Prostate cancer is the most common non-cutaneous cancer of men in the United States with almost 200,000 new cases diagnosed each year and accounting for over 40,000 deaths per year. It is the second most common cause of cancer deaths in the United States. The lifetime risk of developing prostate cancer is approximately 1 in 8. Although the exact causes are not known, there do exist some known risk factors for developing prostate cancer. These include the following:
1. Age: Prevalence of prostate cancer increases in a near exponential rate with age approximately 95% of cancers diagnosed in men between the ages of 45 and 89.
2. Family history: The incidence of prostate cancers increased in male relatives of prostate cancer patients. Although most patients have no family history (about 10%) are in higher risk. Persons who have one "close degree" relative (for example a brother or a father) have a two-fold increased risk. If a person has two "close degree" relatives, he has a 5-fold increase risk of developing prostate cancer.
3. Other possible risk factors include: high-fat diet, living in western countries (Western Europe, Scandinavian countries, and the United States), hormonal imbalances, and perhaps certain other dietary considerations such as vitamins (Vitamin A, Vitamin D). At the present, these are only speculated risk factors. Precise interactions are not clearly understood. This area however, is under intense investigation by researchers in attempts to more clearly define the risk factors, and therefore the causes of prostate cancer.
Prostate cancer begins when normal gland cells within the prostate turn into malignant or cancerous cells. As stated above, the exact mechanism of this transformation is not known and is the focus of much research performed today. A localized cluster of tumor cells can be used to grow and divide initially within the prostate itself. Cells will eventually spread beyond the outside of the prostate gland in to adjacent organs (such as the seminal vesicles) and into the surrounding fatty tissue. Spread to nearby lymph nodes will occur. In advanced stages, the cancer will spread to other organs - most commonly the bones, although prostate cancer is a relatively slow-growing cancer.
In the early stages of prostate cancer, (that is confined to the prostate), symptoms are generally silent. In fact, some of the mild urinary symptoms that patients may experience typically come from concomitant/unrelated BPH and are not attributable to the cancer that may also exist. Again, it should be emphasized that in early stages of prostate cancer, tehre are typically no symptoms. When the cancer becomes more extensively involved to the prostate, urinary symptoms may then develop (but less than 10% of patients have symptoms). The lack of any symptoms in prostate cancer emphasizes the important role of screening measures in all patients regardless of symptoms. In most patients with prostate cancer (especially localized prostate cancer) patients will usually have no symptoms. The most common symptoms of prostate cancer do occur ni advanced disease, particularly when it involves the bones. Persistent and often severe pain in the back, hips or other bones is characteristic.
The initial detection of prostate cancer is made by the digital rectal examination, and/or by PSA testing. DRE and PSA are the most useful first-line tests in evaluating/screening patients for prostate cancer. The DRE consists of a rectal examination palpation of the prostate to feel for any prostate nodules, firmness, or otehr abnormalities. All men with abnormal prostate examinations regardless of PSA levels should undergo a subsequent prostate biopsy to rule out prostate cancer. PSA is a routine blood test for screening of prostate cancer. It is not a substitute for the digital rectal exam, but used to compliment/supplement in screening. As a single test, it is the most sensitive measure for the detection of prostate cancer. The most effective overall methods of early detection are the combined use of the digital rectal exam and the PSA. The American Urological Association recommends the yearly PSA tests for all men over the age of 50. Yearly digital rectal exams are recommended for all men over the age of 40. In patients with a strong family history of prostate cancer and an African-American patient's screening measures by PSA are recommended to begin at 10 years earlier at age 40.
If an abnormality is detected on digital rectal exam, or PSA, prostate needle biopsy should be performed. This is performed generally in an urologist's office under ultrasound guidance. In order to adequately sample all the areas of the prostate, 6 to 10 biopsies and sometimes more are performed at that setting. It is an uncomfortable procedure, but usually well tolerated with low risks of side effects (primarily bleeding and infection). Biopsy samples are then reviewed by a pathologist and examined for the presence or absence of prostate cancer, as well as the grade and extent of the cancer if it does exist.
When the diagnosis of prostate cancer is made, patients are generally assigned a grade and stage of cancer (and this is generally true for all cancer types). Grades refer to how aggressive cancer cells appear under the microscope. Low-grade cancers (score 1 to 3) or high-grade cancers (score 4 to 5). Often the Pathologist will provide two scores and a resulting sum will be obtained. Low-grade cancers will typically have a sum of 2 to 6, moderate cancers a sum of 7, and high-grade cancers have a sum of 8 to 10. The stage of cancer reflects where (location) the cancer is. Cancers confined to the prostate include stage T1 (PSA-detected) or T2 cancers (a nodule palpated on rectal exam). Both stage T1 and T2 cancers are also termed "clinically localized". Stage T3 and T4 cancers are felt to extend outside the prostate into adjacent structures. N+ refers to the presence of positive lymph nodes (that is the cancer involving some of the surrounding pelvic or retroperitoneal lymph nodes), and M+ refers to spread to other organs (especially bones).
- Stage A = no nodule on exam; typically PSA detected - Stage 1
- Stage B = nodule confined to prostate on exam = Stage 2
- Stage C = spread outside prostate to adjacent structures = Stage T3, T4
- Stage D1 = spread to lymph nodes = Stage N+
- Stage D2 = spread to bones or other organs = Stage M+
Treatment is dependent on the stage, grade, patient age, and health status and patient preference. Treatments for localized cancer (stage T1, T2) include surgery (radical prostatecomy), radiation therapy (either external beam radiation or brachytherapy or seeds), or perhaps in certain cases, no therapy at all (watchful waiting). Patients with more advanced disease are typically treated with hormonal therapy. Again, the precise treatment strategy should be individualized for each patent after counseling with his urologist.
Surgical removal of the prostate gland is termed a radical prostatectomy. This involves removal of the gland itself and the tissue surrounding the prostate.
It can be performed through a lower abdominal incision (radical retropubic prostatectomy) or through the perineum (radical perineal prostatectomy).
Radical prostatecomy provides the highest rate of cure from this cancer. As an overall treatment strategy, it is perhaps best for patients that are under age 70 (with localized cancer) and with a greater than 10 year life expectancy. Side effects of treatmetn include impotency (although the nerve connections can occasionally be spared, help to limit impotency and incontinence (a 5 to 20% risk). More experimental surgical includes cryosurgery, although long-term results of this treatment are not clear. Recurrences do occur and side effects are common.
External Beam Radiation
There exists a lengthy experience, good long-term results with external beam radiation therapy. Radiation therapy typically involves a 7-week course including treatment 5 days a week for seven weeks. Side effects may include bladder irritation, rectal irritation, importence and incontinence.
Brachytherapy involves the placement of permanent radioactive seed implants into the prostate. It is typically an outpatient procedure, but performed under general anesthesia. Brachytherapy appears to be as effective as external beam radiation therapy for low grade, low stage cancers, but some studies have suggested that it is less effective for higher grade and higher stage cancers. The long-term results of brachytherapy, especially significant long-term results over ten years are not well known at this time.
Prostate therapy is dependent on the male hormone testosterone to grow. Therefore, by depleting the testosterone levels in patients, the prostate cancer can be put into remission. This is not considered a curative therapy, because after approximately 2 to 5 years (and this is highly variable) the cancer begins to grow without the necessity of testosterone, that is the cancer becomes "hormone insensitive, hormone independent". Ways of depleting the testosterone level include surgical orchiectomy (removal of the testicles), or also can be performed via medications, which deplete the body's testosterone levels (LHRH agonists, anti-androgens).
This is essentially no therapy at all, but close surveillance. It is typically reserved for older patients (greater than 70 years old), those with poor health status, or perhaps those with lower grade, lower stage cancers and who are asymptomatic. Occasionally used for younger, healthier patients with low-grade, low-stage cancers, and only a small amount of cancers detected on biopsy. Close monitoring of the rectal exam and significant PSA changes needs to be performed, and any significant changes do warrant the intervention. It is not recommended for younger patients with long life expectancies, patients with high-grade cancers or patients with high-stage cancers. Future directions involve primarily the prevention of the cancer itself. This mainly being in the form of dietary modification (for example limitaton of dietary fat, vitamins, soy products, etc), medical or chemoprevention, vaccines, and perhaps some molecular and gene therapies.
The overall incidence of prostate cancer is declining thanks to public awareness, early diagnosis and treatment. As in decades past, the majority of patients would present with metastatic disease. Today, the vast majority of patients with newly detected prostate cancer, present with clinically localized cancer that is minimal to treat and possible to cure. Clearly much work needs to be done regarding scientific investigation of prostate cancer, particularly in prevention, less invasive, more aggressive therapies.
- UNC Lineberger Comprehensive Cancer Center
- Prostate Cancer Foundation
- Dr. Patrick Walsh's Guide to Surviving Prostate Cancer
- American Cancer Society
- National Cancer Institute
- Cancer Net