Endocrine prevention and treatment of prostate cancer

Abstract

The major androgen within the prostate is dihydrotestosterone (DHT). DHT and 5α-reductase are highly associated with prostate cancer. It has been hypothesised that inhibition of 5α-reductase activity might reduce the risk of prostate cancer development, slow tumour progression and even treat the existing disease. The basis for endocrine treatment of prostate cancer is to deprive the cancer cells of androgens. Every type of endocrine treatment carries adverse events which influence quality of life in different ways. 5α-Reductase inhibitors (5-ARI) reduce risk of being diagnosed with prostate cancer but they do not eliminate it. By suppressing PSA from BPH and indolent prostate cancers 5-ARI enhances the ability of a rising PSA to define a group of men at increased risk of clinically significant prostate cancer. Also fewer high-grade cancers are missed because biopsy is more accurate in smaller prostates. Androgen deprivation is an effective treatment for patients with advanced prostate cancer. However, it is not curative, and creates a spectrum of unwanted effects that influence quality of life. Castration remains the frontline treatment for metastatic prostate cancer, where orchiectomy, oestrogen agonists, GnRH agonists and antagonists produce equivalent clinical responses. MAB is not significantly more effective than single agent GnRH agonist or orchiectomy. Nonsteroidal antiandrogen monotherapy is as effective as castration in treatment of locally advanced prostate cancer offering quality of life benefits. Neoadjuvant endocrine treatment has its place mainly in the external beam radiotherapy setting. Increasing data suggest IAD is as effective as continuous ADT. The decision regarding the type of androgen deprivation should be made individually after informing the patient of all available treatment options, including watchful waiting, and on the basis of potential benefits and adverse effects. There are new promising secondary or tertiary forms of endocrine therapies under evaluation, like CTP17A1 inhibitors and more potent antiandrogens including MDV3100, which give new hope for patients developing castration resistant prostate cancer.