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.


RESULTS
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%.


CONCLUSIONS
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.


BACKGROUND
National Commissioning Group.
Schmid
Peter
P
Imperial College London, UK. p.schmid@imperial.ac.uk
Nagai
Yutaka
Y
Agarwal
Roshan
R
Hancock
Barry
B
Savage
Philip M
PM
Sebire
Neil J
NJ
Lindsay
Iain
I
Wells
Michael
M
Fisher
Rosemary A
RA
Short
Delia
D
Newlands
Edward S
ES
Wischnewsky
Manfred B
MB
Seckl
Michael J
MJ
D000328:Adult; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000378:metabolism; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D003609:Dactinomycin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007044:Hysterectomy; D053208:Kaplan-Meier Estimate; D008727:Methotrexate / Q000627:therapeutic use; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011247:Pregnancy; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D018245:Trophoblastic Tumor, Placental Site / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D006113:United Kingdom / Q000453:epidemiology; D014594:Uterine Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D014750:Vincristine / Q000627:therapeutic use
D014408:Biomarkers, Tumor; D006063:Chorionic Gonadotropin; D003609:Dactinomycin; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D008727:Methotrexate