Primary adenocarcinoma of the vagina not associated with diethylstilbestrol (DES) exposure

Objective.: Primary non-diethylstilbestrol (DES)-associated adenocarcinoma of the vagina (NDAV) is a rare entity that has not been well described. The purpose of this study was to define the pathologic characteristics of verified NDAV and characterize the outcomes of patients who present with this rare malignancy. Methods.: The tumors of all patients treated with definitive radiation therapy for NDAV between 1970 and 2000 were centrally reviewed. Data regarding patient, tumor, and treatment characteristics were abstracted from the hospital records of each patient. Survival rates were calculated and outcomes of patients with NDAV were compared with those of patients with squamous cell carcinoma (SCC) of the vagina treated similarly over the same period. Results.: Twenty-six patients with a median age of 54 years had primary NDAV confirmed by central pathologic review. Twenty patients (77%) were treated with external-beam radiation therapy (EBRT) followed by brachytherapy, and six patients (23%) were treated with EBRT alone. At 5 years, the overall survival rates of patients with NDAV and SCC were 34% and 58%, respectively (p < 0.01). Patients with NDAV had a significantly worse pelvic disease control rate than patients with SCC (31% vs. 81%; p < 0.01). At 5 years, 39% of patients with NDAV and 15% with SCC had developed distant metastasis (p < 0.01). Conclusions.: Primary NDAV is a rare disease with a poor prognosis. Patients with this disease have significantly worse outcomes than do patients with SCC, and chemotherapy or novel systemic biologic agents may be needed to achieve higher cure rates.