NATURAL HISTORY OF VAGINAL CANCER

June 9, 2009 — Stage, tumor size, histologic features, and treatment modality are associated with an increased risk for mortality from vaginal cancer, according to the results of a study reported in the May issue of Obstetrics & Gynecology.

"Recognized factors that increase a woman's lifetime risk of vaginal cancer include younger age at coitarche, greater number of lifetime sexual partners, smoking, in utero diethylstilbestrol exposure, and human papillomavirus (HPV) infection," write Chirag A. Shah, MD, MPH, from the University of Washington in Seattle, and colleagues. "The cause of vaginal cancer is closely linked to cervical cancer, and HPV infection seems to be a necessary cofactor in most cases."

The goal of this study was to assess the current effect on mortality of demographic factors, pathologic characteristics of the tumor, and choice of treatment in women with vaginal cancer. The investigators identified 2149 women diagnosed with primary vaginal cancer between 1990 and 2004, using data from 17 population-based cancer registries participating in the Surveillance, Epidemiology, and End Results program. Cox proportional hazards modeling was used to determine the association between various demographic factors, tumor characteristics, and treatments and risk for vaginal cancer mortality.

At diagnosis, mean age was 65.7 ± 14.3 years, and approximately two thirds were non-Hispanic whites. However, African American women had the highest incidence of vaginal cancer (1.24 per 100,000 person-years). Higher stage predicted lower 5-year disease-specific survival duration, which was 84% for stage I, 75% for stage II, and 57% for stage III/IV. The risks for mortality were increased for tumor size greater than 4 cm (hazard ratio [HR], 1.71) and for advanced disease (HR, 4.67), as determined in a multivariate adjusted model.

Women with vaginal melanoma had a 1.51-fold increased risk for mortality vs those who had squamous cell carcinomas (95% confidence interval, 1.07 - 2.41). In treatment modality, surgery alone had the lowest risk for mortality. Compared with women diagnosed from 1990 to 1994, those diagnosed after 2000 had an adjusted 17% decrease in their risk for death, suggesting a decrease in risk of mortality with time.

"Stage, tumor size, histology, and treatment modality significantly affect a woman's risk of mortality from vaginal cancer," the study authors write. "There seems to be a survival advantage that is temporally related to the advent of chemoradiation."

Limitations of this study include observational design, use of data that had already been collected, missing data on tumor size for more than half of cases, lack of data on chemotherapy, and possible residual confounding by unmeasured predictors.

"When possible in early stage disease, surgery seems to confer a survival advantage," the study authors conclude. "The decision on treatment modality must still be made in the context of the individual patient, because it is unlikely that prospective trials will be undertaken to answer this specific question. In the future we may be able to see if the trend of decreased mortality with modern treatment continues; but presently, it seems there may be an ongoing reduction in the risk of mortality associated with the use of chemoradiation in women with vaginal cancer."

• 2694 women with primary vaginal cancer were identified from 17 population-based US cancer registries in the Surveillance, Epidemiology, and End Results program.
• 2531 patients diagnosed between January 1990 and November 2004 without a history of in situ or invasive cancer were eligible for analysis.
• The final multivariate analysis included 2149 cases of invasive vaginal cancer.
• Exclusion criteria were age younger than 20 years or older than 89 years and vaginal carcinoma in situ.
• Follow-up period started with the date of diagnosis and ended with the date of death, last known date of living, or end of study.
• The primary outcome measure was death from vaginal cancer.
• Factors evaluated for a relationship with mortality risk included age at diagnosis, year of diagnosis, ethnicity, socioeconomic status, histologic tumor type, American Joint Committee on Cancer stage, grade, tumor size, lymph node status, and treatment method.
• Multivariate analysis adjusted for age, year of diagnosis, stage, and treatment.
• Mean age at diagnosis was 65.7 years (SD, 14.3 years).
• Most women were non-Hispanic whites (66%), with the remainder being African Americans (14%), Hispanic whites (12%), Asian or Pacific Islanders (7%), and others (1%).
• Stage I was the most common, occurring in 36%.
• Most women (65%) had squamous-type histologic features.
• The incidence rate of vaginal cancer per 100,000 person-years increased with age (4.43 in ages 80 - 89 years vs 0.03 in ages 20 - 29 years).
• The vaginal cancer incidence rate per 100,000 person-years was highest in African Americans and lowest in Asians or Pacific Islanders (1.24 vs 0.64).
• The vaginal cancer incidence rate per 100,000 person-years was highest in metropolitan Detroit and lowest in Utah (1.32 vs 0.56).
• Kaplan-Meier curves showed the 5-year disease-specific survival rate was 84% for stage I tumors, 75% for stage II tumors, and 57% for stage III or IV tumors.
• 5-year survival rate was worse if tumor size was more than 4 cm vs less than 4 cm.
• 5-year survival rate was similar for various histologic types: 78% for squamous cell carcinomas, 78% for adenocarcinoma, 70% for melanoma, and 73% for other rarer types.
• Multivariate analysis showed increased vaginal cancer mortality rate was associated with:
  • Stage II (HR, 2.35; P < .001) and stage III/IV (HR, 4.67; P < .001) vs stage I
  • Age at diagnosis 70 to 79 years (HR, 1.56; P < .05) and 80 to 89 years (HR, 2.12; P < .001) vs age 50 to 59 years
  • Tumor size more than 4 cm vs less than 4 cm (HR, 1.71; P < .001)
  • Presence vs absence of positive lymph nodes (HR, 2.90; P < .05)
  • Melanoma (HR, 1.51; P < .05) or rarer other type (HR, 1.33; P < .05) vs squamous cell carcinoma
• Vaginal cancer mortality rate was not linked with year of diagnosis, ethnicity, socioeconomic status, grade of tumor, or adenocarcinoma vs squamous cell carcinoma.
• Treatment with surgery or radiation or both was not related to mortality risk, but no treatment vs surgery was linked with increased mortality risk (HR, 2.07; P < .05).
• Analysis of treatment methods stratified by stage showed mortality risk was significantly increased only for no treatment vs surgery in women with stage I or stage III/IV disease.
• Limitations of the study included retrospective design, missing tumor size data in 52% of cases, missing tumor grade data in 33% of cases, no database information on chemotherapy, and no data on potential