Long-Term Follow-up of Women With Vaginal and Cervical Clear Cell Adenocarcinoma Associated With DES Exposure

Key Points

  • 5-year mortality was reduced among women with documented DES exposure vs those without, with 20-year mortality being similar in both groups.
  • Compared with the general population, mortality was 5 times higher among women aged 35 to 49 years with DES-associated clear cell adenocarcinoma. 

In a letter to the editor of The New England Journal of Medicine, Huo et al described long-term outcomes of women with vaginal and cervical clear cell adenocarcinoma associated with prenatal exposure to the synthetic nonsteroidal estrogen diethylstilbestrol (DES). As noted by the authors, women with DES-related clear cell adenocarcinoma are aging into their 50s and 60s, but the effect of this condition across their overall life span has not been well-defined.

Characteristics of Cohort

The report included a total of 695 women with clear cell adenocarcinoma in the Registry for Research on Hormonal Transplacental Carcinogenesis followed through 2014. Patients had a mean year of birth of 1955. Mean age at diagnosis was 22 years, with 80% of patients diagnosed between the ages of 15 and 30 years. Evidence of prenatal DES exposure was documented in 415 patients (60%).

Mortality Trends

A total of 219 patients died during median follow-up of 22.7 years, representing 20-year overall survival of 69%. Overall survival at 5 years was 86.1% in patients with documented prenatal DES exposure vs 81.2% among those without documented exposure; however, 20-year probability of survival was similar in the 2 groups. In analysis adjusting for tumor stage, histologic type, and age, the adjusted hazard ratio for mortality for the documented vs nondocumented group was 0.63 (95% confidence interval [CI] =0.42–0.94) for ≤ 5 years and 0.89 (95% CI= 0.59–1.35) for > 5 years. 

Patients with clear cell adenocarcinoma had greater mortality risk across their life span. Compared with the general US population, risk of death among women with DES-related clear cell adenocarcinoma was 27 times higher for women aged between 10 and 34 years, 5 times higher for those aged 35 to 49 years, and 2 times higher for those age 50 to 65 years.

The authors noted that the excess mortality risk among patients aged 35 to 49 years mainly reflected late recurrences, whereas the excess risk after age 50 years might reflect additional life-threatening conditions among women with prenatal exposure to DES. They concluded, “It is therefore important to continue the surveillance of this unique cohort of patients with DES-related clear cell adenocarcinoma to examine their health conditions late in life.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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