Key Terms: Antiandrogen, Benign Prostate Hyperplasia, Brachytherapy, Gleason Grading System, Granulocyte/macrophage colony stimulating factor, Histopathology, Luteinizing hormone releasing hormone (LHRH) agonist, Orchiectomy, Prostate-Specific Antigen, Radical Prostatectomy.
Definition
Prostate cancer is a disease in which cells in the prostate gland become abnormal and start to grow uncontrollably, forming tumors.
Description
Prostate cancer is a malignancy of one of the major male sex glands. Along with the testicles and the seminal vesicles, the prostate secretes the fluid that makes up semen. The prostate is about the size of a walnut and lies just behind the urinary bladder. A tumor in the prostate interferes with proper control of the bladder and normal sexual functioning. Often the first symptom of prostate cancer is difficulty in urinating. However, because a very common, non-cancerous condition of the prostate, benign prostatic hyperplasia (BPH), also causes the same problem, difficulty in urination is not necessarily due to cancer.
Cancerous cells within the prostate itself are generally not deadly on their own. However, as the tumor grows, some of the cells break off and spread to other parts of the body through the lymph or the blood, a process known as metastasis. The most common sites for prostate cancer to metastasize are the seminal vesicles, the lymph nodes, the lungs, and various bones around the hips and the pelvic region. The effects of these new tumors are what can cause death.
Demographics
Prostate cancer is the most commonly diagnosed malignancy among adult males in Western countries. Although prostate cancer is often very slow growing, it can be aggressive, especially in younger men. Given its slow growing nature, many men with the disease die of other causes rather than from the cancer itself.
Prostate cancer affects African-American men twice as often as white men; the mortality rate among African-Americans is also two times higher. African-Americans have the highest rate of prostate cancer of any world population group.
Causes and Symptoms
The precise cause of prostate cancer is not known. However, there are several known risk factors for disease including age over 55, African-American heritage, a family history of the disease, occupational exposure to cadmium or rubber, and a high-fat diet. Men with high plasma testosterone levels may also have an increased risk for developing prostate cancer.
Frequently, prostate cancer has no symptoms and the disease is diagnosed when the patient goes for a routine screening examination. However, when the tumor is big or the cancer has spread to the nearby tissues, the following symptoms may be seen:
- weak or interrupted flow of the urine
- frequent urination (especially at night)
- difficulty starting urination
- inability to urinate
- pain or burning sensation when urinating
- blood in the urine
- persistent pain in lower back, hips, or thighs (bone pain)
- painful ejaculation
Diagnosis
Prostate cancer is curable when detected early. Yet the early stages of prostate cancer are often asymptomatic, so the disease often goes undetected until the patient has a routine physical examination. Diagnosis of prostate cancer can be made using some or all of the following tests.
Digital Rectal Examination (DRE)
In order to perform this test, the doctor puts a gloved and lubricated finger (digit) into the rectum to feel for any lumps in the prostate. The rectum lies just behind the prostate gland, and a majority of prostate tumors begin in the posterior region of the prostate. If the doctor does detect an abnormality, he or she may order more tests in order to confirm these findings.
Blood Tests
Blood tests are used to measure the amounts of certain protein markers, such as prostate-specific antigen (PSA), found circulating in the blood. The cells lining the prostate generally make this protein and a small amount can be detected normally in the bloodstream. In contrast, prostate cancers produce a lot of this protein, significantly raising the circulating levels. A finding of a PSA level higher than normal for the patient's age group therefore suggests that cancer is present.
Transrectal Ultrasound
A small probe is placed in the rectum and sound waves are released from the probe. These sound waves bounce off the prostate tissue and an image is created. Since normal prostate tissue and prostate tumors reflect the sound waves differently, the test is an efficient and accurate way to detect tumors. Though the insertion of the probe into the rectum may be slightly uncomfortable, the procedure is generally painless and only takes 20 minutes.
Prostate Biopsy
If cancer is suspected from the results of any of the above tests, the doctor will remove a small piece of prostate tissue with a hollow needle. This sample is then checked under the microscope for the presence of cancerous cells. Prostate biopsy is the most definitive diagnostic tool for prostate cancer, and this procedure is done quickly and with little pain or discomfort.
Prostate cancer can also be diagnosed based on the examination of the tissue removed during a transurethral resection of the prostate (TURP). This procedure is performed to help alleviate the symptoms of BPH, a benign enlargement of the prostate. Like a biopsy, this is a definitive diagnostic method for prostate cancer.
X Rays and Imaging Techniques
A chest x ray may be ordered to determine whether the cancer has spread to the lungs. Imaging techniques (such as computed tomography (CT) scans and magnetic resonance imaging (MRI)), where a computer is used to generate a detailed picture of the prostate and areas nearby, may be done to get a clearer view of the internal organs. A bone scan may be used to check whether the cancer has spread to the bone.
Treatment Team
Prostate cancer is often treated by a team of specialists including a urologist (who may or may not perform surgery), a surgeon (if surgical treatment is used and it is not performed by the urologist), a medical oncologist, and, if radiation therapy is used, a radiation oncologist.
Clinical Staging, Treatments, and Prognosis
Once cancer is detected during the microscopic examination of the prostate tissue during a biopsy or TURP, doctors will determine two different numerical scores that will help define the patient's treatment and prognosis.
Tumor Grading
Initially, the pathologist will grade the tumor based on his or her examination of the biopsy tissue. The pathologist scores the appearance of the biopsy sample using the Gleason system. This system uses a scale of one to five based on the sample's similarity or dissimilarity to normal prostate tissue. If the tissue is very similar to normal tissue, it is still well differentiated and given a low grading number, such as one or two. As the tissue becomes more and more abnormal (less and less differentiated), the grading number increases, up to five. Less differentiated tissue is considered more aggressive and more likely to be the source of metastases.
The Gleason grading system is best predictive of the prognosis of a patient if the pathologist gives two scores to a particular sample—a primary and a secondary pattern. The two numbers are then added together and that is the Gleason score reported to the patient. Thus, the lowest Gleason score available is two (a primary and secondary pattern score of one each). A typical Gleason score is five (which can be a primary score of two and a secondary score of three or visa-versa). The highest score available is 10, with a pure pattern of very undifferentiated tissue, that is, of grade five. The higher the score, the more abnormal behavior of the tissue, the greater the chance for metastases, and the more serious the prognosis after surgical treatment. A study found that the ten-year cancer survival rate without evidence of disease for grade two, three, and four cancers is 94% of patients. The rate is 91% for grade five cancers, 78% for grade six, 46% for grade seven, and 23% for grade eight, nine, and ten cancers.
Cancer Staging
The second numeric score determined by the doctor will be the stage of the cancer, which takes into account the grade of the tumor determined by the pathologist. Based on the recommendations of the American Joint Committee on Cancer (AJCC), two kinds of data are used for staging prostate cancer. Clinical data is based on the external symptoms of the cancer, while histopathological data is based on surgical removal of the prostate and examination of its tissues. Clinical data is most useful to make treatment decisions, while pathological data is the best predictor of prognosis. For this reason, the staging of prostate cancer takes into account both clinical and histopathologic information. Specifically, doctors look at tumor size (T), lymph node involvement (N), the presence of visceral (internal organ) involvement (metastasis = M), and the grade of the tumor (G).
The classification of tumor as T1 means the cancer that is confined to the prostate gland and the tumor that is too small to be felt during a DRE. T1 tumors are often found after examination of tissue removed during a TURP. The T1 definition is subdivided into those cancers that show less than 5% cancerous cells in the tissue sample (T1a) or more than 5% cancerous cells in the tissue sample (T1b). T1c means that the biopsy was performed based on an elevated PSA result. The second tumor classification is T2, where the tumor is large enough to be felt during the DRE. T2a indicates that only the left or the right side of the gland is involved, while T2b means both sides of the prostate gland has tumor.
With a T3 tumor, the cancer has spread to the connective tissue near the prostate (T3a) or to the seminal vesicles as well (T3b). T4 indicates that cancer has spread within the pelvis to tissue next to the prostate such as the bladder's sphincter, the rectum, or the wall of the pelvis. Prostate cancer tends to spread next into the regional lymph nodes of the pelvis, indicated as N1. Prostate cancer is said to be at the M1 stage when it has metastasized outside the pelvis in distant lymph nodes (M1a), bone (M1b) or organs such as the liver or the brain (M1c). Pain, weight loss, and fatigue often accompany the M1 stage.
The grade of the tumor (G) can be assessed during a biopsy, TURP surgery, or after removal of the prostate. There are three grades recognized: G1, G2, and G3, indicating the tumor is well, moderately, or poorly differentiated, respectively. The G, LN, M descriptions are combined with the T definition to determine the stage of the prostate cancer.
- Stage I prostate cancer comprises patients who are T1a, N0, M0, G1.
- Stage II includes a variety of condition combinations including T1a, N0, M0, G2, 3 or 4; T1b, N0, M0, Any G; T1c, N0, M0, Any G; T1, N0, M0, Any G or T2, N0, M0, Any G.
- Stage III prostate cancer occurs when conditions are T3, N0, M0, any G.
- Stage IV is T4, N0, M0, any G; any T, N1, M0, any G; or any T, any N, M1, Any G.
Prognosis
The prognosis for cancers at Stages I and II is very good. For men treated with stage I or stage II disease, over 95% are alive after five years. Although the cancers of Stage III are more advanced, the five-year prognosis is still good, with 70% of men diagnosed at this stage still living. The spread of the cancer into the pelvis (T4), lymph (N1), or distant locations (M1) are very significant events, as the five-year survival rate drops to 30% for Stage IV.
Treatment Options
The doctor and the patient will decide on the treatment mode after considering many factors. For example, the patient's age, the stage of the disease, his general health, and the presence of any co-existing illnesses have to be considered. In addition, the patient's personal preferences and the risks and benefits of each treatment protocol are also taken into account before any decision is made.
Surgery
For stage I and stage II prostate cancer, surgery is the most common method of treatment because it theoretically offers the chance of completely removing the cancer from the body. Radical prostatectomy involves complete removal of the prostate. The surgery can be done using a perineal approach, where the incision is made between the scrotum and the anus, or using a retropubic approach, where the incision is made in the lower abdomen. Perineal approach is also known as nerve-sparing prostatectomy, as it is thought to reduce the effect on the nerves and thus reduce the side effects of impotence and incontinence. However, the retropubic approach allows for the simultaneous removal of the pelvic lymph nodes, which can give important pathological information about the tumor spread.
The drawback to surgical treatment for early prostate cancer is the significant risk of side effects that impact the quality of life of the patient. Even using nerve-sparing techniques, studies by the National Cancer Institute (NCI) found that 60% to 80% of men treated with radical prostatectomy reported themselves as impotent (unable to achieve an erection sufficient for sexual intercourse) two years after surgery. This side effect can be sometimes countered by prescribing sildenafil citrate (Viagra). Furthermore, 8% to 10% of patients were incontinent in that time span. Despite the side effects, the majority of men were reported as satisfied with their treatment choice. Additionally, there is some evidence that the skill and the experience of the surgeon are central factors in the ultimate side effects seen.
A second method of surgical treatment of prostate cancer is cryosurgery, or cryotherapy. Guided by ultrasound, surgeons insert up to eight cryoprobes through the skin and into close proximity with the tumor. Liquid nitrogen (temperature of -320.8 degrees F, or -196 C) is circulated through the probe, freezing the tumor tissue. In prostate surgery, a warming tube is also used to keep the urethra from freezing. Patients currently spend a day or two in the hospital following the surgery, but it could be an outpatient procedure in the near future. Recovery time is about one week. Side effects have been reduced in recent years, although impotence still affects almost all who have had cryosurgery for prostate cancer. Cryo-surgery is considered a good alternative for those too old or sick to have traditional surgery or radiation treatments or when these more traditional treatments are unsuccessful. There is limited amount of information about the long-term efficacy of this treatment for prostate cancer.
RADIATION THERAPY Radiation therapy involves the use of high-energy x rays to kill cancer cells or to shrink tumors. It can be used instead of surgery for stage I and II cancer. The radiation can either be administered from a machine outside the body (external beam radiation), or small radioactive pellets can be implanted in the prostate gland in the area surrounding the tumor, called brachytherapy or interstitial implantation. Pellets containing radioactive iodine (I-125), palladium (Pd 103), or iridium (Ir 192) can be implanted on an outpatient basis, where they remain permanently. The radioactive effect of the seeds last only about a year.
The side effects of radiation can include inflammation of the bladder, rectum, and small intestine as well as disorders of blood clotting (coagulopathies). Impotence and incontinence are often delayed side effects of the treatment. A study indicated that bowel control problems were more likely after radiation therapy when compared to surgery, but impotence and incontinence were more likely after surgical treatment. Long-term results with radiation therapy are dependent on stage. A review of almost 1,000 patients treated with megavoltage irradiation showed 10-year survival rates to be significantly different by T-stage: T1 (79%), T2 (66%), T3 (55%), and T4 (22%). There does not appear to be a large difference in survival between external beam or interstitial treatments.
Hormone Therapy
Hormone therapy is commonly used when the cancer is in an advanced stage and has spread to other parts of the body, such as stage III or stage IV. Prostate cells need the male hormone testosterone to grow. Decreasing the levels of this hormone or inhibiting its activity will cause the cancer to shrink. Hormone levels can be decreased in several ways. Orchiectomy is a surgical procedure that involves complete removal of the testicles, leading to a decrease in the levels of testosterone. Another method tricks the body by administering the female hormone estrogen. When estrogen is given, the body senses the presence of a sex hormone and stops making the male hormone testosterone. However, there are some unpleasant side effects to hormone therapy. Men may have "hot flashes," enlargement and tenderness of the breasts, or impotence and loss of sexual desire, as well as blood clots, heart attacks, and strokes, depending on the dose of estrogen. Another side effect is osteoporosis, or loss of bone mass leading to brittle and easily fractured bones.
Watchful Waiting
Watchful waiting means no immediate treatment is recommended, but doctors keep the patient under careful observation. This is often done using periodic PSA tests. This option is generally used in older patients when the tumor is not very aggressive and the patients have other, more life-threatening, illnesses. Prostate cancer in older men tends to be slow-growing. Therefore, the risk of the patient dying from prostate cancer, rather than from other causes, is relatively small.
Alternative and Complementary Therapies
Alternative treatments that have been found helpful in coping with the emotional stress associated with prostate cancer include meditation, guided imagery, and relaxation techniques. Acupuncture is effective in relieving pain in some patients.
A variety of herbal products have been used to treat prostate cancer, including various compounds used in traditional Chinese medicine as well as single agents like Reishi mushrooms (Ganoderma lucidum). One herbal compound that was under investigation by the National Center for Complementary and Alternative Medicine (NCCAM) as a possible treatment for prostate cancer was PC-SPES, a mixture of eight herbs adapted from traditional Chinese medicine. In the summer of 2002, however, NCCAM put its studies of PC-SPES on hold when the Food and Drug Administration (FDA) determined that samples of the product were contaminated with undeclared prescription drug ingredients. PC-SPES was withdrawn from the American market in late 2002.
Coping With Cancer Treatment
The treatment process for prostate cancer can be a physically and emotionally exhausting time. Here are six general suggestions that can help make the process easier. Patients should:
- put their faith and trust in their doctors once a treatment course has been chosen
- remember that a patient is never without power and rights during the course of treatment
- put practical affairs in order
- closely monitor each step of the treatment
- keep close family and friends informed and delegate responsibilities as necessary
- work to make visits pleasant and comfortable
- be careful to eat, sleep, exercise, and conduct daily activities in a healthy manner
Clinical Trials
Patients with extraprostatic disease are suitable candidates for clinical trials. One trial is the testing of a vaccine (GVAX) that causes the body to mount an immune response against all prostate cells. As the prostate is a nonessential organ, the destruction of the normal cells with the tumor cells is not a problem. The vaccine was made using cancer cells from a tumor that had been genetically engineered to express granulocyte/macro-phage colony-stimulating factor (GM-CSF), a potent activator of the entire immune system. The additional protein jumpstarted the immune response against the prostate cells upon vaccination and resulted in anti-tumor immune response.
Other trials for prostate cancer include evaluation of combination therapies, such as postoperative radiation delivery, use of cytotoxic agents, and hormonal treatment using luteinizing hormone-releasing hormone (LHRH) agonists and/or antiandrogens to shut down the growth of the hormone-dependent tumors. Other drugs that are being tested as of 2003 are chemoprotective agents like amifostine (Ethyol), which are given to prostate cancer patients to counteract the harmful side effects of radiation treatment.
Prevention
Because the cause of the cancer is not known, there is no definite way to prevent prostate cancer. Given its common occurrence and the low cost of screening, the American Cancer Society (ACS) and the National Comprehensive Cancer Network (NCCN) recommends that all men over age 40 have an annual rectal exam and that men have an annual PSA test beginning at age 50. African-American men and men with a family history of prostate cancer, who have a higher than average risk, should begin annual PSA testing even earlier, starting at age 45.
However, mandatory screening for prostate cancer is controversial. Because the cancer is so slow growing, and the side effects of the treatment can have significant impact on patient quality of life, some medical organizations question the wisdom of yearly exams. Some organizations have even noted that the effect of screening is discovering the cancer at an early stage when it may never grow to have any outward effect on the patient during this lifetime. Nevertheless, the NCI reports that the current aggressive screening methods have achieved a reduction in the death rate of prostate cancer of about 2.3% for African-Americans and about 4.6% for Caucasians since the mid-1990s, with a 20% increase in overall survival rate during that period.
A low-fat diet may slow the progression of prostate cancer. To reduce the risk or progression of prostate cancer, the American Cancer Society recommends a diet rich in fruits, vegetables and dietary fiber, and low in red meat and saturated fats.
Questions to Ask the Doctor
- How do my age, general health, and other medical conditions affect my treatment choices?
- What are the T, N, and M stages of my cancer and how do they influence my treatment options?
- How do the Gleason score of my cancer and my blood prostate-specific antigen (PSA) level predict my outlook for survival and affect treatment options?
- What are the likely side effects of each proposed therapy and how will they affect my quality of life?
- What can be done to help manage the side effects of treatment?
Special Concerns
The availability of an early detection system for prostate cancer with the development of the PSA serum test has complicated the treatment of this disease. Early detection of an often slow-growing cancer, where treatment can significantly impact the quality of life of the patient, can be complicated. Long-term studies are currently in progress that should provide the first real quantitative information about the relative efficacy of the different treatment options, the actual occurrence of side effects, and the comparative benefits of watchful waiting treatment compared with more aggressive action.
Resources
Books
Beers, Mark H., MD, and Robert Berkow, MD, editors. "Prostate Cancer." Section 17, Chapter 233 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.
Carroll, Peter R., et al. "Cancer of the Prostate." In Cancer Principles and Practice of Oncology, edited by Devita, Vincent T., et al. Philadelphia: Lippincott Williams & Wilkins, 2001.
Wainrib, Barbara R., and Sandra Haber. Men, Women, and Prostate Cancer. Oakland, CA: New Harbinger Productions, Inc., 2000.
Periodicals
Alimi, D., C. Rubino, E. Pichard-Leandri, et al. "Analgesic Effect of Auricular Acupuncture for Cancer Pain: A Randomized, Blinded, Controlled Trial." Journal of Clinical Oncology 21 (November 15, 2003): 4120–4126.
Chang, S. S. "Exploring the Effects of Luteinizing Hormone-Releasing Hormone Agonist Therapy on Bone Health: Implications in the Management of Prostate Cancer." Urology 62 (December 22, 2003): 29–35.
de la Fouchardiere, C., A. Flechon, and J. P. Droz. "Coagulopathy in Prostate Cancer." Netherlands Journal of Medicine 61 (November 2003): 347–354.
Dziuk, T., and N. Senzer. "Feasibility of Amifostine Administration in Conjunction with High-Dose Rate Brachytherapy." Seminars in Oncology 30 (December 2003): 49–57.
Hsieh, K., and P. C. Albertsen. "Populations at High Risk for Prostate Cancer." Urological Clinics of North America 30 (November 2003): 669–676.
Linares, L. A., and D. Echols. "Amifostine and External Beam Radiation Therapy and/or High-Dose Rate Brachytherapy in the Treatment of Localized Prostate Carcinoma: Preliminary Results of a Phase II Trial." Seminars in Oncology 30 (December 2003): 58–62.
Sliva, D. "Ganoderma lucidum (Reishi) in Cancer Treatment." Integrative Cancer Therapies 2 (December 2003): 358–364.
Spetz, A. C., E. L. Zetterlund, E. Varenhorst, and M. Hammar. "Incidence and Management of Hot Flashes in Prostate Cancer." Journal of Supportive Oncology 1 (November-December 2003): 263–273.
Wilson, S. S., and E. D. Crawford. "Prostate Cancer Update." Minerva Urologica e Nefrologica 55 (December 2003): 199–204.
Organizations
The Association for the Cure of Cancer of the Prostate (CaPCure). 1250 Fourth St., Suite 360, Santa Monica, CA 90401. (800) 757-CURE. .
National Cancer Institute. Building 31, Room 10A31 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (800) 4-CANCER. .
National Center for Complementary and Alternative Medicine (NCCAM) Clearinghouse. P. O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226. .
Other
FDA MedWatch Safety Alert for PC-SPES, SPES, updated September 20, 2002. .
National Center for Complementary and Alternative Medicine (NCCAM). Recall of PC-SPES and SPES Dietary Supplements. NCCAM Publication No. D149, September 2002. .
—Lata Cherath, Ph.D.; Michelle Johnson, M.S., J.D.; Rebecca J. Frey, PhD
