Intensified therapies improve survival and identification of novel prognostic factors for placental-site and epithelioid trophoblastic tumours.

BACKGROUND: Placental-site trophoblastic (PSTT) and epithelioid trophoblastic tumours (ETT) are the rarest malignant forms of gestational trophoblastic disease (GTD). Our prior work demonstrated that an interval of ≥48 months from the antecedent pregnancy was associated with 100% death rate, independent of the stage. Here, we assess whether modified treatments for these patients have increased survival and identify new prognostic factors. METHODS: The United Kingdom GTD database was screened to identify all PSTT/ETT cases diagnosed between 1973 and 2014. Data and survival outcomes from our prior patient cohort (1976-2006) were compared to our new modern cohort (2007-2014), when intensified treatments were introduced. RESULTS: Of 54,743 GTD patients, 125 (0.23%) were diagnosed with PSTT and/or ETT. Probability of survival at 5 and 10 years following treatment was 80% (95% CI 72.8-87.6%) and 75% (95% CI 66.3-84.3%), respectively. Univariate analysis identified five prognostic factors for reduced overall survival (age, FIGO stage, time since antecedent pregnancy, hCG level, mitotic index) of which stage IV disease (HR 6.18, 95% CI 1.61-23.81, p = 0.008) and interval ≥48 months since antecedent pregnancy (HR 14.57, 95% CI 4.17-50.96, p < 0.001) were most significant on multivariable analysis. No significant differences in prognostic factors were seen between the old and new patient cohort. However, the new cohort received significantly more cisplatin-based and high-dose chemotherapy, and patients with an interval ≥48 months demonstrated an improved median overall survival (8.3 years, 95% CI 1.53-15.1, versus 2.6 years, 95% CI 0.73-4.44, p = 0.·005). CONCLUSION: PSTT/ETT with advanced FIGO stage or an interval ≥48 months from their last known pregnancy have poorer outcomes. Platinum-based and high-dose chemotherapy may help to improve survival in poor-prognosis patients.

Postoperative chemotherapy on placental site trophoblastic tumor in early stage: analysis of 60 cases.

PURPOSE OF INVESTIGATION: To review the literature of placental site trophoblastic tumor (PSTT) and explore the effect of postoperative chemotherapy in patients with Stage I. MATERIALS AND METHODS: The authors searched literature on Medline, Excerpta Medica Database (EMBASE), and other resources using the keywords "placental site trophoblastic tumor" and "PSTT" from 1981 ito 2014. RESULTS: A total number of 60 patients with Stage I disease were identified, and the presentation, treatment, tumor response, disease status, and follow-up were retrieved and reviewed. According to the authors' knowledge, 725 cases associated with PSTT have been reported in 29 nations/areas since 1981. In this series, the probability of overall survival at ten years in the group of surgery alone and postoperative chemotherapy were 96.7% and 79.1% (p = 0.199), and recurrence-free survival rates were 91.8% and 63.3%, respectively. CONCLUSION: The benefit from postoperative chemotherapy is still equivocal. There is a need for scrupulousness before adding postoperative chemotherapy.

Nonchoriocarcinomatous Trophoblastic Tumors of the Testis: The Widening Spectrum of Trophoblastic Neoplasia.

Tumors of trophoblastic derivation other than choriocarcinoma are very rare in the testis but have been reported on occasion in association with other germ cell tumors. Their morphologic spectrum is analogous to the trophoblastic tumors of the female genital tract including epithelioid trophoblastic tumor (ETT) and placental site trophoblastic tumor (PSTT). Herein we report our experience with 8 cases of trophoblastic tumors of testicular origin that lacked the features of choriocarcinoma; these included 4 ETTs, 1 PSTT, 1 unclassified trophoblastic tumor (UTT), 1 partially regressed choriocarcinoma with a monophasic morphology, and 1 hybrid tumor showing a mixture of adenocarcinoma and a UTT. All tumors occurred in young men 19 to 43 years old. Five arose de novo within the testis (2 ETTs, 1 UTT, 1 regressing choriocarcinoma, and the hybrid tumor) as a component of mixed germ cell tumors, and 3 (2 ETTs and 1 PSTT) were found in metastatic sites after chemotherapy. The trophoblastic component was minor (5% to 10%) in 6 tumors but was 95% of 1 metastatic tumor (ETT) and 50% of the hybrid tumor. Other germ cell tumor elements were identified in all cases, most commonly teratoma. The ETTs consisted of nodules and nests of squamoid trophoblast cells showing abundant eosinophilic cytoplasm, frequent apoptotic cells, extracellular fibrinoid material, and positivity for p63 and negativity for human placental lactogen (HPL). The PSTT showed sheets of discohesive, pleomorphic, mononucleated trophoblast cells that invaded blood vessels with fibrinoid change and were p63 negative and HPL positive. The UTT showed a spectrum of small and large trophoblast cells, some multinucleated but lacking distinct syncytiotrophoblasts, and was patchily positive for both p63 and HPL. The hybrid tumor had ETT-like and adenocarcinomatous areas that coexpressed inhibin and GATA3 but were negative for p63 and HPL, leading to classification of the trophoblastic component as UTT. Seven of the patients were alive and well on follow-up (8 to 96 mo; median, 39 mo), whereas the patient with the hybrid tumor died of liver metastases at 2 years. Our study verifies that trophoblastic neoplasms often having the features of nonchoriocarcinomatous gestational trophoblastic tumors may arise from the testis, occur either in the untreated primary tumor or in metastases after chemotherapy, and should be distinguished from choriocarcinoma given what appears to be a less aggressive clinical course.

Retrospective analysis of the clinicopathologic and prognostic characteristics of stage I placental site trophoblastic tumor in China.

OBJECTIVE: To investigate clinicopathologic features and identify prognostic factors of placental site trophoblastic tumor (PSTT). METHODS: In a retrospective study, data were analyzed from patients with stage I PSTT treated at a tertiary hospital in Shanghai, China, from January 2007 to May 2013. Univariate log-rank tests were used to examine the association between clinicopathologic characteristics and overall survival and disease-free survival (DFS). RESULTS: In total, seven patients had stage I PSTT. Mean age was 31.6 years (range 22-42). Four patients had term delivery as the outcome of their antecedent pregnancy. Six had a ß-human chorionic gonadotropin (ß-hCG) serum concentration of less than 10 000 mIU/mL. Among five patients who underwent hysterectomy combined with chemotherapy, one had recurrent disease. One patient received fertility-preserving therapy and achieved complete remission. The mean 5-year overall survival and DFS were 100% and 86%, respectively. Maximum ß-HCG concentration of at least 10 000 mIU/mL and a mitotic index of more than 5 mitotic counts per 10 high-power fields were associated with disease recurrence (both P=0.014). CONCLUSION: Pretreatment ß-hCG concentration and mitotic index might be predictors of recurrence among patients with PSTT. Fertility-preserving therapy might be practical in some patients.

Placental site trophoblastic tumor: report of a tertiary center experience.

OBJECTIVE: To analyze the clinical and pathological characteristics of placental site trophoblastic tumor (PSTT) cases and to discuss the diagnosis, treatment, and prognosis of PSTT. MATERIALS AND METHODS: The clinical and pathological data of eight patients with PSTT at Istanbul Medical Faculty Hospital from 1988 to 2010 were analyzed retrospectively. RESULTS: The mean age of the patients was 31 years. The antecedent pregnancy was full-term delivery in most of the patients (6/8, 75%). The mean interval from last pregnancy to diagnosis of PSTT was 35 months (range, six to 192). Serum human chorionic gonadotropin (hCG) levels at the time of diagnosis ranged from 0.1 to 2280 mIU/ml (mean, 614). All patients had Stage 1 disease and ultimately underwent hysterectomy. None of the patients received adjuvant chemotherapy. One patient died of an unknown reason, one month after the surgery. The rest of the patients were alive and without evidence of disease after an average of 3.5 years (range, one to 11) of follow-up. CONCLUSION: Hysterectomy alone can provide long-term survival in early-stage disease.

Worldwide survey of the results of treating gestational trophoblastic disease.

OBJECTIVE: To determine factors influencing outcome for patients with gestational trophoblastic disease (GTD) from throughout the world. STUDY DESIGN: Physicians known to treat GTD were sent a questionnaire. RESULTS: There were 32 responses from 17 countries, totaling 26,153 patients. Of 14,093 patients with complete mole 20.6% developed trophoblastic neoplasia, and 5.7% died. There were 10,230 patients with partial mole, of whom 6.5% received therapy for neoplasia. There were 548 patients with post-term pregnancy choriocarcinoma, of whom 13.4% died. Of 137 patients with placental site trophoblastic tumor 16.1% died. The remaining 1,165 patients did not fit into a designated diagnostic category. The mortality rate for 2,818 patients with GTD primarily treated at a trophoblast center was 2.1%, as compared with 8% among 1,854 patients referred after failure of primary treatment (p < 0.01). CONCLUSION: Patients treated by physicians experienced in the management of trophoblastic disease have better results and survival.

Long-term outcome of placental site trophoblastic tumor in The Netherlands.

OBJECTIVE: To evaluate the outcome of 16 cases of placental site trophoblastic tumors (PSTTs) treated throughout The Netherlands. STUDY DESIGN: Patients with PSTT between 1991 and 2009 were identified using the nationwide network and registry of histopathology and cytopathology in The Netherlands (PALGA) and medical records. RESULTS: Data for 16 patients could be retrieved. The median age of the patients was 32 years. In 7 cases the antecedent pregnancy was a miscarriage and in 6, a term delivery. Clinical data on 3 patients could not be retrieved. Six patients were low-risk according to the International Federation of Gynecology and Obstetrics staging system. The median human chorionic gonadotropin (hCG) level was 46 IU/L, but in 4 patients the hCG level was not elevated. In the majority of patients a hysterectomy was performed, and 5 patients needed additional chemotherapy. There was only 1 recurrence and there were no fatalities. CONCLUSION: This study emphasizes the need for an international registration. No fatalities were registered. Because of the low incidence and limited experience of general gynecologists with this disease, there is a preference for centralization of all patients with PSTT regardless of their stage.

Placental site trophoblastic tumor: analysis of presentation, treatment, and outcome.

OBJECTIVE: Placental-site trophoblastic tumor (PSTT) is the rarest form of gestational trophoblastic disease (GTD). A risk-adapted treatment approach has been advocated, but controversy exists as to the most important prognostic markers for this disease. Our goal was to determine the prognostic markers for patients with PSTT seen at our center. METHODS: We conducted a retrospective analysis of patients with PSTT seen at a single tertiary care center between 1996 and 2011. The association of FIGO stage, interval from antecedent pregnancy, antecedent pregnancy outcome, human chorionic gonadotropin (hCG) level, and age to overall survival was examined using univariate log-rank tests. Presentation, treatment, and outcome were summarized using descriptive statistics. RESULTS: Data from 17 patients were analyzed. Eight (47%) had Stage I/II disease and 9 (53%) had Stage III/IV disease. Median overall survival for the entire cohort was 86 months (range, 2-101 months). Median duration of follow-up for surviving patients was 56 months. Increasing FIGO stage (I-III versus IV) was associated with a worse overall survival (p=0.009). Interval from antecedent pregnancy (≥12months), antecedent pregnancy outcome (full-term), hCG (≥1000 IU/L), and age (≥40) were not associated with worse survival. CONCLUSION: FIGO stage, specifically Stage IV disease, was the most important predictor of overall survival in our cohort of PSTT patients.

Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study.

BACKGROUND: Placental-site trophoblastic tumours are a rare form of gestational trophoblastic disease and consequently information about optimum management or prognostic factors is restricted. We aimed to assess the long-term outcome of stage-adapted management by surgery, chemotherapy, or both for patients with the disorder. METHODS: 35 550 women were registered with gestational trophoblastic disease in the UK (1976-2006), of whom 62 were diagnosed with placental-site trophoblastic tumours and included, retrospectively, in the study. Patients were treated by surgery, chemotherapy, or both. We estimated the probabilities of overall survival and survival without recurrence of disease 5 and 10 years after the date of first treatment, and calculated the association of these endpoints with prognostic factors, including time since antecedent pregnancy, serum concentration of beta-human chorionic gonadotropin, and stage of disease, with both univariate and multivariate analyses. FINDINGS: Probabilities of overall and recurrence-free survival 10 years after first treatment were 70% (95% CI 54-82) and 73% (54-85), respectively. Patients with stage I disease had a 10-year probability of overall survival of 90% (77-100) and did not benefit from postoperative chemotherapy. By contrast, patients with stage II, III, and IV disease required combined treatment with surgery and chemotherapy; probability of overall survival at 10 years was 52% (3-100) for patients with stage II disease and 49% (26-72) for stage III or IV disease. Outcome for patients who had recurrent or refractory disease was poor: only four (22%) patients achieved long-term survival beyond 60 months. Multivariate analysis showed that the only significant independent predictor of overall and recurrence-free survival was time since antecedent pregnancy. A cutoff point of 48 months since antecedent pregnancy could differentiate between patients' probability of survival (<48 months) or death (>/=48 months) with 93% specificity and 100% sensitivity, and with a positive predictive value of 100% and a negative predictive value of 98%. INTERPRETATION: Stage-adapted management with surgery for stage I disease, and combined surgery and chemotherapy for stage II, III, and IV disease could improve the effectiveness of treatment for placental-site trophoblastic tumours. Use of 48 months since antecedent pregnancy as a prognostic indicator of survival could help select patients for risk-adapted treatment. FUNDING: National Commissioning Group.