Florence Couder1, Jérôme Massardier2, Benoît You3, Fatima Abbas4, Touria Hajri5, Jean-Pierre Lotz6, Anne-Marie Schott7, François Golfier8. 1. Service de Gynécologie-Obstétrique et de Chirurgie Oncologique du Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Faculté de Médecine Lyon Sud, Université Lyon 1, France. 2. Centre de Référence des Maladies Trophoblastiques de Lyon, Faculté de Médecine Lyon Sud, Université Lyon 1, France; Service d'Obstétrique, Centre Hospitalier Femme-Mère-Enfant, Hospices Civils de Lyon, Université Lyon 1, France. 3. Centre de Référence des Maladies Trophoblastiques de Lyon, Faculté de Médecine Lyon Sud, Université Lyon 1, France; Service d'Oncologie Médicale, CITOHL, Service d'Hématologie, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Faculté de Médecine Lyon Sud, Université Lyon 1, France. 4. Université de Lyon, Hospices Civils de Lyon, HESPER, France. 5. Centre de Référence des Maladies Trophoblastiques de Lyon, Faculté de Médecine Lyon Sud, Université Lyon 1, France. 6. Centre de Référence des Maladies Trophoblastiques de Lyon, Faculté de Médecine Lyon Sud, Université Lyon 1, France; Service d'Oncologie, Centre Hospitalier Tenon, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, France. 7. Centre de Référence des Maladies Trophoblastiques de Lyon, Faculté de Médecine Lyon Sud, Université Lyon 1, France; Université de Lyon, Hospices Civils de Lyon, HESPER, France. 8. Service de Gynécologie-Obstétrique et de Chirurgie Oncologique du Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Faculté de Médecine Lyon Sud, Université Lyon 1, France; Centre de Référence des Maladies Trophoblastiques de Lyon, Faculté de Médecine Lyon Sud, Université Lyon 1, France.
Abstract
BACKGROUND: Patients with 2000 FIGO low-risk gestational trophoblastic neoplasia are commonly treated with single-agent chemotherapy. Methotrexate is widely used in this indication in Europe. Analysis of relapse after treatment and identification of factors associated with relapse would help understand their potential impacts on 2000 FIGO score evolution and chemotherapy management of gestational trophoblastic neoplasia patients. OBJECTIVE: This retrospective study analyzes the predictive factors of relapse in low-risk gestational trophoblastic neoplasia patients whose hormone chorionic gonadotropin (hCG) normalized with methotrexate alone. STUDY DESIGN: Between 1999 and 2014, 993 patients with gestational trophoblastic neoplasia were identified in the French Trophoblastic Disease Reference Center database, of which 465 were low-risk patients whose hCG normalized with methotrexate alone. Using univariate and multivariate analysis we identified significant predictive factors for relapse after methotrexate. The Kaplan-Meier method was used to plot the outcome of patients. RESULTS: The 5-year recurrence rate of low-risk gestational trophoblastic neoplasia patients whose hCG normalized with methotrexate alone was 5.7% (confidence interval [IC], 3.86-8.46). Univariate analysis identified an antecedent pregnancy resulting in a delivery (HR = 5.96; 95% CI, 1.40-25.4, P = .016), a number of methotrexate courses superior to 5 courses (5-8 courses vs 1-4: HR = 6.19; 95% CI, 1.43-26.8, P = .015; 9 courses and more vs 1-4: HR = 6.80; 95% CI, 1.32-35.1, P = .022), and hCG normalization delay centered to the mean as predictive factors of recurrence (HR = 1.27; 95% CI, 1.09-1.49, P = .003). Multivariate analysis confirmed the type of antecedent pregnancy and the number of methotrexate courses as independent predictive factors of recurrence. A low-risk gestational trophoblastic neoplasia arising after a normal delivery had an 8.66 times higher relapse risk than that of a postmole gestational trophoblastic neoplasia (95% CI, 1.98-37.9], P = .0042). A patient who received 5-8 courses of methotrexate had a 6.7 times higher relapse risk than a patient who received 1-4 courses (95% CI, 1.54-29.2, P = .011). A patient who received 9 courses or more had an 8.1 times higher relapse risk than a patient who received 1-4 courses of methotrexate (95% CI, 1.54-42.6, P = .014). CONCLUSION: Low-risk gestational trophoblastic neoplasia following a delivery and patients who need more than 4 courses of methotrexate to normalization are at a higher risk of relapse than other low-risk patients. Allotting a higher score to the "antecedent pregnancy" FIGO item should be considered for postdelivery gestational trophoblastic neoplasia. Further analysis of the need for consolidation courses is warranted.
BACKGROUND:Patients with 2000 FIGO low-risk gestational trophoblastic neoplasia are commonly treated with single-agent chemotherapy. Methotrexate is widely used in this indication in Europe. Analysis of relapse after treatment and identification of factors associated with relapse would help understand their potential impacts on 2000 FIGO score evolution and chemotherapy management of gestational trophoblastic neoplasiapatients. OBJECTIVE: This retrospective study analyzes the predictive factors of relapse in low-risk gestational trophoblastic neoplasiapatients whose hormone chorionic gonadotropin (hCG) normalized with methotrexate alone. STUDY DESIGN: Between 1999 and 2014, 993 patients with gestational trophoblastic neoplasia were identified in the French Trophoblastic Disease Reference Center database, of which 465 were low-risk patients whose hCG normalized with methotrexate alone. Using univariate and multivariate analysis we identified significant predictive factors for relapse after methotrexate. The Kaplan-Meier method was used to plot the outcome of patients. RESULTS: The 5-year recurrence rate of low-risk gestational trophoblastic neoplasiapatients whose hCG normalized with methotrexate alone was 5.7% (confidence interval [IC], 3.86-8.46). Univariate analysis identified an antecedent pregnancy resulting in a delivery (HR = 5.96; 95% CI, 1.40-25.4, P = .016), a number of methotrexate courses superior to 5 courses (5-8 courses vs 1-4: HR = 6.19; 95% CI, 1.43-26.8, P = .015; 9 courses and more vs 1-4: HR = 6.80; 95% CI, 1.32-35.1, P = .022), and hCG normalization delay centered to the mean as predictive factors of recurrence (HR = 1.27; 95% CI, 1.09-1.49, P = .003). Multivariate analysis confirmed the type of antecedent pregnancy and the number of methotrexate courses as independent predictive factors of recurrence. A low-risk gestational trophoblastic neoplasia arising after a normal delivery had an 8.66 times higher relapse risk than that of a postmole gestational trophoblastic neoplasia (95% CI, 1.98-37.9], P = .0042). A patient who received 5-8 courses of methotrexate had a 6.7 times higher relapse risk than a patient who received 1-4 courses (95% CI, 1.54-29.2, P = .011). A patient who received 9 courses or more had an 8.1 times higher relapse risk than a patient who received 1-4 courses of methotrexate (95% CI, 1.54-42.6, P = .014). CONCLUSION: Low-risk gestational trophoblastic neoplasia following a delivery and patients who need more than 4 courses of methotrexate to normalization are at a higher risk of relapse than other low-risk patients. Allotting a higher score to the "antecedent pregnancy" FIGO item should be considered for postdelivery gestational trophoblastic neoplasia. Further analysis of the need for consolidation courses is warranted.
Authors: Mariza Branco-Silva; Izildinha Maesta; Kevin Elias; Ross Stuart Berkowitz; Joelcio Francisco Abbade; Neil S Horowitz Journal: BMJ Open Date: 2022-02-24 Impact factor: 2.692