Patient information: Prostate cancer treatment; advanced cancer

PROSTATE CANCER OVERVIEW

Approximately 15 to 20 percent of newly diagnosed prostate cancers are advanced by the time they are detected, meaning that the cancer has spread outside the prostate gland (called locally advanced prostate cancer), involved the lymph nodes or other organs (called metastatic prostate cancer), or both.

This article will discuss the treatment of men with advanced prostate cancer. A separate article discusses the treatment of early stage prostate cancer. (See "Patient information: Prostate cancer treatment; early stage cancer".)

PROSTATE CANCER STAGING

Locally advanced prostate cancer is called stage III cancer while cancer that has spread outside the prostate is called metastatic or stage IV cancer (table 1).

LOCALLY ADVANCED PROSTATE CANCER TREATMENT

Experts are not in complete agreement about the best way to manage locally advanced prostate cancer; treatment options include:

• External beam radiation treatment (EBRT) with or without brachytherapy (see 'Radiation therapy' below.
• Transurethral resection of the prostate (TURP), a type of surgery that can relieve blockage of the bladder caused by the tumor
• Radical prostatectomy, a surgery to remove the entire prostate gland
• Hormone therapy that prevents male hormones from encouraging growth of the prostate cancer cells. This is called androgen deprivation therapy (ADT).

ADT alone is not usually recommended for men with locally advanced prostate cancer. However, it is often used in combination with radiation therapy. Prostatectomy may be a reasonable option for young, otherwise healthy men.

Radiation therapy — There are two forms of radiation therapy used to treat prostate cancer: external beam radiation therapy (EBRT) and brachytherapy (also called interstitial implantation).

External beam radiation therapy — The majority of men with locally advanced prostate cancer are treated with EBRT, usually in conjunction with ADT (see 'ADT plus EBRT' below. EBRT delivers radiation to the area of the prostate and nearby lymph nodes. EBRT is done once per day for approximately eight weeks and most men can continue with normal activities during treatment.

Side effects of EBRT can include needing to rush to the bathroom frequently to urinate, bladder pain, bowel problems, sexual impotence (trouble having an erection), and proctitis (inflammation of the rectum, causing rectal pain or bleeding).

ADT plus EBRT — Most men who have EBRT for locally advanced prostate cancer are also given androgen deprivation therapy (ADT). Having both treatments helps to control the cancer and improves survival. Most experts recommend treatment with ADT for at least two years after the radiation therapy is completed.

Brachytherapy plus EBRT — Brachytherapy is a several hour-long procedure done in the hospital. Brachytherapy is done under anesthesia, and involves placing a radioactive source directly into the prostate gland with ultrasound guidance. There are two types:

• Low-dose-rate (LDR) brachytherapy uses many radioactive seeds or pellets (each about the size of a grain of rice), which are implanted into the prostate. These emit radiation within the gland for a specified period of time and then become inactive. This type of brachytherapy is most commonly used for men with earlier stage disease. This procedure rarely requires an overnight stay in the hospital.
• Men with locally advanced prostate cancer are more likely to be offered high-dose rate (HDR) brachytherapy. This typically requires general anesthesia and an overnight hospital stay. With HDR brachytherapy, a catheter or needle is inserted into the prostate temporarily to deliver radiation to the prostate gland for a period of several hours. HDR brachytherapy is not considered effective in treating locally advanced prostate cancer when used alone; it must be combined with EBRT.

Men who have brachytherapy may have inflammation and swelling of the prostate gland, which can cause difficulty passing urine (urinary retention).

Surgery

Transurethral resection of the prostate — Commonly referred to as a TURP, this surgery removes a part of the prostate gland. This procedure can prevent the prostate tumor from growing for a time, and helps relieve the blockage of urine flow caused by the tumor. However, this provides only a temporary fix, and studies show that TURP is not as effective over the long-term compared to radical prostatectomy.

Radical prostatectomy — Radical prostatectomy is a surgery that completely removes the prostate gland. Although this treatment is often used in men with early prostate cancer, it is not used as often for men with locally advanced prostate cancer. Nonetheless, in selected healthy men with locally advanced prostate cancer, radical prostatectomy may be an option.

Side effects of prostate surgery — Serious or life-threatening complications from prostate surgery are rare. The most common complications are:

• Urinary leakage
• Sexual impotence

Incontinence and impotence are most likely immediately after surgery and tend to improve over time. Age is an important factor in the risk of urinary incontinence after prostatectomy. Older men are more likely to have problems.

The likelihood of impotence after radical prostatectomy also increases with age. A man's previous level of sexual functioning and the use of nerve-sparing surgery also influence this complication. Several treatments can help men who experience impotence after surgery, including sildenafil (Viagra®), vardenafil (Levitra®) and tadalafil (Cialis®). (See "Patient information: Sexual problems in men".)

Androgen deprivation therapy — Androgen deprivation therapy kills the cancer cells and causes the prostate gland to shrink. ADT is usually given in combination with radiation therapy in men with locally advanced prostate cancer. (See 'ADT plus EBRT' above.)

There are several ways in which ADT can be done:

Orchiectomy — ADT can be accomplished by removing the testicles, where most of the male hormone (androgens) are produced; this is called an orchiectomy. The penis and scrotum are not removed.

GnRH agonists — A medicine that prevents the body from making male hormones can be given. These medicines are called GnRH agonists, and include leuprolide (Lupron®) and goserelin (Zoladex®). These are given in a shot every 3 to 6 months.

Combined androgen blockade (CAB) — Sometimes, a medicine called an antiandrogen is given, usually in combination with orchiectomy or a GnRH agonist. Examples include flutamide (Eulexin®) and bicalutamide (Casodex®). Antiandrogens prevent the body from using its own androgens. This combination of treatments is called "combined androgen blockade", or CAB.

Side effects of ADT — Side effects from ADT are related to the lower levels of androgens in a man's body, and include:

• Decreased libido (interest in sex)
• Impotence (trouble having an erection)
• Hot flashes
• Temporary enlargement of the breasts
• A decrease in the size of the penis and/or testicles
• Thinning of hair on the body and head
• Loss of muscle and bone strength, which can lead to osteoporosis (thinning of the bones), and bone fractures

A number of treatments are available to decrease the side effects of ADT. If you cannot tolerate the side effects of ADT, ask your doctor if other treatments are an option. This may include taking a break from treatment, taking antiandrogen treatment alone, or taking one treatment at a time.

SALVAGE TREATMENT FOR A RISING PSA AFTER SURGERY OR RADIATION

Men with advanced prostate cancer and a rising PSA may be curable with further local therapy. Men who have the best chance for cure are those who have less aggressive cancers (ie, lower Gleason grade and lower PSA level), and a slowly rising PSA level.

Salvage radiation — Some men who initially had prostate surgery may be successfully treated with radiation therapy, as long as external beam radiation therapy was not given immediately after surgery.

Salvage brachytherapy — Men who were initially treated with radiation therapy have several treatment options, including salvage prostatectomy, salvage cryotherapy, and salvage brachytherapy. More external beam radiation therapy is not usually recommended due to the high risk of radiation-related side effects. Brachytherapy is described in detail below (see 'Brachytherapy plus EBRT' above.

However, the side effects of salvage brachytherapy can be significant, and may include digestive or urinary complications or the need for a temporary colostomy (to empty the bowels into a bag) or urostomy (to empty the bladder into a bag).

Salvage prostatectomy — Selected men with a rising PSA after radiation therapy for a localized prostate cancer may be able to undergo prostatectomy (termed "salvage" prostatectomy). However, salvage prostatectomy can be associated with serious side effects, and all men are not good candidates.

Cryotherapy — Cryotherapy is sometimes recommended for men who have a rising PSA after external beam radiation therapy.

Androgen deprivation therapy — For men who are not suitable candidates for salvage radiation, brachytherapy, surgery, or cryotherapy, traditional androgen deprivation therapy (ADT) is usually the treatment of choice. ADT is discussed above (see 'Androgen deprivation therapy' above.

METASTATIC (STAGE IV) PROSTATE CANCER TREATMENT

Metastatic prostate cancer is not curable. However, treatment can prolong your life, slow the growth of your cancer, relieve cancer-related symptoms, and improve your quality of life.

Initial androgen deprivation therapy — Androgen deprivation therapy (ADT) is usually recommended first for men with metastatic prostate cancer. This treatment kills the cancer cells and causes the prostate gland to shrink. ADT is described above (see 'Androgen deprivation therapy' above.

Timing of ADT — Many doctors recommend starting treatment when metastatic prostate cancer is diagnosed; the hope is that treatment will slow the growth of the cancer and possibly prolong survival. Others believe that early ADT is not curative and can cause bothersome side effects, and that treatment is best delayed until symptoms of cancer develop. You should discuss the possible benefits and risks of early versus delayed ADT with your doctor.

Duration of benefit of ADT — Most men with advanced prostate cancer initially respond well to ADT, but most have prostate cancer recurrence within two years. At this point, the cancer is termed androgen-resistant, meaning that ADT alone is no longer effective. Once this occurs, secondary hormone therapy is usually considered.

Even when prostate cancer becomes resistant, some form of ADT is usually continued because at least a portion of the cancer cells may still be responsive to removing the influence of androgens (see 'Secondary hormone therapy' below.

Secondary hormone therapy — When advanced prostate cancer becomes androgen-resistant, other hormone treatments may be tried.

• For men taking combined androgen blockade (CAB), the first approach should be to discontinue the antiandrogen (flutamide, nilutamide, bicalutamide).
• Another approach is to try a different type of antiandrogen. Cancer that is resistant to one antiandrogen treatment may not be resistant to another.
• Try another medicine that blocks the activity of androgen in the body, including estrogens, steroids (eg, dexamethasone [Decadron®] or prednisone), or the antifungal medication ketoconazole.

Chemotherapy — Eventually most men with advanced prostate cancer stop responding to all forms of hormone treatment. This situation is referred to as hormone-refractory prostate cancer (HRPC). The next step in treatment is determined by your situation and your preferences, and often includes chemotherapy.

Docetaxel — Most experts consider docetaxel plus prednisone to be the standard chemotherapy regimen for first-line treatment of men with HRPC [1]. Docetaxel is usually given into a vein every three weeks and prednisone is taken by mouth every day.

CLINICAL TRIALS

Progress in treating cancer requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials, or read about clinical trials at:

       www.cancer.gov/clinical_trials/learning/

       www.cancer.gov/clinical_trials/

       http://clinicaltrials.gov/

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Prostate cancer treatment; early stage cancer
Patient information: Sexual problems in men

Professional Level Information:
Cryotherapy for prostate cancer
Management of locally advanced prostate cancer
Management of prostate cancer patients with positive regional lymph nodes
Overview of the clinical presentation, diagnosis, and staging of prostate cancer
Overview of treatment for advanced prostate cancer
Radical prostatectomy for localized prostate cancer
Rising serum PSA after radiation therapy for localized prostate cancer: Salvage local therapy
Rising serum PSA after treatment for localized prostate cancer: Systemic therapy
Rising serum PSA following local therapy for prostate cancer: Definition and risk stratification
Rising serum PSA following local therapy for prostate cancer: Diagnostic evaluation

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• American Society of Clinical Oncology

      (www.cancer.net/portal/site/patient)

• National Comprehensive Cancer Network

      (www.nccn.com)

• National Cancer Institute

       1-800-4-CANCER
       (www.cancer.gov)

• American Cancer Society

       1-800-ACS-2345
      (www.cancer.org)

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• US TOO!

      (www.ustoo.com)

Patient Support — There are a number of online forums where patients can find information and support from other people with similar conditions.

• About.com Cancer Forum

      (http://cancer.about.com/forum)

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