OBJECTIVE: To evaluate the association between gestational trophoblastic disease and the subsequent risk of developing non-trophoblastic cancer. METHODS: We conducted a retrospective cohort study of 3084 women with gestational trophoblastic disease and 1 415 812 women with obstetric deliveries in Quebec, Canada, between 1989 and 2021. The main exposure was gestational trophoblastic disease, including hydatidiform moles, invasive moles, and gestational choriocarcinoma. The outcome was development of non-trophoblastic cancer during 33 years of follow-up. We measured the association of gestational trophoblastic disease with non-trophoblastic cancer using adjusted hazard ratios (HR) and 95% confidence intervals (CI), and tested whether associations were stronger for certain types of cancer or cancers with later onset. RESULTS: The incidence of non-trophoblastic cancer was greater for women with invasive moles (47.1/10 000 person-years) and gestational choriocarcinoma (59.3/10 000 person-years) than hydatidiform moles (18.4/10 000 person-years) and no gestational trophoblastic disease (22.4/10 000 person-years). Gestational choriocarcinoma (HR 2.33, 95% CI: 1.35-4.01
P = 0.002) and invasive moles (HR 1.97, 95% CI: 1.06-3.65
P = 0.033) were associated with an elevated risk of non-trophoblastic cancer compared with no gestational trophoblastic disease, while hydatidiform moles were not. Gestational choriocarcinoma and invasive moles were mainly associated with gynecologic cancer. However, risk of cancer was limited to the short-term period after pregnancy and became similar to no gestational trophoblastic disease by the end of follow-up. CONCLUSION: While invasive moles and gestational choriocarcinoma appear to be associated with the subsequent development of non-trophoblastic cancer, the absolute risk is small and limited to the short-term.