Meeting summary: Workshop conference on endocrine therapy of advanced prostate cancer, airlie house, November 3–4, 1996

Investigators from a range of disciplines met at the Airlie House Conference Center in Warrenton, Virginia, on November 3 and 4, 1996, to discuss the biologic principles, prior data, and potential new strategies for use of endocrine therapy in advanced prostate cancer. A general goal of this workshop was to consider whether androgen deprivation of prostate cancer cells may be associated with development of dependence on other hormonal mechanisms for cellular proliferation. The initial session reviewed recent data regarding mutations of the androgen receptor that allow it to initiate transcription in response to estrogens, progestins, and antiandrogens. Evolving concepts of receptor processing and competitive interactions among receptors were presented. The next session addressed the role of estrogens on prostate cellular function and carcinogenesis. Themes included the interaction of androgens with estrogens in mediating differentiated function as well as cell proliferation. The concept that estrogens may mediate the process of carcinogenesis was reviewed. The process of programmed cell death in regulating the rate of tumor growth and the mechanistic role of bcl-2 in androgen ablative therapy were discussed. The following session reviewed data obtained over the past two decades relating to secondary hormonal therapies in prostate cancer. Presentations focused on the use of aromatase inhibitors and antiestrogens, and on withdrawal responses to antiandrogens. The final session considered the difficulties in evaluating objective responses in patients with advanced prostate cancer. A series of endpoints for potential use were identified. A clear consensus emerged that better assessment tools for evaluating pain relief and other quality of life parameters be used for trials of endocrine therapy at this stage of the disease. Side effects and morbidity from experimental therapies should be a major concern in designing new trials. The new biologic data regarding receptor mutations and tumor cell evolution do not provide compelling evidence for initiating large multicenter trials but point to the need for small phase II studies to examine potential efficacy of additional endocrine therapies. Positive results would then lead to larger multicenter trials with incorporation of more highly developed evaluative tools of assessment.