Prostate Cancer: Causes and Treatments Morganstern Urology, P.C., Atlanta, GA
Prostate cancer is characterized by the growth within the gland of a malignant tumor; medically known as an “adenocarcinoma.” This tumor is defined as a “primary cancer” because its growth is triggered by an event within the prostate, not by the invasion of cancerous cells from some other part of the body. Most often, growth of an adenocarcinoma occurs first in the outer rear region of the prostate. As growth continues, the tumor may spread deep into the interior of the gland. In time, the malignancy may establish footholds in the various organs surrounding the prostate, eventually spreading to many other parts of the body.
The pace at which prostate cancer spreads appears to depend upon the individual patient and the nature of the tumor itself. In a 1989 study by researchers at University Hospital, Uppsala, Sweden, of a group of 223 men diagnosed with early-stage prostate cancer but not subsequently treated, the disease showed signs of having spread in 62 men during an average period of six and a half years following diagnosis. The disease was most widespread in patients diagnosed with larger and more palpable tumors, those easier to identify by touch during digital rectal examination.
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What Causes Prostate Cancer?
Patients often ask us what caused their prostate cancer. Unfortunately, there is no definitive answer; not too surprising since, despite recent advances in medical science, a specific cause cannot be identified in more than half of all cancer types. In cases where a cause has been located scientifically, smoking is the most frequent culprit.
In prostate cancer, there is some evidence that a diet high in fat may increase the odds. However, no link has yet been found between prostate cancer and anything else you personally control, such as alcohol, tobacco, or other drugs. There is some evidence that men exposed in the workplace to cadmium, a fairly toxic metallic element, are at slightly greater risk. Cadmium is present in storage battery manufacture, metal alloys, and electroplating. Men working in these industries should be careful to follow safety rules, and to have periodic prostate examinations/screenings.
Genetics may be a factor; too, as revealed by statistics that suggest men with a father or brother who had prostate cancer have a considerably higher risk for the disease. Black Americans have the highest known incidence of prostate cancer in the world. New cases are reported in Black Americans at a rate per 100,000 almost double that of Caucasians. Genetics might also be a factor, but so could environmental conditions or even a combination of the two.
Hormones play a significant role. Testosterone stimulates malignant cell growth in the prostate. Prostate cancer is rare in men who were castrated before the usual onset age for the disease. As we’ve seen, testosterone has the same effect in stimulating benign prostate enlargement. However, there is no evidence of any other connection between prostate cancer and BPH.
Early in 1993, two studies were reported in the Journal of the American Medical Association suggesting that men who had had vasectomies as long as twenty or so years ago have shown an increased incidence of prostate cancer. However, these studies are at odds with two earlier investigations indicating no such relationship. If you have had a vasectomy, don’t panic. No study has yet demonstrated without qualification any increased risk of death from prostate cancer in vasectomized men. Earlier concerns about a possible relationship between vasectomy and cardiovascular disease were never substantiated either. Even so, taking the recent studies into account, the American Urological Association recommends that all men who had vasectomies more than twenty years ago or who were more than 40 at the time of a vasectomy should have an annual digital rectal examination and the PSA test. We recommend the same plan to any patient whose close family relatives have a prostate cancer history. The American Urological Association is NOT recommending against vasectomy.
Finally, some studies suggest a possible relationship between prostate cancer and sexual behavior. A study at the University of Illinois suggested that a pattern of life-long sexual repression was linked to increased incidence of prostate cancer theorizing that a buildup of male hormones in the prostate might be the cause. While the link between prostate cancer and lack of sex is not yet fully proved, there is a known connection between sexual abstinence and some prostate problems.
Who Gets Prostate Cancer?
Prostate cancer strikes men in all walks of life. Some recent cases have included Senator Robert Dole, the senate minority leader; Francois Mitterrand, president of France; Stan Musial, the great St. Louis Cardinals slugger; Steven Ross, chairman of the media giant, Time-Warner; Frank Zappa, the popular rock star; and Anthony Salerno, former capo of the Genovese organized crime family.
What Are My Chances?
At this time, new prostate cancer cases are diagnosed among American males in excess of 130,000 cases a year and that total is rising. After skin cancer, prostate cancer is the most common cancer among men in the United States. It is well ahead of the third most common type, lung cancer, which has about 100,000 new cases a year.
Based on these statistics, your chances as an American male of developing prostate cancer are about 1 in 11, about the same rate as for women who develop breast cancer. There is no hard evidence but good reason to suspect prostate cancer is actually more common in men than breast cancer is in women. Breast cancer received extensive coverage by the media and women have been strongly encouraged to undergo annual mammographies. Prostate cancer and the need for the digital rectal examination have not received nearly as much attention. Consequently, many cases of prostate cancer may be undiagnosed.
Your chances of getting prostate cancer increase significantly with age. In men under 50, the disease is rare. However, the number of cases in younger men may increase chiefly because of improved diagnoses. As many as 30 percent of all men above 50 harbor some cancerous cells in the prostate, but only 1 percent of these men will develop cancer itself. About 80 percent of all prostate cancer cases are diagnosed in men 65 and older. Cancerous cells are detected in the prostate in most men in their eighties, although octogenarians usually die from heart disease, pneumonia, and other disorders of old age, not from prostate cancer.
The American Cancer Society predicted about 34,000 American men would die from prostate cancer in 1992. That is about a third of the rate for men who die from lung cancer, but ahead of the colon and rectal cancer death rates. The total deaths annually from prostate cancer has been increasing, mainly because of a growing population of older American men. Because of their age, they are at increased risk for prostate cancer, not from any failure of medicine or the presence of anything new in the environment.
Your overall chances with prostate cancer are dependent on how far the disease has progressed when it is first diagnosed. The earlier the detection, the easier and more effective the treatment. The following section covers prostate cancer development and is the basis for later sections that discuss treatment.
Treating Prostate Cancer
This section described various methods for treating prostate cancer; regardless of its stage. You’ll be told about treatments most often used at each of the four stages. In general, these cancer treatments are accepted by the American medical community or are now undergoing scientific investigation:
- Surgery
- Radiation Therapy
- Drugs
- Hyperthermia
- Immunotherapy
- Gene Therapy
As with most cancers, prostate cancer treatment has been limited mainly to the first three approaches above – surgery, radiation therapy, and drugs (chemotherapy). Prostate cancer treatment programs commonly employ a combination of one or more of these three. The other treatments – hyperthermia, immunotherapy, and gene therapy – are still experimental, but may prove valuable in treating prostate and other cancers.
Prostate Cancer Surgery
Prostate surgery involves cutting out the cancerous tissue with a scalpel or, more recently, a laser. Completely removing cancerous tissue eliminates the source of an existing malignancy, although it is possible a new malignancy could develop on its own in the remaining healthy tissue. Implicit in surgery is possible surgical damage to healthy tissue and that the surgery may not remove entirely all the cancerous cells.
Castration – removing the testicles – is sometimes necessary in prostate cancer treatment. It is a surgical procedure whose object is to reduce testosterone production. Castration is discussed below in connection with drugs that treat prostate cancer.
To ensure complete removal of malignant tissue, thus eliminating the possibility of a new cancer developing on its own in healthy tissue, most urologists favor radical prostatectomy, removal of the entire prostate gland.
Robotic prostate surgery has proven to be safer and more effective. In this technique, a urologist programs the desired pattern of surgical cuts into a computer that controls a robot surgical device. The information is obtained from an earlier scan of the patient’s internal anatomy. This technique extends the technology of navigation guidance systems that control cruise missile flight paths. Robot surgery provides more precise and deliberate cutting, and may make radical prostatectomies considerably easier on patients, reducing undesirable side effects, including impotence.
In a radical perineal prostatectomy for prostate cancer, the entire prostate gland is removed along with nearby tissues when there is any reason to suspect possible malignancy. This procedure offers the possibility of a permanent cure when the malignant tumor is sufficiently localized, but almost always causes impotence. Because a perineal prostatectomy is less physically affecting than a retropubic prostatectomy, it is sometimes used with older patients and those in poor health who may be higher surgical risks.
During the radical retropubic prostatectomy for prostate cancer, in order to provide additional reassurance, nearby pelvic lymph nodes are also removed. The operation is safe, although somewhat harder on a patient than perineal prostatectomy. Retropubic prostatectomy has some advantages over perineal prostatectomy as to impotence and incontinence. An additional factor favoring the retropubic procedure is that perineal prostatectomy is an older operation and younger urologists may lack training or experience in performing it.
With radical retropubic prostatectomy, there is a possibility of both impotence and incontinence. In the past several years, a new nerve-sparing surgical technique has been employed with retropubic prostatectomy that is said to reduce the possibility of impotence. This technique minimizes damage to the nerve bundle that controls erections. However, the effectiveness of this new procedure has not been well established. Regardless, treatments do exist for any impotence that follows radical prostatectomy. Fortunately, incontinence after a radical retropubic prostatectomy is found in only a few cases.
Sometimes, transurethral resection is used to remove cancerous prostate tissues. TURP does not remove the whole malignant tumor, so it does not provide a permanent cure. To some extent, it is used to provide relief from the voiding problems caused by prostate cancer, to obtain tissue samples for biopsy, and, as noted below, experimentally in association with laser surgery.
Laser surgery is being used to treat benign prostate enlargement. Laser surgery is also being investigated experimentally for surgical treatment of prostate cancer. However, in connection with prostate cancer, it has attracted less attention than in BPH, owing to a prevailing belief among urologists that cancerous prostates should be removed entirely. That view tends to eliminate one of the major advantages of laser surgery, it’s highly accurate cutting. One approach now being considered is a combination of transurethral resection and laser surgery. In the first step of this technique, most of the prostate tissue is removed using a TURF In the second step, all remaining prostate tissue is accurately removed with a laser beam guided by ultrasound imaging.
Cryosurgery and ultrasound surgery are both being investigated for prostate cancer treatment. Potentially, cryosurgery is easier on patients than conventional cutting. In ultrasound surgery, transrectal ultrasound, along with a computer in the procedure under study, first defines the tissue areas to be removed, then destroys malignant tissue with ultrasound bombardment. This technique also has the potential of making things easier on the patient.
As with most cancers, prostate cancer treatment has been limited mainly to the first three approaches above – surgery, radiation therapy, and drugs (chemotherapy). Prostate cancer treatment programs commonly employ a combination of one or more of these three.
Radiation Therapy in Prostate Cancer Treatment
In radiation therapy, high-energy subatomic particles bombard and destroy prostate cancer cells. But radiation is inherently dangerous and always kills nearby healthy cells besides targeted cancerous cells. With a skilled radiologist, with lower levels of radiation, and with proper scheduling of treatment, “collateral” damage to healthy cells can be minimized. And when enough healthy cells manage to survive the radiation treatment, damaged healthy tissue can regenerate.
Radiation is scary to a general public conditioned by events such as the Chernobyl nuclear disaster in the Ukraine. However, there is no threat to life with the radiation levels used in standard medical practice.
Two methods are used to irradiate the prostate. In external-beam radiotherapy, the prostate is subjected to a brief period of bombardment by a focused beam of x-rays from an external machine. External-beam radiotherapy has been in general use for prostate cancer since the sixties. Radiation is applied outpatient, typically in a series of up to five-day-a-week sessions, usually conducted for about seven weeks. This treatment is absolutely painless.
A newer technique is where tiny capsules containing a radioactive substance are implanted surgically into the prostate tumor. This implantation is done under anesthesia with minimal discomfort. Known technically as interstitial radiation therapy, seed implantation generally uses Iodine 125 as its radioactive source. Once implanted, the seeds emit a continuous stream of radiation strong enough to kill cancerous cells for about one year. These seeds remain permanently; while there is always some continuing radiation, no harm or discomfort is caused to the patient.
There are side effects from both external-beam radiotherapy and seed implantation. In the former; about 25 percent of patients report symptoms including fatigue, nausea, diarrhea, frequent and painful urination, skin eruptions, and rectal bleeding or discomfort. In about all but 10 percent of patients, these symptoms usually disappear in less than three months. Drugs can help control some of these side effects. External-beam radiotherapy causes permanent impotence in from 20 to 40 percent of all patients.
Seed implantation, however, has considerably fewer and milder side effects, although some men do experience mild bladder or rectal irritations. Impotence and incontinence are reported at less than 10 percent and 5 percent, respectively, when Iodine 125 treatment is used. As will be discussed later; seed implantation is usually limited to early stages of prostate cancer.
In all radiation therapy, the possibility exists that some cancerous cells may not be destroyed. However some studies have shown in about two out of three patients a disease-free, five-year survival rate with external-beam radiotherapy, and about the same for patients treated with seed implantation in combination with drugs. Generally, radiation therapy is a good choice for some men who prefer not to have surgery, or who, because of age or general physical condition, are not good surgery candidates.
A promising recent development is Palladium 103 seeds as a radioactive source, along with Iodine 125, sometimes also with X ray. Palladium treatment, which can be done outpatient, supported by ultrasound to guide the seed placement, appears to cause virtually no incontinence and a very low occurrence of impotence. Gus, a patient diagnosed with early prostate cancer; was playing golf two days after this procedure. He requested it after he learned that two friends who’d had radical prostatectomies have experienced impotence, one became incontinent.
Prostate Cancer: Role of Drugs
Medical science has not yet developed a miracle drug that cures prostate cancer. Still, drugs do play an increasingly important and effective role in prostate cancer treatment. Drug therapy takes two-forms: colon hormonal therapy and chemotherapy. The former, based on the pioneering work of Nobel Laureate Dr. Charles B. Huggins, has been used for about 50 years. The latter is still experimental.
Hormonal Therapy
Treatments for reducing testosterone production or blocking activity of this hormone can retard significantly the growth of prostate cancer in some patients, even reducing significantly the size of existing tumors in others. As is the case with benign prostate enlargement, very early it was recognized that castration would help men with prostate cancer. Although castration is surgery, it nevertheless represents a form of hormonal therapy.
Castration, or orchiectomy, involves the removal of the testicles and may even be performed outpatient with a local anesthetic. Neither the procedure itself nor recovery from it is painful. Contrary to common belief, removing the testicles does not always result in loss of erections. Even in a castrated male, there are ways to deal with impotence.
Today, castration is rarely performed on men who have benign prostate enlargement, but it still has some role in prostate cancer treatment. It is widely employed in testicular cancer treatment. The continuing use of castration to treat prostate cancer is due principally to its obvious effectiveness in eliminating testosterone production, except for the small amount of the hormone produced in the adrenal glands.
Following orchiectomy, some men obtain silicone testicle implants for cosmetic purposes. These implants have aroused widespread public controversy in connection with silicone breast implants in women. Concern about the breast implants has arisen because of silicone leakage. But in testicle implants, liquid silicone is not used, so there have been few problems with them.
Of course, not all men opt for testicle implants, since there are few circumstances where the appearance of the genitals is of much concern. In others, though, the missing testicles raise psychological problems like those experienced by women after mastectomy.
Fortunately, today there are increasingly effective alternatives to castration. One possibility is female hormones, including estrogen to treat prostate cancer. However; this hormone causes undesirable side effects. Therefore, there is increasing preference for “luteinizing hormone-releasing hormone” therapy, or LHRH.
Luteinizing hormone-releasing therapy involves a drug known as a LHRH analog. This substance blocks chemically the action of testosterone produced in the testicles. LHRH results are similar to castration and estrogen therapy, but with few of their inherent disadvantages.
Typically, patients treated with LHRH are injected about once a month at their urologist’s office. Some men have experienced hot flashes, general pain and malaise, and gastrointestinal side effects. Most of these problems can be controlled with appropriate drugs, but impotence and libido loss are also possible. A number of LHRH analogs have been tested, but most current interest centers on a drug known as leuprolide, sold under the name Lupron.
LHRH therapy is often used in combination with antiandrogen therapy. Androgens are drugs that block the small additional amounts of testosterone produced in the adrenal glands. Flutamide, sold under the name Eulexin, has been one of the most frequently prescribed antiandrogens. This drug is also used to treat BPH and had certain side effects. Other antiandrogens that have shown promise include goserelin acetate, sold under the name Zoladex, and aminoglutithamide, sold as Cytraden.
When LHRH and antiandrogen therapy are used in combination, side effects can include nausea, diarrhea, hot flashes, and vomiting. Impotence is also possible. Combination therapy, however; is often considerably more effective than LHRH therapy alone.
The pace of hormonal therapy research has been accelerating, and new drugs are coming to our attention almost daily. One interesting drug reported to have possible value in treating prostate and other cancers is mifepristine, a drug developed in France, sold under the name RU-486. The drug is being sold for family planning purposes in several countries.
Chemotherapy
Chemotherapy is not yet a major factor in prostate cancer treatment. Chemotherapy involves administration of highly potent drugs that lower the rate of cell growth within the body. When chemotherapy drugs are injected into the bloodstream, they circulate throughout the body and harm cancerous and healthy cells alike. However, the damage is greatest in the cells growing the fastest, including cancerous cells and those cells that govern hair growth.The pace of hormonal therapy research has been accelerating, and new drugs are coming to my attention almost daily.
To date, many chemotherapy drugs have been tested on prostate cancer. While many of them have been shown to be effective in treating other forms of cancer, so far, none has proven very effective on prostate cancer. One problem may be the failure of many of them to reach the prostate effectively through the bloodstream. Chemotherapy drugs are also associated with many unpleasant side effects, including nausea, fatigue, body pain, and hair loss. Nonetheless, the possibility does exist that more effective prostate cancer chemotherapy agents will eventually be developed.
Hyperthermia
Hyperthermia employing localized heat produced by microwaves has shown promise in treating benign prostate enlargement. Encouraging results are also indicated in some patients with certain types of prostate cancer. The advantage of effective hyperthermia in treating prostate cancer would be similar to that suggested for BPH, an easy-to-tolerate, nonsurgical procedure that can be performed outpatient.
Immunotherapy
Immunotherapy strengthens the body’s natural immune system. Over thousands of years, the human body has developed a defense mechanism, operating through agents in the bloodstream, that identifies and kills invading organisms. Being out of the ordinary, cancerous cells may appear to be undesirable invaders to the immune system.
In immunotherapy, certain drugs have been found to improve this identification and killing process. Considerable attention has centered on supplementation of a drug known as interleukin-2, a complex substance produced naturally by the body’s immune system. This drug promotes the growth of additional immune cells in the bloodstream. Lymphokine-activated killer T cells are also being investigated.
Vaccines are also at an early stage of study and may prevent the recurrence of prostate and other cancers in patients who have previously been treated for malignancies. Tumor tissue is obtained by biopsy from an individual patient and a vaccine is produced in the laboratory that can later be injected into the patient. Thus, a potential exists for protecting a patient with a vaccine prepared from his own body.
So far, results with immunotherapy are limited and hopes should not be raised prematurely for a major new approach to treating cancer, including prostate cancer. Nevertheless, given the role played by the immune system in disease prevention and control, this area of research has long-range promise.
Gene Therapy
Gene therapy in cancer treatment involves altering DNA, the basic chemical substance governing growth and function of every cell in your body. By using genetic engineering, the possibility exists to manufacture and introduce into the body new genes that may make cells more resistant to the triggering of cancer or that make cells better cancer fighters when a cancer gets underway.
While gene therapy is still in its early stage, in the long-run, the possibility may exist for an effective end to the prostate cancer problem. A development with major implications on gene therapy is the ongoing Genome Project. In this massive undertaking, scientists are mapping the entire DNA structure of the human body. Once completed, results may offer a workable means of pinpointing and altering areas associated with each type of cancer.
