Adjunctive and therapeutic progestins in endometrial cancer

With the arrival of progestin therapy for advanced, metastatic and recurrent endometrial cancer a quarter of a century ago, came the discovery that approximately one-third of all these tumors would show a clinical response. Probably no more than half of this group will survive more than 5 years. Identification of the type of patient who is most likely to respond has proven difficult. Both clinical and histopathological characteristics act only as an unreliable guide. The site of metastasis and the time for a recurrence to appear are the most constant of these factors. It is hoped that the steroid receptor content of the tumor will prove to be as valuable as it has been in the case of breast cancer. At the moment this is under investigation with numerous ongoing studies. Type, dosage and mode of administration of progestin do not appear to be critical factors in tumor response, nor does the type of synthetic agent used. However, medroxyprogesterone has been the subject of numerous symposia and is the best researched. It also offers the opportunity of being administered orally and in large doses. All agents are virtually free of toxic effects and cessation on this basis is unusual. For patients with tumors that either do not respond to progestin, or else have a temporary response, other agents--antiestrogens and cytotoxic--may well prove to be of value either simultaneously or sequentially. These possibilities are under current investigation. The definitive therapy of primary 'nonadvanced' disease is not established and is at this point unproven in any significant published randomized study. Orthodox proven methods of treatment, i.e. surgery and irradiation, must form the initial component in every patient's therapy, whatever the stage of the disease. It is hoped that prospective studies will elucidate the place of progestins in an adjunctive primary setting. However, it must be emphasized that such studies must concentrate on 'high-risk' patients. The probability of proof in any group of 'good prognosis' patients--whatever the numbers entered--appears to be very low.