (96.4%), but 26 patients (2.3%) died (4 low-risk [0.4%], 19 high-risk [9.5%], and 3 PSTT [21.4%]). CONCLUSION: The highest death rates were due to high-risk GTN and PSTT. Patients with molar pregnancy should be referred to a referral center for an early diagnosis and prompt treatment of GTN in order to reduce the morbidity and mortality found in advanced stages.

Multicenter analysis of gestational trophoblastic neoplasia in Turkey.

BACKGROUND: To evaluate the incidence, diagnosis and management of GTN among 28 centers in Turkey. MATERIALS AND METHODS: A retrospective study was designed to include GTN patients attending 28 centers in the 10-year period between January 2003 and May 2013. Demographical characteristics of the patients, histopathological diagnosis, the International Federation of Gynecology and Obstetrics (FIGO) anatomical and prognostic scores, use of single-agent and multi-agent chemotherapy, surgical interventions and prognosis were evaluated. RESULTS: From 2003-2013, there were 1,173,235 deliveries and 456 GTN cases at the 28 centers. The incidence was calculated to be 0.38 per 1,000 deliveries. According to the evaluated data of 364 patients, the median age at diagnosis was 31 years (range, 15-59 years). A histopathological diagnosis was present for 45.1% of the patients, and invasive mole, choriocarcinoma and PSTTs were diagnosed in 22.3% (n=81), 18.1% (n=66) and 4.7% (n=17) of the patients, respectively. Regarding final prognosis, 352 (96.7%) of the patients had remission, and 7 (1.9%) had persistence, whereas the disease was mortal for 5 (1.4%) of the patients. CONCLUSIONS: Because of the differences between countries, it is important to provide national registration systems and special clinics for the accurate diagnosis and treatment of GTN.

[Management of gestational trophoblastic disease]. / Prise en charge d'une tumeur trophoblastique gestationnelle.

Gestational trophoblastic diseases comprise of hydatiform mole, invasive mole, choriocarcinoma and placental site trophoblastic tumor. Most of those pathologies are chemosensitive and have excellent prognosis, allowing preserving women's fertility because of the low relapse rate during further pregnancies. Physiopathological mechanisms and risk factors are now better understood. Hydatiform moles have to be treated by suction rather than curettage. Placental site trophoblastic tumors are particular chemoresistant pathologies, not secreting hCG which needs specific management. Trophoblastic tumors can be divided into two groups: a low risk group treated by monotherapy, most often by Methotrexate or actinomycine D, with survey about 100% and a high risk group treated by polychemotherapy (Etoposide, Methotrexate, actinomycine D, cyclophosphamide, Vincristine with survey of 86%. Chemorefractarory patients keep deep prognosis with 5 years survival rate of 43%, which allow development of new therapy in this indication. Measurement of hCG remains today central for supervision. A specialised management by an experimented team is essential to give patients better chance of recovery.

Gestational trophoblastic disease: experience at Nawabshah Hospital.

BACKGROUND: Gestational Trophoblastic Disease (GTD) is a heterogeneous group of diseases that includes partial and complete hydatidiform mole, invasive mole, choriocarcinoma and placental site trophoblastic tumour. The incidence of GTD varies in different parts of the world. The malignant potential of this disease is higher in South East Asia in comparison to western countries. Objectives of study were to determine the frequency, clinical presentation and management outcomes of GTD. This retrospective, descriptive case series was conducted in the Department of Obstetric and Gynaecology Nawabshah Medical College Hospital, from 1st Jan 2007 to 30th Dec 2007. METHODS: The case records of all the gestational trophoblastic cases during study period were analysed regarding their history, clinical examination, investigations, treatment and follow-up. The main outcomes were measured in terms of duration, antecedent pregnancy, investigations, treatment and the follow-up. RESULTS: There were a total of 1056 Obstetric admissions during the study period, which included 30 cases of trophoblastic disease with a frequency of GTD was 28 per 1000 live births. Of these 30 cases, 21 (70%) patients had hydatidiform mole, 7 (23.3%) patients had invasive disease and 2 (6.6%) patients had choriocarcinoma. Twenty three patients (76.6%) received chemotherapy while 25 (83.3%) patients had suction evacuation and 4 (13.3%) patients underwent hysterectomy. Among all patients, 29 (96.7%) fully recovered and 1 (3.3%) died because of extensive disease; metastasis extending up to brain. CONCLUSION: Frequency of GTD was higher compared to national and international studies. The disease was common in extremes of ages, low para and grand multiparous women. Hydatidiform mole was the commonest type of trophoblastic disease in these patients. Most common presenting complaint was bleeding per vagina followed by pain in lower abdomen.

Decreased breast cancer rates among women with choriocarcinoma.

OBJECTIVE: We hypothesized that exposure to high levels of hCG in women diagnosed with choriocarcinoma would decrease future breast cancer risk. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) registry limited-use database (1973-2004) to search for placenta tumors (ICD-10 C58), i.e. choriocarcinoma (CC). Demographics were obtained including patient ID, primary site, year of diagnosis, sex, race, DOB, age group and survival months. Patients with initial choriocarcinoma were searched for subsequent breast cancers. The cohort diagnosis with CC and subsequent breast cancers were compared to general population-based rates of breast cancer. RESULTS: A query for CC yielded 646 women between the ages 15 and 54 years. Of the 646 women, 422 were white, 129 African-American, and 95 "other". Total women-years of observation were 7165.3 with two CC patients developing breast cancer yielding a breast cancer incidence rate of 27.9/100,000 women-years. The incidence rate ratio(IRR) of the CC cohort to the general population was 0.21 (95% CI(0.145-0.327); P<0.01). In women with CC under the age of 35 years the breast cancer rate was 34.1/100,000, IRR 0.27 (95% CI(0.182-0.386); P<0.01). Controlling for race, breast cancer rates in whites were 49.3/100,000 (IRR 0.37, P<0.01); in African-American 1.3/100,000 (IRR 0.01, P<0.001); and 2.6/100,000 (IRR 0.03, P<0.001) in "others" compared to the general population. CONCLUSION: Women with prior CC had a 79% reduction in breast cancer risk compared to the general population regardless of age and race. Given the high level of hCG and decreased rate of breast cancer among women with CC, the hypothesis that hCG is protective against breast cancer seems plausible.

[Survey of gestational trophoblastic disease incidence among 3.6 million pregnancies in China].

OBJECTIVE: To survey incidence of gestational trophoblastic disease (GTD) in China and to provide useful information for prevention and better treatment of the disease. METHODS: The survey was retrospectively carried out from 1991 to 2000 and included 143 hospitals in the following seven Chinese provinces: Zhejiang, Jiangsu, Fujian, Anhui, Jiangxi, Shanxi and Henan. RESULTS: Excluding incomplete data, data from 118 hospitals from seven provinces were finally analyzed. The total numbers of pregnancy and GTD were 3,674, 654 and 14,222, respectively. The GTD cases occurred mainly among 20 - 34 year old women, which accounted for 85.5% of total GTD. The incidence of GTD was 3.87 per thousand. There were 9,194 cases (64.6%) of hydatidiform, 3,452 cases (24.3%) of invasive mole, 1521 cases (10.7%) of choriocarcinoma, 55 cases (0.4%) of placenta-site trophoblastic tumor, respectively. CONCLUSIONS: The results of this survey are reliable and representative due to large sampling and hospital-based data collection. The incidences of GTD decreased significantly compared with 1950s'. It is important to take pathological examination for GTD and to diagnose complate mole and partial mole correctly.

Twenty-five years' clinical experience with placental site trophoblastic tumors.

OBJECTIVE: To describe 34 cases of placental site trophoblastic tumor (PSTT) treated at Charing Cross Hospital over 25 years. STUDY DESIGN: Between 1975 and 2001, 1,685 patients with gestational trophoblastic disease (GTD) were treated; 34 of them had PSTT (2%). The computer database clinical notes and the pathology reports were accessed to obtain data on this patient group. The data were subsequently analyzed using Excel computer software. RESULTS: The mean age of the group was 33 years (95% CI 25-41). The antecedent pregnancy was a full-term, normal one in 18 cases (53%), a molar pregnancy in 7 (21%) and a missed abortion in 5 (15%). The mean interval from the last pregnancy to diagnosis was 3.4 years (95% CI 1.9-4.9). The range of serum hCG concentrations at diagnosis was 0-58,000, 79% with levels < 1,000 and 58% < 500. hCG was raised in all with active disease. The most frequent presenting complaint was vaginal bleeding, in 27 cases (79%). At diagnosis, the disease was localized to the uterus in 15 (44%); there was pelvic involvement in 8 (24%) and lung secondaries in 10 (29%). All seven deaths were disease related (21%); all had lung secondaries and presented more than four years since the last pregnancy. Excluding the seven deaths, the primary treatment was surgery alone in 10 cases (37%) (8 hysterectomies and 2 dilatation and curettages); 4 had surgery followed by adjuvant chemotherapy; 5 had neoadjuvant chemotherapy followed by surgery; 1 had chemotherapy alone, and the disease recurred and was successfully rechallenged; and 5 had surgery between chemotherapy cycles. The most common regimens consisted of EMA/CO and EP/EMA. CONCLUSION: Risk factors for death include lung metastatic involvement (50%) and an antecedent pregnancy interval of four years or more (100%). In contrast, those with no extrapelvic disease or a pregnancy interval of less than four years had 100% survival. In two-thirds of patients with disease limited to the uterus, surgery alone was curative. The WHO scoring system for GTD did not correlate with this outcome. Patients with PSTT should be managed separately from those with other types of GTD, as the disease behavior is different.

Epidemiology and time trends of gestational trophoblastic disease in Korea.

OBJECTIVES: For the purpose of determining the annual incidence and time trends of gestational trophoblastic disease (GTD), the medical records from 24 university hospitals, 13 private general hospitals and the Korean Research Institute of Gestational Trophoblastic Disease (KRI-TRD) were analyzed from 1971 to 1995. MATERIALS & RESULTS: From a total of 7198 GTD cases (H-mole=3831, Invasive mole=2163, Choriocarcinoma=1177, PSTr=27) among 838659 deliveries between 1971 and 1995, the hospital-based incidence of H-mole per 1000 deliveries declined from 40.2 during 1971-975, to 2.3 during 1991-995. The population-based incidence of H-mole, however, revealed an average of 2.05 per 1000 deliveries during 1991-995. Old age and gravidities as factors in GTD patients both decreased significantly during the study period. Time trends for the incidence of GTD in Korea revealed significant changes, not only a decrease in the incidence of GTD, but also an improvement in the annual remission rate. Korea's socio-eonomic improvement in recent decades also contributed to the decreased incidence of GTD and the increased survival rates.

Analysis of risk factors for postmolar trophoblastic disease: categorization of risk factors and effect of prophylactic chemotherapy.

Early identification of high risk molar pregnancy is important in preventing the development of subsequent postmolar trophoblastic disease (PMTD). In the present study, evaluation of risk factors of developing PMTD, and indications for initiating prophylactic chemotherapy, and investigation of the effects of prophylactic chemotherapy were undertaken. One hundred and forty complete molar pregnancies treated at Yonsei University College of Medicine were retrospectively analyzed. Thirty-six cases of PMTD developed in these molar pregnancies during follow-up. Risk factors for PMTD were ranked according to frequency with which they were associated with PMTD. The patients with no risk factors were classified in the low-risk group, with one or two in the medium-risk group, and with three or more in the high-risk group. Prophylactic chemotherapy was administered to 14 of 52 low-risk, to 21 of 46 medium-risk, and to 17 of 42 high-risk patients. Among the high-risk patients, the time required for remission was significantly shorter in the group with prophylactic chemotherapy (13.5 weeks) than in the group without prophylactic chemotherapy (22.4 weeks). There were no differences in the duration until remission among the low- and medium-risk patients. Of the 52 patients who received prophylactic chemotherapy, 8 (15.4%) developed PMTD. Among the high-risk patients the occurrence of PMTD was significantly lower in the prophylactic chemotherapy group. Among the low-risk and medium-risk patients, there were no differences in the occurrence of PMTD between the chemoprophylaxis treated and untreated groups. Our results strongly support the use of prophylactic chemotherapy for patients that were designed under our high risk criteria. Prophylactic chemotherapy helps to prevent or reduce the risk of developing PMTD, and shorten the time required for complete remission in high-risk patients.