Treatment in the advanced stage

Treatment in the advanced stage

Treatment in the advanced stage

When the diagnosis of prostate cancer is established and the extent and stage of the disease have been determined, the doctor decides together with the patient which options of treatment are used. Here you will find information about different treatment methods in the advanced stage:

  • Wait
  • Hormonal therapy
  • immunotherapy
  • chemotherapy
  • Therapy of bone metastases
  • Supportive and complementary therapy
  • Alternative and experimental therapies
  • checkups
  • Waiting watching

In the metastatic stage, waiting is an option for all patients, regardless of age, concomitant diseases and tumor stage . If one chooses this strategy, the disease is not treated until symptoms occur. As a result, the patient will be spared the side effects of the treatment for as long as possible. Only if there is pain, for example, due to bone metastases does palliative therapy begin, for example with hormones.

Hormonal therapy

Who receives hormone therapy?

In the palliative situation, hormonal treatment is the standard by which tumor growth can be stopped for some time – often for years.

One can begin a hormone therapy immediately in the diagnosis of advanced prostate cancer. If, however, the tumor still does not cause any discomfort, it is not certain whether the advantages of hormonal therapy are the disadvantages to be expected, ie side effects. Since an immediately started therapy does not have any advantages in terms of the survival time of a delayed start, it is possible to wait until the first symptoms occur.

Conventional hormone therapy, as practiced for many years, results in the improvement of symptoms (eg, pain relief), reduction in tumor size and / or decrease in PSA in most patients. However, the effect is not permanent and over time develops a resistance to the withdrawal of androgens. In this so-called “cathastization-resistant” stage, chemotherapy has previously been the only patient, but new hormonal therapies with fewer side effects have been available recently.

How does hormone therapy work?

Prostate cells have special binding sites, the androgen receptors, to which testosterone attaches. This initiates a signal which is transported through various biochemical processes in the cell nucleus, where the cell division and cell growth is then carried out. This mechanism is disrupted in prostate carcinoma cells, leading to uncontrolled growth.

About 90-95% of the androgens are produced in the testes, the remaining 5-10% in the adrenal cortex. Hormones formed in the hypothalamus in the brain, especially the luteinizing hormone releasing hormone (LHRH), control androgen formation.

All these connections and mechanisms are the starting points for different types of hormonal treatment of prostate cancer. Basically two approaches to endocrine therapy can be distinguished:

  • The formation of androgens is suppressed.
  • The effect of androgens on the tumor cells is inhibited.

Side effects of hormone therapy

Since hormones over complicated relationships control many different processes in the body, hormone therapy can have a wide range of effects.

Typical side effects of castration, ie, hormone deprivation, are heat buildup and a breakdown of bone density with the risk of osteoporosis and bone fractures. Sexual interest (libido) can go back and decrease the potency. Men under hormone withdrawal therapy tend to be weight gain and muscle reduction and also the mental performance (“cognitive ability”) can be adversely affected. Long-term hormone therapy also increases the risk of fat metabolism disorders, diabetes, and consequently cardiovascular disease.

What are the hormonal therapies?

Approach 1: suppression of hormone production in the testes (castration)

The elimination of hormone production can be achieved in two ways: by means of surgical removal of the hormone-producing tissue, ie of the testes , or by administration of drugs.

The orchiectomy , ie the removal of the testes, is one of the oldest methods for the treatment of prostate cancer. Its advantage is that it is a one-off measure. However, it can not be reversed and associated with side effects such as heat buildup, libido, impotence, and osteoporosis. Since there are equally effective drug castration forms, the orchiectomy is rarely performed today.

In the drug suppression of testosterone formation, two active ingredient groups are distinguished:

The specificity of the LHRH analogues at the beginning of the treatment is to first cause a testosterone thrust. In order to block the effect of the testosterone, the combination with so-called antiandrogens is required in the first weeks (see androgen blockade). The combination of LHRH analogue and antiandrogen is called maximum androgen blockade (MAB).

Suppression of hormone production with LHRH analogues : The LHRH analogues (also called GnRH agonists, eg Buserelin, Goserelin, Leuprorelin, Triptorelin) intervene in the hormone control loop and thus stop the production of testosterone in the testes. Since LHRH analogues initially cause a hormonal thrust, they are combined with androgen receptor blockers at the beginning of the therapy for a few weeks.

Suppression of testosterone production with LHRH antagonists : LHRH antagonists (also known as GnRH antagonists, eg Abarelix, degarelix) also intervene in the hormone control loop, so that no testosterone is produced in the testes. In contrast to the LHRH analogues, however, an immediate suppression of hormone production without hormone thrust occurs.

Both LHRH analogs and LHRH antagonists are administered as a syringe, which the patient receives monthly or all, 2, 3, 6 or 12 months depending on the preparation.

In the case of drug castration, it is a permanent therapy, which is continued as long as it shows an effect. There is, however, also the approach of so-called intermittent therapy , in which multi-month treatment phases alternate with therapid-free intervals. The background is that in the non-treatment phases, the side effects of the hormone withdrawal part go back, which can be associated with a return of the potency and an improvement in the quality of life. However, it is not entirely certain whether intermittent therapy is as effective as long-term therapy. While some studies have shown equivalency, intermittent therapy patients died slightly more frequently in other studies.

Approach 2: androgen receptor blockade on the tumor cell

Androgen receptor blockers (also called antiandrogens, eg bicalutamide, flutamide, nilutamide) suppress the effect of testosterone by blocking the androgen receptor in the tumor cell. Under certain circumstances, they can be used in addition to LHRH analogues (“maximum androgen blockade”) to completely shield the cancer from growth-stimulating hormones that are still present in small amounts despite the therapy. However, this combination therapy is associated with increased side effects.

On the whole, ie, as an alternative to drug castration, androgen receptor blockers are generally less frequently used due to their slightly lower efficacy. However, since the testosterone level is not affected, the typical side effects of hormone drainage remain as heat buildup and potency problems.

A typical side-effect of androgen receptor blockers is the painful swelling of the mammary glands (gynecomastia).

Approach 3: suppression of testosterone production also outside the testes

In the course of hormone therapy, the tumor cells develop various mechanisms to circumvent the androgen deficiency, which is called castration resistance . Smallest amounts of testosterone can now be sufficient to allow the tumor to grow further.

A hormonal therapy with the active substance Abirateron intervenes in the hormone control circuit and thus prevents the production of testosterone not only in the testes, but also in the adrenal and the tumor tissue itself. Therefore Abiraterone can still work in case of castration-resistant prostate carcinoma.

Abiraterone has been available in tablet form since 2012 and is currently recommended for the therapy of castration-resistant prostate cancer, as long as the patients still have no symptoms or mild symptoms (eg pain due to bone metastases). Abiraterone can also be used after an initial chemotherapy. During the Abirateron therapy, the original hormone therapy, For example, with LHRH analogs.

Typical side effects of Abiraterone are water retention, potassium deficiency and hypertension. In order to reduce these effects caused by the mechanism of action, prednisone or prednisolone are additionally taken during the abiraterone therapy.

Approach 4: androgen receptor signaling pathway blockers

The androgen receptor pathway blocker enzalutamide not only prevents the binding of testosterone to the androgen receptor, but also blocks signal propagation inside the cell. This hormonal therapy has been available since 2013 and has so far only been used in patients with castration-resistant prostate carcinoma, which do not have strong symptoms and therefore do not require chemotherapy. Even during the enzalutamide treatment, the hormone withdrawal therapy is continued in parallel with LHRH analogues.

The most common side effects with enzalutamide are fatigue, hot flashes and headaches; And the side effects of hormone withdrawal therapy.

immunotherapy

The drug Sipuleucel-T is a type of vaccine that triggers an immune reaction directed against the prostate carcinoma cells of the body. For this purpose, certain blood cells (T cells) are first removed from the patient and modified in such a way that they can “recognize” the prostate carcinoma cells. After the altered cells have been re-transplanted to the patient, they can target the tumor cells.

The side effects of the therapy – especially chills and fever – are typical for body-borne immune reactions.

The immunotherapy with Sipuleucel-T has been available in Europe since 2013. It can be used in the case of a catastation-resistant disease stage if there are still no or slight symptoms and no metastases are present in soft tissues (lung, liver). In daily practice, this therapy is rarely used because of the high logistical effort and the enormous costs.

chemotherapy

In chemotherapy , drugs are used, so-called cytostatics , which inhibit the growth of cancer cells and thereby destroy them. The cytotoxic agents are generally administered as infusion, spread throughout the entire body and thus also reach tumor cells that have already spread to other body regions.

Chemotherapy is associated with more severe side effects than hormonal therapies. Therefore, it is usually used only when all hormonal options are exhausted and / or if a fast and effective therapy is necessary. The latter is the case, above all, with strong symptoms, Eg in case of violent bone pain or if a cross-section paralysis is threatened by spinal metastases. Chemotherapies are also used in the case of an acute risk of life, for example due to liver or lung metastases.

The currently preferred chemotherapeutic agent in prostate cancer is docetaxel , a cytostatic agent from the taxane group. Cabazitaxel is also a taxane and is used in patients who are already pre-treated with docetaxel.

What are the consequences of chemotherapy?

Chemotherapy affects all rapidly dividing lines. Unfortunately, this includes not only the malignant cancer cells, but also healthy cells such as mucous membranes of the digestive tract, hair root cells and blood-forming cells of the bone marrow. The most common side effects of chemotherapy are therefore nausea and vomiting, diarrhea and hair loss, allergic reactions and increased susceptibility to infections. However, these undesirable side effects can now be estimated well and mitigated by corresponding measures. They usually disappear after the end of the chemotherapy.

Treatment of bone metastases

Advanced prostate carcinomas often form daughter tumors (metastases) in the bones. These can cause severe pain. In addition, they damage the bone, so that bone fractures are easy.

There are a number of ways to treat bone metastases specifically and to alleviate the pain. This includes, on the one hand, the targeted irradiation of individual metastases. Radiological remedies , such as radium-223, samarium-153, strontium-89, can also be achieved by the administration of certain radioactive substances that accumulate in diseased bones and irradiate them from the inside. Certain antibodies (denosumab) can delay the onset of symptoms due to bone metastases. In addition, treatment with other drugs that inhibit bone degradation ( bisphosphonates , eg zoledronic acid) may reduce the risk of bone metastasis complications and relieve pain.

Supportive and complementary therapy

The treatment of cancer is only effective and meaningful if at the same time so-called supportive measures are used prophylactically and therapeutically. Treatment of treatment-related side effects such as nausea and vomiting, pain therapy for painful or painful pain, nutritional changes and help with psychological and social problems are an important addition to the direct treatment of tumor disease. Supportive therapy also includes targeted treatment of individual patients metastases.

The extra – not alternative! – Treatment with herbal supplements can effectively support cancer therapy and relieve side effects. It is important to consult with the treating physician the sensible use of such complementary therapies, since naturopathic preparations can also mitigate the effects of antihormone, chemo or target-oriented therapy or strengthen their side effects.

pain treatment

In the advanced stage of a prostate disease, the patient often experiences pain. They affect their quality of life more strongly than the tumor itself. One of the most important measures is now the effective pain control . With the drugs and methods available today, tumor pain can be alleviated in most cases. Depending on the degree of severity, different groups of medicines are used, and in the case of very severe pain, morphine. They are generally taken in the form of tablets, some are also available as pavement.

Important: The pain does not have to be borne! And, you do not have to wait for the pain to take painkillers, but the tumor pain is treated before it occurs. For this, the intake rhythm is set so that there is always enough active substance in the body so that no pain occurs.

Alternative and experimental therapies

Patients today find an immense range of experimental and alternative methods. Whether mistletoe or thymus preparations, whether self-healing or self-healing, whether homeopathy or extreme diets: Evaluating whether it is effective therapies or charlatanics is not always easy. Often, the rejection of school medicine therapies and the herpodulation with “gentler”, “alternative” methods lose important time, so that an initially curable cancer is metastasized and thus becomes the incurable disease. However, there are always new treatment approaches which are not yet established and are still in the experimental stage (eg hyperthermia ), which in the future could become quite significant. Again, the treating physician should be informed before starting any alternative or experimental therapy. It can relate the usefulness of the methods to possible risks and not least to the often high costs.

checkups

In the case of advanced prostate cancer, regular follow-up examinations are primarily used to detect or avoid complications, For example by bone metastases or by pressure of the tumor on surrounding organs and tissues. In addition to a general physical examination, a digital-rectal examination and the examination of the PSA value, various disease-specific blood values ​​(testosterone, tumor markers) can also be determined. Imaging methods, For example, the bone scintigraphy, are used only in cases of specific suspicion of a progress of the disease.

An important task of the regular investigations is also to monitor and possibly treat possible long-term and / or late effects of the treatment, for example osteoporosis, liver damage, changes of the blood values, diabetes or cardiac diseases.

The intervals of the control tests depend on the stage of the disease.

  • In patients without metastases, investigations at intervals of 3-6 months are sufficient.
  • In patients with metastases whose PSA is below 4 ng / ml, whose general condition is good and which have no or only mild symptoms (eg pain), follow-up checks every 6 months.
  • The control intervals are determined individually for patients in the case of castration resistant.

In case of complaints, the next check-up date should not be waited for, but the doctor should be called immediately.