Androgen deprivation therapy and radiation therapy for prostate cancer: the mechanism underlying therapeutic synergy

The first report of modulation of androgens in men with prostate cancer was conducted by Huggins and Hodges in 1941 (1). In a cohort of 8 men with metastatic prostate cancer including osseous metastases, administration of estradiol and/or surgical castration resulted in a durable reduction of alkaline phosphate levels, a marker of osseous disease burden. By surgically eliminating testicular production of testosterone or negatively regulating the hypothalamic-pituitary-gonadal axis through estrogen administration, this was the first demonstration that androgen suppression can induce a measurable biochemical disease response.