March 30, 2017
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Prostate Cancer (cont.)

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Focal therapy

Focal therapy involves ablation of the prostate cancer within the prostate with preservation of the surrounding healthy tissue. A number of focal therapies are being investigated, and a comparison of the efficacy of each of these therapies cannot be made given the limited data on many of these therapies. Focal therapies being investigated include cryotherapy, high-intensity focused ultrasound, laser ablation, photodynamic therapy, irreversible electroporation, radiofrequency ablation, and focal brachytherapy. As many of these are considered experimental, only cryotherapy will be briefly reviewed.

Cryotherapy

Cryotherapy is most frequently used as a salvage treatment after failure of radiation therapy. As an outpatient, hollow needles are placed into the prostate through the perineum (the space between the scrotal sac and the anus) under image guidance. A gas is passed through the needles to freeze the prostate. Warm liquid is passed through the urethra at the same time to protect it. The needles are removed after the procedure. While potentially effective for local control of cancer in the prostate gland, the side effects can be significant and include pain and the inability to urinate. Potential long-term effects include tissue damage in needle-insertion areas, impotence, and incontinence. Cryotherapy is not currently recommend as a primary treatment for management of prostate cancer.

Hormonal therapy

Prostate cancer is highly sensitive to and dependent on the level of the male hormone testosterone, which drives the growth of prostate cancer cells in all but the very high-grade or poorly-differentiated forms of prostate cancer. Testosterone belongs to a family of hormones called androgens, and today front-line hormonal therapy for prostate cancer is called androgen deprivation therapy (ADT).

In the past, this was accomplished by surgical castration called bilateral orchiectomy. In that procedure, the testes were both removed. Today, doctors can block the function of the testes in a controllable and most often reversible fashion with drugs that prevent the production of testosterone (medical castration). These agents can result in shrinkage of the prostate gland, can stop prostate cancer cells from growing for up to several years, and can relieve pain caused by prostate cancer that has spread or metastasized into the bones by shrinking the cancer. The use of ADT does not produce a cure. Over time, the prostate cancer cells will develop an ability to grow despite the lack of hormones (castrate resistance). Another form of hormonal therapy is the use of androgen receptor blockers; these medications prevent testosterone from sticking to the prostate cancer cell and being absorbed into the cell where it can help the cell survive and grow.

Hormonal treatment today is primarily used in the treatment of locally advanced and metastatic prostate cancer. It may be used in conjunction with primary curative therapies (surgical and radiation based) to shrink the cancer/prostate to increase the likelihood of cure of the treatment, neoadjuvant therapy, and with radiation therapy for several years after treatment (adjuvant therapy). However, the primary role of ADT is in the treatment of widespread or metastatic prostate cancer. While it is not a curative treatment in that setting, it can both reduce symptoms and slow down the growth of the prostate cancer to prolong life.

Today medicines used to block testosterone production by the testes include:

  • LH-RH agonists: Leuprolide (Lupron), goserelin (Zoladex), histrelin (Supprelin LA), and triptorelin (Trelstar) are examples of these mediations. These are either given by injection into the muscle or under the skin at varying intervals of at least one month or longer.
  • LH-RH antagonists: Degarelix (Firmagon) is a monthly injection that is given under the skin.

Medications that block the action of testosterone include the androgen receptor blockers

  • Flutamide (Eulexin), bicalutamide (Casodex), nilutamide (Nilandron), and an even more effective form called enzalutamide (Xtandi): Currently Xtandi is recommended for use only in those patients who have metastatic castrate-resistant prostate cancer (prostate cancer that is refractory to traditional ADT).

Both surgical and medical castration result in impotence. They also can cause hot flashes, fatigue, anemia, and thinning of the bones (osteoporosis) over time. These drugs may be given individually or combined with an androgen receptor blocker in what is called a combined androgen blockade.

Other hormonal treatment options include:

  • Estrogen: This female hormone has been utilized in the treatment of prostate cancer. It's mechanism of action remains under study, and its association with a high risk of heart attack and blood clots when used in high doses has diminished the frequency of its use, particularly in front-line therapy. Estrogen and related drugs still play a role in the treatment of metastatic prostate cancer.
  • Adrenal androgen synthesis inhibitors: The adrenal glands, a pair of small glands that are located above the kidneys, also produce a small amount of testosterone. Individuals on traditional ADT have testicular production of testosterone suppressed but still may have testosterone production from the adrenal glands. In individuals on ADT who have continued growth of the prostate cancer (rising PSA), the use of adrenal androgen synthesis inhibitors may be useful. This group includes a drug called ketoconazole, which was primarily developed to treat fungal infections, but has shown to be effective in the treatment of prostate cancer. More recently, an agent called abiraterone acetate (Zytiga) has been developed. It has a similar effect on androgen synthesis, but it is more powerful than an older agent called ketoconazole (Nizoral) and has fewer side effects. The use of Zytiga is considered in individuals failing traditional ADT and individuals who have castrate resistant prostate cancer (failed first line ADT).
  • Steroids: These agents including prednisone may have beneficial hormonal effects in prostate cancer, including slowing the production of androgen by the adrenal glands. They often make the patient feel better, but have many side effects including inducing or worsening diabetes, fluid retention, cataract formation, weight gain, and osteoporosis.
  • Agents that block the conversion of testosterone to its active metabolite: Finasteride (Proscar) and dutasteride (Avodart) have been used in treating prostate cancer by preventing the conversion of testosterone to its active metabolite called DHT (dihydrotestosterone), however, are not currently approved by the Food and Drug Administration (FDA) for this indication. These drugs are frequently utilized for the symptoms of prostate enlargement in men without prostate cancer and appear to reduce the risk of development of prostate cancer. Their side effects are limited. They are used in combination with other agents to optimize androgen blockade. As these medications are not currently approved for use in men with prostate cancer, consult with your physician and insurance provider to ensure that their use is medically appropriate and will be covered.
Medically Reviewed by a Doctor on 11/9/2016

Source: MedicineNet.com
http://www.medicinenet.com/prostate_cancer/article.htm

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