OBJECTIVE: To evaluate the efficacy of actinomycin D (ActD) as prophylactic chemotherapy (P-chem) in patients with high-risk complete hydatidiform mole (Hr-CHM) on progression to gestational trophoblastic neoplasia (GTN). METHODS: From 1996 to 2023, 426 Hr-CHMs were selected in a cohort of 1623 patients with gestational trophoblastic disease (GTD). From 1996 to 2023, 290 patients with Hr-CHMs received a single bolus dose of Act-D at the time of uterine evacuation (Hr-CHM P-chem group)
136 with the same risk factors did not receive P-chem (Hr-CHM control group). The variables assessed in post-molar GTN were incidence and morbidity considering hCG serum level at diagnosis, relapse frequency, hysterectomy rates. RESULTS: Post-molar GTN was diagnosed in 19 % of the patients with Hr-CHM P-Chem (55/290) and in 39.7 % of the patients in the Hr-CHM control group (54/136) (P <
0.001). The relative risk of developing post-molar GTN decreased by 52 % (RR = 0.48
95 % CI: 0.35-0.66
P <
0.001), with a number needed to treat (NNT) of 5. Patients in the P-chem group had a lower hCG serum level (P = 0.007), lower risk of recurrence (P = 0.001) and lower risk of hysterectomy (P = 0.04), with no effect on time to GTN diagnosis (P = 0.09), first line chemotherapy response (P = 0.50) and time to remission (P = 0.72). CONCLUSION: A single bolus dose of Act-D (1.25 mg/m2) given as P-chem during uterine evacuation in patients with Hr-CHM may safely prevent the incidence of post-molar GTN and reduce the morbidity associated with GTN. This prophylactic approach can be adopted at any trophoblastic disease center (TDC).