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Background While chemotherapy is central to gestational trophoblastic disease (GTD) management, concerns over toxicity and resistance have renewed interest in hysterectomy. This study evaluated outcomes of patients treated with hysterectomy, focusing on histopathology, chemotherapy use, and survival. Methods A retrospective analysis was performed on consecutive eligible patients undergoing hysterectomy for GTD from 2014 to 2023. Data on demographics, surgery indications, chemotherapy, and follow-up were collected and analyzed. Results Among 96 GTD patients undergoing hysterectomy, the timing of surgery was a key determinant of treatment intensity. Patients who underwent first-line hysterectomy ( n  = 34) required significantly fewer chemotherapy cycles to achieve remission than those needing surgery after failed chemotherapy (non-first-line hysterectomy) (median: 2 [IQR: 1–4] vs. 7 [IQR: 5–9] cycles; P <0.001). This benefit was most evident in low-risk patients (WHO score 0–6), where primary surgery alone achieved cure in selected cases, thereby reducing or eliminating chemotherapy exposure. Hysterectomy was also definitive for chemoresistant histologies (placental site trophoblastic tumor and epithelioid trophoblastic tumor). The overall survival rate was 95% for the gestational trophoblastic neoplasia cohort. Conclusions This study demonstrates that first-line hysterectomy significantly reduces postoperative chemotherapy requirements for patients with GTD, particularly in the low-risk subgroup. These findings support integrating timely surgical intervention into risk-adapted treatment algorithms to de-escalate systemic therapy while maintaining high survival rates. For patients with chemoresistant histologies, hysterectomy remains a definitive therapeutic option.

Gestational trophoblastic disease encompasses a range of pregnancy-related disorders, consisting of the premalignant disorders of complete and partial hydatidiform mole, and the malignant disorders of invasive mole, choriocarcinoma, and the rare placental-site trophoblastic tumour. These malignant forms are termed gestational trophoblastic tumours or neoplasia. Improvements in management and follow-up protocols mean that overall cure rates can exceed 98% with fertility retention, whereas most women would have died from malignant disease 60 years ago. This success can be explained by the development of effective treatments, the use of human chorionic gonadotropin as a biomarker, and centralisation of care. We summarise strategies for management of gestational trophoblastic disease and address some of the controversies and future research directions.

Gestational trophoblastic diseases (GTD) encompass a spectrum of rare pre-malignant and malignant entities originating from trophoblastic tissue. This updated review will highlight important radiological features, pathology and classification, and provide insight into the clinical management of these uncommon disorders. There is a wide geographic variation with the incidence of hydatidiform mole varying between 0.57 and 2 per 1000 pregnancies. The use of ultrasound (US) in the management of early pregnancy symptoms and complications has positively impacted the earlier detection of these diseases and resulted in diminished morbidity. Additional imaging modalities are reserved for problem solving or assessment of pulmonary manifestations of molar pregnancy. Having an awareness of their pleomorphic sonographic presentation and additional pathology that can mimic GTD is critical to avoiding pitfalls. Histologic and molecular analysis further aids in differential diagnosis. Gestational trophoblastic neoplasia (GTN) is inclusive of all malignant GTDs, and arises after 20% of molar pregnancies but can also be seen with non-molar gestations. Biochemical monitoring with human chorionic gonadotrophin is imperative for ongoing monitoring and surveillance and allows early detection of this entity. Doppler US is used for confirmation of diagnosis with magnetic resonance imaging (MRI) reserved for problem solving or assessment of myometrial invasion. This is of heightened relevance in patients undergoing surgical management. Cross sectional imaging is reserved for patients in the setting of GTN for the purposes of staging, prognostication and in the setting of recurrent disease. This may require a combination of computed tomography, MRI and positron emission tomography. Doppler US can provide insight into chemotherapeutic response/predict resistance in patients with GTN. As our understanding of these disorders evolves, there has been maturation in management options with a shift from traditional chemotherapy to innovative immunotherapy, particularly in the setting of resistant or high-risk disease.

Background and purpose: Cure rates of gestational trophoblastic neoplasia (GTN) are excellent, however the surgical interventions in disease management are not well described. The primary aim of this study was to investigate the incidence and types of surgical procedures used for management of GTN and to report treatment outcomes in a population-based cohort. The secondary aim was to assess the impact of hysterectomy on time to human chorionic gonadotropin (hCG)-normalisation in low-risk GTN. Material and methods: Medical records of all patients treated for GTN at Karolinska University Hospital, Stockholm, Sweden between 1994 and 2020 were screened for treatment outcomes, types of surgical procedures and complications. Regression models were used to assess if hysterectomy affected time to complete remission in low-risk GTN. Results and interpretation: Over the 27-year study period, 185 patients with GTN were included. The primary complete remission rate was 98.4% and relapse rate 3.2%. Sixty-four patients (34.6%) underwent at least one surgical procedure; 39/154 (25.3%) of low-risk patients, 17/23 (73.9%) of high-risk patients and all (100%) patients with placental site or epithelioid trophoblastic tumour. No severe complications (Clavien-Dindo >3) were observed. Seven of 74 procedures (9.5%) were complicated by bleeding >1,000 mL or surgical site infection. Therapeutic hysterectomy significantly shortened time to hCG-normalisation in the low-risk group (48 vs 74 days, p = 0.002). This population-based study confirms the excellent cure rates and low relapse rates for GTN. Surgery plays an important role in the management of GTN with low risk of complications. Hysterectomy shortens time to hCG normalisation.

Introduction Atypical placental site nodule (APSN) is a rare diagnosis, representing remnants of a previous pregnancy and extravillous trophoblast tissue. These lesions are potential precursor lesions to rare forms of Gestational trophoblastic neoplasia (GTN). Recent data suggest up to a 15% risk of malignancy occurring either concurrently or manifesting within a few months of diagnosis. These patients are often young with future fertility considerations. Prognosis, treatment, and clinical follow‐up of APSN cases currently remain a matter of debate. This study aimed to address and explore some of these issues. Material and Methods Retrospective case series analysis was performed between 1st January 2000 and 31st December 2023 at the Sheffield Trophoblastic Disease Centre, Sheffield, UK. Patients on conservative management were asked at routine follow‐up telephone consultations if they would consider a completion hysterectomy in light of the risk of progression to GTN. Results Twenty‐two cases of APSN were registered, of which 10 (45%) received surgical management. Two (20%) cases were incidentally diagnosed following total abdominal hysterectomy (TAH) for other indications and eight (80%) had a TAH within twelve months of their initial diagnosis as part of primary management. None had histological evidence of GTN. Of the twelve (55%) patients initially opting primarily for conservative management, three (25%) decided to have a TAH performed based on the current evidence for risk of malignant transformation, eight (67%) indicated they would have a TAH based on advice from the center, and one (8%) was uncertain. No patients were diagnosed with GTN. Conclusions In this study, we found no evidence of malignant transformation in our patients, which conflicts with other published data conferring an 11%–14% risk of malignant transformation. An international consensus opinion needs to be reached within the Gestational trophoblastic community regarding the optimal advice, management, and follow‐up regimens for patients diagnosed with APSN. Retrospective series of 22 cases of atypical placental site nodule managed at a UK specialist trophoblastic disease center, revealing no cases of malignant conversion/Gestational trophoblastic neoplasia.

Investigations in recent decades have exploited tissue DNA genotyping as a powerful ancillary tool for the precision diagnosis and subclassification of gestational trophoblastic disease. As lesions of gestational origin, the inherited paternal genome, with or without copy number alterations, is the fundamental molecular basis for the diagnostic applications of DNA genotyping. Genotyping is now considered the gold standard in the confirmation and subtyping of sporadic hydatidiform moles. Although a precise diagnosis of partial mole requires DNA genotyping, prognostic stratification according to distinct genetic zygosity in complete moles has recently gained significant clinical relevance for patient care. Beyond hydatidiform moles, DNA genotyping has fundamental applications in the diagnosis or prognostic assessment of gestational trophoblastic tumors, in particular gestational choriocarcinoma. DNA genotyping provides a decisive tool in the separation of gestational trophoblastic neoplasia from non-gestational counterparts/mimics of either germ cell or somatic origin. The FIGO/WHO prognostic scoring scheme requires ascertaining the precise index gestational event and the time interval between the tumor and index gestation, where DNA genotyping can provide highly relevant information. With rapid acquisition of molecular diagnostic capabilities in the clinical practice, DNA genotyping has become closely integrated into the routine diagnostic workup of various forms of gestational trophoblastic disease.

Introduction Prophylactic chemotherapy (PC) has been suggested to be effective in prevention of post molar gestational trophoblastic neoplasia (PGTN) in patients with high-risk molar pregnancies. The goal of this study is to assess the efficacy of single dose methotrexate as PC in terms of spontaneous remission, time to remission, and progression to PGTN. Materials and methods Patients with molar pregnancy were recruited to the study and underwent cervical dilation and suction curettage. Patients who had pathologically proven complete hydatidiform mole were evaluated with abdominal ultrasonography to confirm complete evacuation and absence of remnants. These patients were allocated to two groups: group one received Methotrexate 50 mg/m2 via intramuscular injection, while group two did not. PGTN was defined according to the 2018 FIGO criteria. For patients with confirmed PGTN, the following variables were recorded: occurrence of metastasis, resistance to first-line chemotherapy and time to βHCG level normalization. Results Eighty patients were enrolled to the study, of which 22 cases (27.5%) received PC. It was found that PC with MTX did not significantly influence spontaneous remission (18 (81.8%) Vs 37 (63.7%), p value: 0.12) or time to remission (57 ± 22.5 Vs 61.24 ± 21.78 days, p value: 0.46) in high-risk molar pregnancies. Moreover, among patients in PC group and control group, 4 cases (18.2%) and 21 patients (36.3%) progressed to PGNT, respectively ( p value: 0.12). Although patients in PC group tended to be diagnosed in lower stages compared to patients in control group, this difference was insignificance ( p value: 0.95). Among patients who developed to PGTN, PC did not reduce the frequency of metastatic disease, resistance to first-line chemotherapy, or the time interval to serum βHCG level normalization (all p values > 0.05). Conclusion This study suggests that a single-dose MTX as PC may not be an effective therapeutic option for preventing PGTN in patients with high-risk molar pregnancy.

Gestational trophoblastic disease represents a spectrum of pregnancy related disorders, ranging from pre-malignant hydatidiform mole to malignant tumours, collectively referred to as gestational trophoblastic neoplasia. Gestational trophoblastic neoplasia includes malignant invasive mole, choriocarcinoma, and rare placental site trophoblastic and epithelioid trophoblastic tumours.1

Gestational trophoblastic disease is a rare complication of pregnancy that can develop into cancer. Medical outcomes of gestational trophoblastic disease are well researched, but the effect of the disease on health-related quality of life (HRQOL) requires attention if care is to be improved. This systematic review was designed to establish the effect of gestational trophoblastic disease and its treatment on HRQOL and to identify the appropriateness of HRQOL measures. Quantitative studies found HRQOL in long-term survivors of gestational trophoblastic disease to be at or above population norms. The disease had a negative effect on HRQOL for patients who experienced physical, psychological, and social sequelae related to the condition. Clinically significant levels of anxiety, depression, sexual dysfunction, and fertility-related distress were found in these patients. The results should be treated with caution because the evidence base was limited to small heterogeneous samples, data were retrospective, and a range of measures was used. Within qualitative studies on HRQOL for survivors of gestational trophoblastic disease, new conditions emerged, including nerve damage, fatigue, amenorrhoea, and grief. These areas are not captured in existing patient-reported outcome measures, and the content might not be valid for this population. Further qualitative research might lead to the development of a specific patient-reported outcome measure for gestational trophoblastic disease, providing reliable, meaningful, and valid assessments, and allowing longitudinal data to be obtained.

Gestational trophoblastic disease (GTD) is a heterogeneous group of rare tumours characterised by abnormal proliferation of trophoblastic tissue. It consists of benign or premalignant conditions, such as complete and partial molar pregnancy and variants of malignant diseases. The malignant tumours specifically are commonly referred to as gestational trophoblastic neoplasia (GTN). They consist of invasive mole, choriocarcinoma, placental-site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT). Patients with GTD are often asymptomatic, although vaginal bleeding is a common presenting symptom. With the advances in ultrasound imaging in early pregnancy, the diagnosis of molar pregnancy is most commonly made in the first trimester of pregnancy. Sometimes, additional imaging such as chest X-ray, CT or MRI can help detect metastatic disease. Most women can be cured, and their reproductive function can be preserved. In this review, we focus on the advances in management strategies for gestational trophoblastic disease as well as possible future research directions.