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

Abstract

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.

Fig. 1

Treatment overview Flow chart demonstrating treatment and response of all 125 patients included. CR, complete response as defined by normalisation of hCG and no evidence of residual disease on imaging or no evidence of malignancy in resected residual masses

Fig. 2

Overall survival by stage (a) and antecedent pregnancy (b). The numbers of events at 10 years for stages I, II, III and IV disease were 5, 3, 9 and 8, respectively. The number of events at 10 years for an antecedent pregnancy <48 months and ≥48 months was 4 versus 21

Fig. 3

Overall survival by patient cohort for all patients included (a) and for patients with an antecedent pregnancy of ≥ 48 months (b). The number of events at 10 years was 15 for the 1976–2006 cohort versus 10 for the 2007–2014 cohort. For patients with an antecedent pregnancy of ≥48 months, the number of events at 10 years was 13 versus 8 in the first (1976–2006) and second (2007–2014) cohort, respectively

Fig. 4

Recommended stage-adapted and personalised treatment approach. Schematic overview of treatment recommendation per FIGO stage. TAH total abdominal hysterectomy; EP/EMA etoposide, cisplatin alternated with etoposide, methotrexate, actinomycin-D