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Testosterone, the male sex hormone, controls the development and activity of the healthy prostate. Due to changes in hormone distribution, fluctuations and imbalances in the male hormone balance occur with age. The result is growth of benign but also stimulation of malignant prostate cells.
Prostate cancer cells normally require male sex hormones (androgens), especially testosterone, to grow.
This realization results in one of the most important pillars of prostate cancer drug therapy:
Suppression of testosterone action on the prostate, leads to slowing of prostate (cancer) cell growth and, in some cases, cell death (apoptosis).
The aim of hormone therapy is therefore to deprive the tumor of these androgens. GnRH agonists or so-called anti-androgens are used. While GnRH agonists inhibit the production of testosterone in the testes, anti-androgens block the effect of the hormones on the tumor cells.
Even if no cure can be achieved with hormone therapy, tumor growth can be delayed for some time - often for years - and symptoms alleviated in 80 percent of patients.
Whether and for how long hormone therapy is sought depends on both the tumor stage, the type of therapy, the size of the prostate, and the patient's age, general condition, and expected life expectancy. Hormone therapy is generally considered for:
Patients with localized high-risk prostate cancer.
In high-risk patients (PSA>20ng/ml, Gleason score >6, sedimentation margin not tumor-free after surgery, lymph nodes affected), hormone therapy is recommended over a period of time to minimize the risk of recurrence. The administration of hormones in combination with external radiation or brachytherapy may also be useful.
Patientswith tumor recurrence
If a relapse occurs after radiotherapy or surgery, hormone therapy or a combination of hormone therapy and radiotherapy is the treatment of choice for many patients.
Patients with metastatic prostate cancer
In patients with advanced prostate cancer that has already formed numerous metastases in the bones or other organs, hormone therapy is usually used as a permanent treatment. Local treatment alone (surgery, radiation, brachytherapy) cannot lead to cure in such cases.
Elderly patients with local tumor
If surgery is too risky and radiation is not possible or not desired because of the side effects, hormone treatment can be considered. However, a long-term cure cannot be achieved.
GnRH agonists inhibit testosterone production in the testes. Possible side effects of the hormone change include hot flashes, sweating, and a decrease in potency and performance. If the hormone treatment is limited in time, however, testosterone levels can recover after the medication is discontinued.
Anti-androgens suppress the effect of testosterone by blocking its uptake into the cancer cell. There are two different classes of substances here with comparable effects: the steroidal anti-androgens and the non-steroidal anti-androgens. The latter have the advantage that they can preserve general performance, bone density and even potency. Anti-androgens are also administered at the beginning of hormone treatment, usually concomitantly with GnRH agonists, for a few days to compensate for fluctuations in hormone balance.
The effect of conventional hormone treatment is usually not permanent and the tumor cells become resistant to hormone deprivation after some time. This is then referred to as "castration-resistant" prostate carcinoma. While chemotherapy used to be used in such cases to inhibit tumor growth, new hormonally active substances with different mechanisms of action are now available. Which preparations are used depends on several factors and is carefully assessed together with the physician.
Abiraterone
Abiraterone (Zytiga®) inhibits hormone production not only in the testis, but also in the adrenal glands and in the tumor itself. The progression of the disease is slowed and tumor-related symptoms are alleviated. Abiraterone is administered once daily in tablet form together with a small dose of cortisone. Possible side effects may include increased blood pressure or diarrhea. In general, however, the drug is well tolerated.
The drug is used in patients with castration-resistant prostate cancer who already have metastases in other organs, whether or not chemotherapy has already been administered.
Enzalutamide
Enzalutamide (Xtandi®) blocks the binding sites of the male sex hormones and thus prevents testosterone from entering the tumor cell. This slows tumor growth and slows the formation of further metastases. The most common side effects are chronic fatigue and gastrointestinal problems.
The drug is used in patients with castration-resistant prostate cancer who already have metastases in other organs, whether or not chemotherapy has already been administered.
Apalutamide
Apalutamide (Erleada®) is a new generation non-steroidal antiandrogen. It inhibits the androgen receptor and thus blocks the penetration of testosterone into the tumor cell. The substance thus has the same pharmacological mode of action as enzalutamide. While fatigue occurs more frequently under enzalutamide, skin rashes occur more frequently under apalutamide.
Apalutamide is used for the treatment of non-metastatic castration-resistant prostate cancer. The drug is indicated in patients at high risk of developing metastases(PSA doubling time ≤ 10 months). Since January 2020, the approval has been extended to patientswith metastatic hormone-sensitive prostate cancer.
