Younger patients with endometrial cancer tend to have disorders such as polycystic ovarian syndrome, chronic anovulation, and infertility, indicative of exposure to intrinsic estrogen excess (17). Lesions in this age group are usually welldifferentiated and of endometrioid subtype with the potential to regress with progestational therapy (18). Althoughstandard treatment for all endometrial cancer is hysterectomy and staging, nonsurgical treatment with hormonal therapy may be an option for appropriately selected women desiring to preserve fertility. Surrogate staging techniques, such as magnetic resonance imaging (MRI), may be employed to evaluate the depth of myometrial invasion or identify extrauterine disease (19,20). The sensitivity of MRI to evaluate these factors is limited and has the potential for underdiagnosis (21).
High regression rates for both endometrial cancer and atypical hyperplasia following treatment with progestin therapy are extensively documented (18,22–28). However, relatively small cohorts of patients and reports of hormone failure suggest caution when counseling patients for conservative management (27,29). In a 2004 meta-analysis, Ramirez et al. reported a comprehensive review of hormonal treatment of grade 1endometrial cancer, including 27 articles with a combined total of 81 patients. A variety of progestational agents were utilized with an overall response rate of 76% (62/81) and the median time to regression was 12 weeks (30). The recurrence rate was 24% among responders; nearly all recurrences occurred within 1year of diagnosis. Only 1month of progestational treatment was required to achieve a response in the 76% of patients without recurrence. Twenty patients achieved pregnancy following treatment. It is important to note that 24% (19/81) of the original cohort never responded to treatment, and only 68% had any documented follow-up endometrial sampling. Progestational therapy can successfully treat disease while preserving fertility for patients with atypical hyperplasia and well-differentiated presumed stage I endometrial cancer. Appropriate patient selection and exclusion criteria remain undefined. Patients must be counseled that failure to identify recurrence or extension of disease during progestational treatment may lead to a delay in definitive surgery and ultimately a compromised prognosis (27).
Continuous progestin therapy with megestrol acetate (40–160 mg per day) is probably the most reliable treatment for reversing complex or atypical hyperplasia. No clear consensus exists for an optimal follow-up interval. Therapy should be continued for at least 2 to 3 months, and endometrial biopsy should be performed 3 to 4 weeks after completion of therapy to assess response.
Periodic endometrial biopsy or transvaginal ultrasonography is advisable in patients being monitored after progestin therapy for atypical hyperplasia because of the presence of undiagnosed cancer in 25% of cases, the 29% progression rate to cancer, and the high recurrence rate after treatment with progestins. In this setting the use of progesterone should be considered a temporary, rather than long-term, treatment. For women with atypical complex hyperplasia who no longer desire fertility, hysterectomy is recommended.
Endometrial Cancer Screening in the General Population
Screening for endometrial cancer should not be undertaken because of the lack of an appropriate, cost-effective, and acceptable test that reduces mortality (31–33). Routine Papanicolaou (Pap) testing is inadequate, and endometrial cytologic assessment is too insensitive and nonspecific to be useful in screening for endometrial cancer, even in a high-risk population. A progesterone challenge test reveals whether the endometrium is primed by estrogen, but it does not identify abnormal endometrial pathology. Transvaginal ultrasonographic examination of the uterus and endometrial biopsy are too expensive to be employed as screening tests.