What are the differences between hormonal treatment and chemotherapy?

Hormonal therapy is the mainstay of treatment for symptomatic, advanced-staged prostate cancer. A vast majority of prostate cancers, particularly initially, are dependent on testosterone (the male hormone produced by the testes) for their growth and spread. The objective of hormonal treatment is to withdraw this source of sustenance for prostate cancer cells in an attempt to slow down or control this disease. The following are treatments available for hormonal therapy:

Orchiectomy is the surgical removal of the testicles. Luteinizing hormone-releasing hormone (LHRH) agonists, such as leuprolide (Lupron, Viadur, Eligard), goserelin (Zoladex), or buserelin (Suprefact), stop the production of testosterone from the testes and induce a state of "medical castration" (castration without surgery). Many men prefer this over surgical castration.

Antiandrogens, such as flutamide (Eulexin) or bicalutamide (Casodex), block the action of testosterone on the prostate cancer cells and other parts of the body. Each of the above two classes of medicines produce symptomatic relief in about 80% of patients. Improvement is often dramatic.

Side effects of these medications vary. Orchiectomy and LHRH agonists may cause impotence, hot flashes, and loss of sexual desire. Antiandrogens may cause nausea, vomiting, diarrhea, and breast enlargement or tenderness. Any of these therapies can weaken bones and lead to osteoporosis and bone fracture.

Other agents that are helpful include the following: progestins such as megestrol acetate given daily orally and other drugs that inhibit androgen production such as aminoglutethimide (Cytadren) or ketoconazole (Nizoral, Extina, Xolegel, Kuric). These agents are effective but are sometimes difficult to tolerate. Corticosteroids are often given simultaneously.

As opposed to hormonal therapy, chemotherapy provides relief in only 20%-25% of symptomatic patients with prostate cancer. Various regimens are being used. Estramustine, cisplatin, 5-FU, vinorelbine, and mitoxantrone are the most popular agents. However, recently docetaxel (Taxotere) has become the drug of choice used by oncologists in treating castrate-resistant prostate cancer (prostate cancer which has become unresponsive to hormonal therapy).

When to use hormonal therapy and chemotherapy depends on the nature of the prostate cancer itself. If the prostate cancer is hormone-sensitive, then hormonal therapy is the therapy of choice. When the cancer becomes hormone-resistant (for example, manipulation of the hormone levels has no effect on the prostate cancer), then the only potential therapy available to the patient is chemotherapy. Chemotherapy, then, is used generally when advanced prostate cancer is hormone-resistant. Unfortunately, chemotherapy after hormone therapy is nowhere near as effective as hormonal therapy because the cancer itself has often evolved to become more aggressive so that the prognosis is significantly worse. When prostate cancer transforms from being hormone-sensitive to hormone-resistant, the prognosis has taken a significant turn for the worse and the chemotherapy option at that particular time is usually the only treatment option available.

Other factors considered in choosing treatment include the age, general health, and preference of the individual and the Gleason score and stage of the cancer. The results of the PSA test sometimes also can help to decide on the treatment. For example, a borderline elevation of the PSA (4-10), if shown to be due to a prostate cancer, suggests that the cancer is confined to the gland. If other tests also point to an organ-confined tumor, surgery or possibly radiation can be considered to attempt a cure. In contrast, a very high PSA (for example, over 30 or 40) raises the possibility of metastases. If the metastases are then confirmed by other tests, the treatment options would be limited to hormonal therapy or chemotherapy.

PSA tests also should be done periodically after treatment to help assess the results of treatment. For example, an increasing PSA suggests growth or spread of the cancer, despite the treatment. In contrast, a decreasing PSA indicates improvement. As a matter of fact, a post-treatment undetectable PSA (PSA less than 0.05 or 0.1 ng/ml) may indicate complete control or cure of the cancer.

What is chemotherapy for prostate cancer?

Chemotherapeutic agents, or chemotherapy, are anticancer drugs. They are used (for hormone resistant prostate cancer) as a palliative treatment (palliation to relieve symptoms) in patients with advanced cancer for whom a cure is unattainable. Recall that the goal of palliation is simply to slow the tumor's growth and relieve the patient's symptoms. Chemotherapy is not ordinarily used for organ-confined or locally advanced prostate cancers because a cure in these cases is possible with other treatments. Currently, chemotherapy is used only for advanced metastatic prostate cancers that have failed to respond to other treatments.

Several chemotherapeutic agents have been used effectively to palliate metastatic prostate cancer. One such agent is estramustine (Emcyt). Another agent called mitoxantrone (Novantrone) has been shown to be effective in combination with prednisone for palliating androgen-independent prostate cancer. As mentioned previously, metastatic tumors that have not responded specifically to hormonal therapy are referred to as castrate-resistant prostate cancers. Newer chemotherapy medicines like docetaxel (Taxotere) have shown some promise in prolonging the survival of some patients with extensive prostate cancer. They may also decrease the pain related to widespread cancer. However, this comes at the cost of significant side effects that may impact quality of life.

The more common side effects of chemotherapy include weakness, nausea, hair loss, and suppression of the bone marrow. The suppression of marrow, in turn, can decrease the red blood cells (causing anemia), the white blood cells (leading to infections), and the platelets (resulting in bleeding).

What is HIFU for prostate cancer?

HIFU, which stands for high intensity focused ultrasound, was first developed as a treatment of benign prostatic hyperplasia (BPH) and now is also being used as a procedure for the killing of prostate cancer cells. This procedure utilizes transrectal (across the rectum) ultrasound that is highly focused into a small area, creating intense heat of 80-100 C, which is lethal to prostate cancer tissue. However, the published clinical experience with HIFU for this application is limited and the procedure is not yet approved by the FDA for use in the United States.

What is cryotherapy for prostate cancer?

Cryotherapy is one of the newer treatments that is being evaluated for use in the early stage of prostate cancer. This treatment kills the cancer cells by freezing them. The freezing is accomplished by inserting a freezing liquid (for example, liquid nitrogen or argon) through needles directly into the prostate gland. The procedure is accomplished under the guidance of ultrasound images. Actually, cryotherapy is not a new technique. Rather, it is a modification of a procedure that was tried previously but had an unacceptably high rate of complications. Thus, cryotherapy was used in the 1960s to freeze the lining of the stomach to treat ulcers but was discontinued because it also severely damaged the lining of the stomach.

At present, cryotherapy is recommended for patients with locally advanced prostate cancer who, for whatever reason, are not candidates for the more established treatments. Cryotherapy is further being studied to determine which other patients might benefit from this treatment. For example, studies are under way to establish whether cryotherapy is beneficial as an initial treatment for organ-confined (localized) prostate cancer. The effectiveness of cryotherapy in eliminating prostate cancer, however, has not yet been proven. We do know that sometimes the freezing liquid fails to kill all of the cancer cells. Moreover, the potential side effects of this treatment include damage to the urethra and bladder. This damage can cause obstruction (blockage) of the urethra, fistulas (abnormal tunnels) that leak urine, or serious infections.

What about hormonal treatment for prostate cancer?

The male (androgenic) hormone is called testosterone. It stimulates the growth of cancerous prostatic cells and, therefore, is the primary fuel for the growth of prostate cancer. The idea of all of the hormonal treatments (medical and surgical), in short, is to decrease the stimulation by testosterone of the cancerous prostatic cells. Testosterone normally is produced by the testes in response to stimulation from a hormonal signal called LH-RH. The LH-RH stands for luteinizing hormone-releasing hormone and is also called gonadotropin-releasing hormone. This hormone comes from a control station in the brain and travels in the bloodstream to the testes. Once there, the LH-RH stimulates the testes to produce and release testosterone.

Hormonal treatment, also referred to as androgen deprivation (depriving the prostate of testosterone), can be accomplished surgically or medically. The surgical hormonal treatment is removal of the testes in an operation called an orchiectomy or a castration. This surgery thus removes the body's source of testosterone. The medical hormonal treatment involves taking one or two types of medication. One type is referred to as the LH-RH agonists. They work by competing with the body's own LH-RH. These drugs thereby inhibit (block) the release of LH-RH from the brain. The other type of drug is referred to as anti-androgenic, meaning that these drugs work against the male hormone. That is, they work by blocking the effect of testosterone itself on the prostate.

Today, most men electing hormonal treatment choose medication over surgery, probably because they view surgical castration as more devastating cosmetically or psychologically. Actually, however, the effectiveness and side effects of medical hormonal treatment as compared to surgical hormonal treatment are very much the same. Both types of hormonal treatment usually effectively eliminate stimulation of the cancer cells by testosterone. Some tumors of the prostate, however, do not respond to this form of treatment. They are referred to as androgen-independent prostate cancers. The principal side effects of all of these hormonal treatments (that is, the side effects of androgenic deprivation) are enlarged breasts (gynecomastia) that often are tender, flushing (like hot flashes), and impotence.

The LH-RH agonists, leuprolide (Lupron) or goserelin (Zoladex), are given as monthly injections in the doctor's office. The anti-androgenic drugs, flutamide (Eulexin) or bicalutamide (Casodex), are oral capsules that are used usually in combination with the LH-RH agonists. The LH-RH agonists are often effective alone. The anti-androgenic drugs are added, however, if the cancer progresses despite the use of the LH-RH agonists. The hormonal treatments may have value, as well, when combined with radiation therapy. Current evidence suggests that hormonal therapy enhances the therapeutic effect of radiation.

Generally, hormonal treatment is reserved for individuals who have advanced prostate cancer with local spread or metastases. Occasionally, an individual with organ-confined (localized) prostate cancer will receive hormonal treatment because he has severe associated medical problems or simply because he refuses to undergo surgery or radiation. Hormonal treatment is used in less than 10% of men with organ-confined (localized) prostate cancer. Remember that the intent of hormonal therapy usually is palliative. This means that the goal is to control the cancer rather than cure it because a cure is not possible.

What about radiation therapy for prostate cancer?

The goal of radiotherapy is to damage the cancer cells and stop their growth or kill them. This works because the rapidly dividing (reproducing) cancer cells are more vulnerable to destruction by the radiation than are the neighboring normal cells. Clinical trials have been conducted using radiation therapy for patients with organ-confined (localized) prostate cancer. These trials have shown that radiation therapy resulted in a rate of survival (being alive) at 10 years after treatment that is comparable to that for radical prostatectomy. Incontinence and impotence can occur as complications of radiation therapy, as with surgery, although perhaps less often than with surgery. More data are needed, however, on the risks and benefits of radiation therapy beyond 10 years, especially because late recurrences (reappearances) of the cancer can sometimes occur after radiation.

Choosing between radiation and surgery to treat organ-confined prostate cancer involves considerations of the patient's preference, age, and coexisting medical conditions (fitness for surgery), as well as of the extent of the cancer. Approximately 30% of patients with organ-confined prostate cancer are treated with radiation. Sometimes, oncologists combine radiation therapy with surgery or hormonal therapy in an effort to improve the long-term results of treatment in the early or later stages of prostate cancer.

Radiation therapy can be given either as external beam radiation over perhaps six or seven weeks or as an implant of radioactive seeds (brachytherapy) directly into the prostate. In external beam radiation, high energy X-rays are aimed at the tumor and the area immediately surrounding it. In brachytherapy, radioactive seeds are inserted through needles into the prostate gland under the guidance of transrectally taken ultrasound pictures. Brachy, from the Greek language, means short. The term brachytherapy thus refers to placing the treatment (radiation therapy) directly into or a short distance away from the cancerous target tissue. The theoretical advantage of brachytherapy over external beam radiation is that delivering the radiation energy directly into the prostate tissue should minimize damage to the surrounding tissues and organs.

Potential disadvantages of radiation therapy include a transient swelling of the prostate that may cause obstruction to the flow of urine and increase symptoms that may already be present because of an enlarged prostate. Side effects of external beam radiation include skin burning or irritation and hair loss at the area where the radiation beam goes through the skin. Both can cause severe fatigue, diarrhea, and discomfort on urination. These effects are almost always temporary. However, there are concerns about the long-term effects of radiation, and although still not proven, some studies have reported a higher chance of developing bladder or rectal cancer many years after undergoing radiation for prostate cancer. Although surgery can be done in case radiation therapy fails to cure prostate cancer (salvage radical prostatectomy), it is fraught with greater surgical difficulty and involves a significantly higher chances of complications like impotence and urinary incontinence.

What about prostate cancer surgery?

The surgical treatment for prostate cancer is commonly referred to as a radical prostatectomy, which is the removal of the entire prostate gland. The entire prostate, seminal vesicles, and ampulla of the vas deferens are removed, and the bladder is connected to the membranous urethra to allow free urination.

The radical prostatectomy is the most common treatment for organ confined or localized prostate cancer in the United States. This operation is currently performed in about 36% of patients with organ-confined (localized) prostate cancer. The American Cancer Society estimates a 90% cure rate nationwide when the disease is confined to the prostate and the entire gland is removed. The potential complications of a radical prostatectomy include the risks of anesthesia, local bleeding, impotence (loss of sexual function) in 30%-70% of patients, and incontinence (loss of control of urination) in 3%-10% of patients.

Great strides have been made in lowering the frequency of the complications of radical prostatectomy. These advances have been accomplished largely through improved anesthesia and surgical techniques. The improved surgical techniques, in turn, stem from a better understanding of the key anatomy and physiology of sexual potency and urinary continence. Specifically, the recent introduction of nerve-sparing techniques for the prostatectomy has helped to reduce the frequency of impotence and incontinence. Of men who undergo these newer techniques, 98% are continent, and 60% are able to have an erection.

Radical prostatectomy can be performed by open surgery, laparoscopic surgery, or by robotic surgery (robotic assisted radical prostatectomy). Currently, almost 70% of radical prostatectomy surgeries in the U.S. are performed using the of the Da Vinci robotic system. For robot-assisted surgery, five small incisions are made in the abdomen through which the surgeon inserts tube-like instruments, including a small camera. This creates a magnified three-dimensional view of the surgical area. The instruments are attached to a mechanical device, and the surgeon sits at a console and guides the instruments through a viewing device to perform the surgery. The instrument tips can be moved in a variety of ways under the control of the surgeon to achieve greater precision in surgery. So far, studies show that traditional open prostatectomy and robotic prostatectomy have had similar outcomes related to cancer-free survival rates, urinary continence, and sexual function. However, in terms of blood loss during surgery and pain and recovery after the procedure, robotic surgery has been shown to have a significant advantage.

If post-treatment impotence does occur, it can be treated by sildenafil (Viagra) tablets, injections of such medications as alprostadil (Caverject) into the penis, various devices to pump up or stiffen the penis, or a penile prosthesis (an artificial penis). Incontinence after treatment often improves with time, special exercises, and medications to improve the control of urination. Occasionally, however, incontinence requires implanting an artificial sphincter around the urethra. The artificial sphincter is made up of muscle or other material and is designed to control the flow of urine through the urethra. 

Transurethral resection of the prostate (TURP) involves the removal of a part of the prostate by an instrument inserted through the urethra. It is used as an alternative to prostatectomy in patients with extensive disease or those who are not fit enough to undergo radical prostatectomy to remove tissue that is blocking urine flow. This is often referred to as a channel TURP.