Androgen deprivation therapy (ADT), also called androgen ablation therapy or androgen suppression therapy, is an antihormone therapy whose main use is in treating prostate cancer. Prostate cancer cells usually require androgen hormones, such as testosterone, to grow. ADT reduces the levels of androgen hormones, with drugs or surgery, to prevent the prostate cancer cells from growing. The pharmaceutical approaches include antiandrogens and chemical castration.
Several studies have concluded that ADT has demonstrated benefit in patients with metastatic disease, and as an adjunct to radiation therapy in patients with locally advanced disease, as well as those with unfavorable intermediate-risk or high-risk localized disease. However, in patients with low-risk prostate cancer, ADT has demonstrated no survival advantage, and significant harm, such as impotence, diabetes and bone loss.
The therapy can also eliminate cancer cells by inducing androgen deprivation-induced senescence. Lowering androgen levels or stopping them from getting into prostate cancer cells often makes prostate cancer shrink or grow more slowly for a time. However, this treatment needs to be combined with radiation therapy (RT) because ADT itself does not eradicate the cancer; it just decreases its aggressiveness.
Types
Method based on surgery
Orchiectomy (surgical castration) It consists of removing the testicles, the organ where androgens are synthesized, of the cancer patient. It is the most radical treatment for ending the production of androgens. Moreover it is the easiest and least expensive one. The main disadvantage is that surgical castration is a permanent method.
Methods based on drugs
Chemical castration
The synthesis of testosterone is mediated by a chain of processes that start in the brain. When the body detects a low level of testosterone, the hypothalamus starts to produce LHRH. LHRH activates the synthesis of LH (Luteinizing hormone) within the pituitary gland. LH induces testosterone synthesis within the testicles. There are two different medicines, LHRH agonists and antagonists, which both lower the amount of testosterone made by the testicles. They work by inhibiting the formation of LH in the pituitary gland. The LHRH agonists produce a sudden increase on levels of testosterone followed by a huge falling, process called flare, whereas LHRH antagonists decrease directly the amount of testosterone. LHRH agonists and antagonists used in androgen deprivation therapy include leuprorelin (leuprolide), goserelin, triptorelin, histrelin, buserelin, and degarelix. These drugs are injected under the skin achieving the same result as surgical castration. Chemical castration may be preferred to surgical castration as it keeps the testes intact. Antiandrogen therapy
Adrenal glands were discovered as another center of androgen production even after a castration process. Therefore a complementary treatment was developed that uses antiandrogens to block the body's ability to use any androgens. Prostate cells contain an Androgen Receptor (AR), that when stimulated by androgens like testosterone, promotes growth and maintains prostatic differentiation. These pro-growth signals, however, can be problematic when they occur in a cancer cell. Antiandrogens can enter cells and prevent the binding of testosterone to the receptor proteins, due to their higher affinity for the Androgen Receptor. The main antiandrogens are cyproterone acetate, flutamide, nilutamide, bicalutamide, and enzalutamide which are all administered in oral pill form.
New antiandrogens that target testosterone synthesis (abiraterone acetate and seviteronel) or AR nuclear translocation (enzalutamide, apalutamide, and darolutamide), as well as combined therapies (galeterone) have been recently developed and may function to better target androgen-responsive cells in combination with ADT. But these too may have negative adverse roles in the development of CRPC.