Hormonal therapy of prostate cancer
Prostate cancer is the most common cancer to effect men and the second most common cause of cancer-related death. Premalignant change or prostatic intraepithelial neoplasia has been detected within the prostate glands of men under 30 years of age. The incidence of prostate cancer remains negligible until men reach their 40s from whence it rises steadily and by 80 years 70% of men have detectable tumours at autopsy (1). A majority of prostate cancers arise from the peripheral zone of the prostate and rarely cause obstructive symptoms. Consequently, prostate cancers have historically presented late, with symptoms of metastatic disease. The advent of prostate-specific antigen (PSA) testing has produced a stage shift so that at present over 90% of prostate cancers are diagnosed as organ-confined disease. PSA diagnosis has unmasked a subset of prostate tumours that exhibit an indolent growth pattern and appear destined to remain organ-confined tumours the patient dies with, and not from. US SEER data estimates a 50-year-old man has a 42% chance of developing prostate cancer but only a 3.6% chance of dying from the disease. Features, either clinical or molecular, which would allow clinicians to clearly differentiate indolent from aggressive disease while still at the organ-confined stage, have yet to be identified (1). Adenocarcinoma is the predominant histological subtype of prostate cancer, accounting for 95% of tumours. Prostatic adenocarcinomas arise from androgen receptor-positive epithelial cells. On histological examination, prostate cancers appear multifocal and demonstrate heterogeneity both within individual tumours and across populations. This has created an obstacle as researchers attempt to subclassify prostate cancer and identify the molecular defects responsible for driving prostatic carcinogenesis (1). Of prostate cancers, 80–90% are androgen receptor-positive at diagnosis (2), thus to date the androgen–androgen receptor axis is the sole molecular feature of this disease that has been successfully harnessed as a therapeutic target.