Abstract 709: Incidence and mortality of diethylstilbestrol-related clear-cell adenocarcinoma of the vagina and cervix: 40 years of long-term follow-up

Abstract

Abstract Objective: Women exposed to diethylstilbestrol (DES) in utero are at increased risk for the development of vaginal and cervical clear cell adenocarcinoma (CCA), and possibly of breast cancer, diabetes, and cardiovascular diseases as well. A peak in the age-incidence curve in DES- related CCA has been documented at ages 19 to 24. It is unknown if a second peak will occur in later life, the ages when CCA developed spontaneously in the pre-DES era. In addition, the long-term prognosis and health impact for adolescents and young adults who have DES-related CCA are unknown. Methods: 720 cases of CCA were reviewed from the CCA Registry at the University of Chicago through 2014. Rates and cumulative risks for CCA were calculated based on white women born in the U.S. from 1948 through 1971. Kaplan-Meier method was used to estimate survival probability among women with CCA. Cox models were used to identify independent prognostic factors. To gauge the relative impact of young-onset clear-cell adenocarcinoma on mortality, we compared their mortality hazards with mortality hazards of the U.S. female population, and calculated standardized mortality ratio (SMR). Results: In 420 CCA cases there was documented evidence of prenatal DES exposure. 80% patients had a CCA between ages 15 and 31 but some occurred as late as age 55. A small second peak occurred around age 40. The risk of U.S. born, white DES-related CCA was highest in the 1951-1956 birth cohort, and this birth cohort effect correlated with DES use in the U.S. By age 50, the cumulative risk of CCA was 1 per 750 exposed women. A total of 695 CCA patients were included in the survival analysis. After a median follow-up of 22.7 years (interquartile range: 10.8-35.1 years), 219 patients died. The 5-year, 10-year, and 20-year survival probabilities were 83%, 75%, and 69%, respectively. As expected, tumor stage was a strong prognostic factor for survival among DES-related CCA cases. Tubular-cystic histology was associated with better survival compared with papillary, solid, or a combination of these histological patterns. Adolescent patients (<18 years old) had worse survival than young adult patients. Compared with general U.S. female population, women with DES-related CCA had 27-fold increased risk of death between 10 and 35 year of age (SMR 27.06, 95% CI: 23.04-31.58), 5-fold increased risk between 35 and 50 year of age (SMR 5.07, 95% CI: 3.59-6.95), 2-fold increased risk after age 50 (SMR 2.03, 95% CI: 1.22-3.18). Conclusion: Our study drew a relatively complete epidemic curve of DES-related CCA. There existed late-onset CCA among women with prenatal exposure of DES. DES-related CCA increased mortality not only during early life among exposed women, but also impacted life after age 50. These results suggest continued close health follow-up of this population. Citation Format: Dezheng Huo, Diane Anderson, Arthur L. Herbst. Incidence and mortality of diethylstilbestrol-related clear-cell adenocarcinoma of the vagina and cervix: 40 years of long-term follow-up [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 709. doi:10.1158/1538-7445.AM2017-709