Prostate Cancer: Causes, Natural History, & Diagnosis
Prostate cancer is the second-leading cause of cancer deaths among men in the United States. Yet, when detected in its early stages, prostate cancer can be effectively treated and cured. What are its causes and symptoms? How is it diagnosed? The following information should help answer such questions.
What is the prostate?
The prostate gland is a small, walnut-sized gland in men. It is located below the bladder and surrounds the upper portion of the urethra. The prostate gland lies in front of the rectum, and its posterior (back) surface can be felt during a rectal examination. The function of the prostate is to secrete fluids that make up part of the semen. The prostate gland may be a source of many health problems in men, the most common being benign prostatic hyperplasia (BPH), prostatitis and cancer.
What is prostate cancer?
Prostate cancer is a significant health-care problem in the United States due to its high incidence. It is the most common non-skin cancer in men affecting over 192,280 American men annually with over 27,000 of these men dying each year. Prostate cancer is different from most cancers in that an appreciable percentage of men, particularly older men with a shorter life expectancy, may have a silent form of this cancer—it will not cause symptoms or progress beyond the prostate gland during their lifetime. Sometimes this cancer can be small, slow growing and present limited risk to the patient. Other times, it can progress rapidly. Clinically important prostate cancers can be defined as those that threaten the well-being or life span of a man.
What are the causes and risks associated with prostate cancer?
What causes prostate cancer is a subject of intensive research. It is likely that prostate cancer occurs due to many reasons. Predominately a disease of elderly men, the diagnosis of prostate cancer is rare before age 40 but increases dramatically thereafter. In the United States, it is estimated that one in 55 men between the ages of 40 and 59 will be diagnosed with prostate cancer. This incidence climbs almost to one in six for men between ages 60 and 79. This association is also reflected in mortality as prostate cancer accounts for about 10 percent of cancer-related deaths in men between the ages of 60 and 79 and nearly 25 percent in those over the age of 80.
Worldwide, prostate cancer ranks third in cancer incidence and sixth in cancer mortality among men. There is, however, a notable variability in incidence and mortality among world regions. The incidence is low (but rapidly increasing in recent years) in Japan and other Asian countries and intermediate in regions of Central America and Western Africa. The incidence is higher in North America and Northern Europe. Although some of these differences may be accounted for by differences in screening for prostate cancer and the risk of other diseases among world regions, it is likely that they can be accounted for, in part, by genetic predisposition as well as diet and other environmental factors.
There are also ethnic determinants of risk. African-Americans are in the highest risk group, with an incidence of more than 200 cases per 100,000 black men. The incidence in Caucasian and Asian men is slightly more than half that of blacks. In addition, African-American men tend to present with more advanced disease and have poorer overall prognosis than Caucasian or Asian men.
Men with a family history of prostate cancer are at an increased risk of developing the disease. The risk correlates with the number of first-degree relatives (father, brother or uncle) affected by prostate cancer and the age at onset. Men with a family history of disease may have a risk of developing prostate cancer 2 to 11 times greater than men without a family history of prostate cancer.
There is also considerable evidence showing that a Western lifestyle is associated with increased prostate cancer risk and increased death from prostate cancer. However, which specific lifestyle factor ? excess calorie intake, excess dietary fat, excess refined sugar intake, reduced fruit and vegetable intake, reduced exercise, or overall higher obesity rates is specifically linked with prostate cancer is not entirely clear. However, it has been clearly shown that obesity is associated with increased risk for death from prostate cancer. Thus, the simplest advice for avoiding death from prostate cancer is to prevent obesity and if you are obese, to lose weight and keep it off.
The most commonly cited dietary risk factor is a high intake of dietary fat, though some more recent studies question whether dietary fat is really linked with prostate cancer. There is a limited amount of evidence to suggest that the worldwide difference in prostate cancer incidence may, in part, be associated with dietary intake of soy proteins. In Asian countries such as Japan and the Republic of Korea where prostate cancer incidence and mortality are just a fraction of that in North America, soy consumption in the form of tofu, soy milk and miso is up to 90 times higher than that consumed in the United States. In a study of more than 40 nations, researchers found soy, on a per calorie basis, to be the most protective dietary factor. This protective role may be associated with two of soy's components, genistein and daidzein that may act as weak estrogens or through other mechanisms. Estrogens are female hormones that inhibit prostate cancer growth. Some experts have suggested that the worldwide differences in prostate cancer incidence may also be explained by the high intake of green tea by residents of Asia. However, teasing out exactly which factors from a complex dietary mix cause prostate cancer is not easy and no clear answers have emerged.
The intake of other certain dietary factors may also reduce the risk of developing prostate cancer. Such substances include lycopene and fish oil. Cooked tomatoes are rich sources of lycopene. Lycopenes are antioxidants that may protect cells from becoming cancerous. Several studies have shown that the likelihood of developing prostate cancer is reduced by high intake of lycopene. Researchers found that men ingesting two or more servings of tomato sauce per week had a 36 percent reduction in cancer risk compared to those who did not, however again, not all studies have supported this. Fish oils (omega-3 fatty acids) are thought to reduce heart disease due to reducing inflammation. Given the presumed importance of inflammation in causing prostate cancer, it stands to reason that fish oils may prevent prostate cancer. Indeed, some studies have suggested this, though others have failed to find any link with prostate cancer risk. Attention has also focused on vitamin D's effect on the prostate. Epidemiologic evidence shows an inverse relationship between prostate cancer risk and ultraviolet radiation, the primary source for vitamin D production. This observation has led some to suggest that higher rates of prostate cancer in the elderly may be partly due to decreased sun exposure or a decline in the body's ability to make vitamin D with aging. However, several recent studies have found no correlation between vitamin D levels and prostate cancer risk and one even found that men with increased vitamin D had a higher risk of aggressive prostate cancer!
The correlation of vasectomy and prostate cancer risk remains controversial. Although some studies have suggested that men who have undergone a vasectomy are at an increased risk of developing prostate cancer, many other studies have failed to show such a correlation.
Finally, a word of caution is needed. Based upon very exciting data, the National Institute of Health embarked a large randomized trial of over 30,000 men to test whether vitamin E or selenium would prevent prostate cancer. Unfortunately, the trial was stopped early because there was no evidence either agent alone or in combination prevented prostate cancer. Moreover, there was a suggestion that men who took vitamin E had an increased risk of prostate cancer and men who took selenium had a slightly higher risk of diabetes! This highlights the point that there is no easy substitute for a healthy lifestyle involving eating a balanced diet, avoiding dietary excesses, eating plenty of fruits and vegetables, getting lots of exercise, and most importantly achieving and maintaining a normal body weight.
What are the symptoms of prostate cancer?
In its early stages, prostate cancer often causes no symptoms. When symptoms do occur, they may include any of the following: dull pain in the lower pelvic area; frequent urination; problems with urination such as the inability, pain, burning, weakened urine flow; blood in the urine or semen; painful ejaculation; general pain in the lower back, hips or upper thighs; loss of appetite and/or weight; and persistent bone pain.
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How is prostate cancer diagnosed?
Currently, digital rectal examination (DRE) and prostate specific antigen (PSA) are used for prostate cancer detection. The age at which screening for prostate cancer should begin is not known with certainty.
DRE: The DRE is performed with the man either bending over, lying on his side or with his knees drawn up to his chest on the examining table. The physician inserts a gloved finger into the rectum and examines the prostate gland, noting any abnormalities in size, contour or consistency. DRE is inexpensive, easy to perform and allows the physician to note other abnormalities such as blood in the stool or rectal masses, which may allow for the early detection of rectal or colon cancer. However, DRE is not the most effective way to detect an early cancer, so it should be combined with a PSA test.
PSA Test: The PSA test is usually performed in addition to DRE and increases the likelihood of prostate cancer detection. The test measures the level of PSA, a substance produced only by the prostate, in the bloodstream.
This blood test can be performed in a clinical laboratory, hospital or physician's office and requires no special preparation on the part of the patient. Ideally, the test should be taken before a DRE is performed or any catheterization or instrumentation of the urinary tract. Furthermore, because ejaculation can transiently elevate the PSA level for 24 to 48 hours, the patient should abstain from sexual activity for two days prior to having a PSA test. A tourniquet or rubber strap is tied around the upper arm to mildly restrict the flow of blood and keep blood in the vein. Then, a needle with a tube-like container attached is inserted into a vein, usually in the bend of the elbow or the top of the hand. After a sufficient sample of blood is obtained, the needle is withdrawn, a bandage is placed on the puncture site and firm pressure is held until the bleeding stops. The entire test takes less than five minutes and produces only mild discomfort. After, the patient may experience slight bruising at the puncture site.
Very little PSA escapes from a healthy prostate into the bloodstream, but certain prostatic conditions can cause larger amounts of PSA to leak into the blood. One possible cause of a high PSA level is benign (non-cancerous) enlargement of the prostate, otherwise known as BPH. Inflammation of the prostate, called prostatitis, is another common cause of PSA elevation, as is recent ejaculation. Prostate cancer is the most serious possible cause of an elevated PSA level. The frequency of PSA testing remains a matter of some debate.
Currently, it is recommended that both a DRE and PSA test be used for the early detection of prostate cancer. It is important to realize that in most cases an abnormality in either test is not due to cancer but to benign conditions, the most common being BPH or prostatitis.
Biopsy: Prostate biopsy is best performed under transrectal ultrasound guidance using a spring-loaded biopsy device coupled to the transrectal probe. The patient is prepared with an enema and an antibiotic. The lubricated ultrasound probe is inserted into the rectum. Some lubricating gels include a topical anesthetic. Patients are positioned on their side for this procedure. The physician will first image the prostate using ultrasound noting the prostate glands size and shape and whether or not any other abnormalities exist, the most common of which are shadows which might signify the presence of prostate cancer. However, not all prostate cancers are visible. After the prostate gland has been anesthetized with an injection of a local anesthetic through a long fine needle that is passed through the probe, the physician performs the biopsy. Using the spring-loaded biopsy device attached to the ultrasound probe, the physician performs multiple biopsies of the prostate gland. Generally, 10 to 12 (or more, depending upon the size of the prostate gland and the prior PSA and biopsy history of the patient) biopsies will be performed. Each biopsy removes a cylinder of prostate tissue approximately 3/4 inch in length and 1/16 inch in width. The entire procedure takes 20 to 30 minutes. The biopsy tissue taken will then be examined by a pathologist (a physician who specializes in examining human tissue to determine whether it is normal or diseased). The pathologist will be able to confirm if cancer is present in the biopsy tissue. If cancer is present, the pathologist will also be able to grade the tumor. The grade indicates the tumor's degree of aggressiveness—how quickly it is likely to grow and spread. The Gleason grading system is the most widely used system. In this system, because often several different tumor patterns are seen, the most common tumor pattern is assigned a score from 1 to 5 and the second most common pattern is similarly assigned a score, using the same scale. The two scores are added together to give a Gleason sum ranging between 2 and 10. Scores of 2 to 6 designate mildly aggressive, 7 moderately aggressive and scores of 8 to 10 highly aggressive.
The transrectal ultrasound guided prostate biopsy is usually well tolerated. Injecting local anesthetics into the area before biopsy may minimize this discomfort. Blood in the ejaculate (hematospermia) and blood in the urine (hematuria) occur in most patients, but resolves within a few days for the urine and a few weeks for the semen. High fever is rare, occurring in only 1 to 2 percent of patients. The antibiotic is continued for at least 48 hours after the biopsy procedure.
How is prostate cancer staged?
Once prostate cancer has been diagnosed by a prostate biopsy, the physician must stage the disease to determine the extent of the cancer (i.e., the "T" stage) and whether it has spread beyond the prostate gland to the surrounding tissues, the seminal vesicles, the lymph nodes and/or the bones. The T stage is determined by the DRE and other imaging studies of the prostate gland and surrounding tissues, such as the ultrasound scan, CT scan, MRI scan, or MR spectroscopy scan. The T stage is divided into the following categories:
T1: Doctor is unable to feel the tumor
T1a: Cancer is found incidentally during a transurethral resection (TURP) for benign prostatic enlargement. Cancer is present in less than 5% of the tissue removed and is low grade (Gleason < 6).
T1b: Cancer is found after TURP but is present in more than 5% of the tissue removed or is of a higher grade (Gleason > 6)
T1c: Cancer is found by needle biopsy that was done because of an elevated PSA
T2: Doctor can feel the tumor when a digital rectal exam (DRE) is performed but the tumor still appears to be confined to the prostate
T2a: Cancer is found in one half or less of only one side (left or right) of the prostate
T2b: Cancer is found in more than half of only one side (left or right) of the prostate
T2c: Cancer is found in both sides of the prostate
T3: Cancer has begun to spread outside the prostate and may involve the seminal vesicles
T3a: Cancer extends outside the prostate but not to the seminal vesicles
T3b: Cancer has spread to the seminal vesicles
T4: Cancer has spread to adjacent organs, such as the urethral sphincter, rectum, bladder, and/or wall of the pelvis
To determine if the cancer has spread to the lymph nodes or bones, the physician may order a CT or MRI scan of the pelvis. A bone scan may be obtained to rule out metastases to the bone. Sometimes follow-up imaging studies are needed to further evaluate abnormalities found on the bone scan. These tests are not recommended for men with a Gleason grade <7 and a PSA level <10 ng/ml as they rarely show disease.
Prostate cancer represents a spectrum of disease. Although some cancers may grow so slowly that treatment may not be needed, others grow fast and are a threat to life. Determining the need for treatment can be a complex decision. Initially, the need for treatment should be based on the stage and grade of the cancer as well as the age and health of the patient. Many physicians have sought to devise risk assessment schemes that predict the likelihood of disease recurrence if patients are treated and progression or significant growth of their cancer if they undergo initial surveillance or watchful waiting. By combining many types of information (i.e., serum PSA level, clinical stage, Gleason score, extent of cancer in biopsy specimens), patients can be advised of the likely aggressiveness of their cancer and the need for and types of treatment available. However, the longer the patient's life expectancy, the more uncertain the prediction becomes, as most prostate cancers progress with time. Imaging tests, such as a radionuclide bone scan, CT scan or MRI, and MR spectroscopy may help assess whether the cancer is still confined to the prostate or has spread elsewhere. When prostate cancer spreads (metastasizes) it is usually progresses, though not always in such a neat step-wise fashion, first by perforating the capsule and extending into the periprostatic tissues, then to the seminal vesicles, then to the lymph nodes and finally to the bones, lungs, and other organs. Not all men with prostate cancer need to undergo imaging tests as the risk of spread to other organs can be estimated on the basis of serum PSA levels and cancer grade. It is the standard of care to omit the bone scan in patients with newly diagnosed, untreated prostate cancer, who have no symptoms from their cancer, a Gleason score < 7 and have serum PSA concentrations less than 10 ng/ml and certainly in those with serum PSA concentrations less than 15 ng/ml (unless the Gleason score is 7 or higher) . Similarly, a pelvic CT scan or MRI may not be necessary in men with lower grade cancers, cancers still confined to the prostate and serum PSA values less than 10 ng/ml.
Frequently asked questions:
Can prostate cancer be prevented?
There is controversy about true prevention. Some physicians believe that anti-androgen drugs, such as finasteride and dutasteride, can prevent prostate cancer. However, others are skeptical, and some believe that anti-androgens can only slow the progression of well-differentiated elements but may allow higher-grade elements to emerge as the dominant elements in the tumor. In randomized trials, men taking these drugs are less likely to be diagnosed with prostate cancer, though their impact of cancer aggressiveness and whether this will translate into a lower risk of death from prostate cancer is not known. Some physicians believe that general health measures might reduce the risk of prostate cancer, such as eating achieving and maintaining a normal body weight, a healthy diet, being physically active and visiting the doctor on a regular basis. As clinical studies, which found that supplements such as vitamin E and selenium do not prevent prostate cancer, point out—there is no current short-cut that can replace a healthy lifestyle.
What is the outlook for prostate cancer?
The number of men diagnosed with prostate cancer remains high. However, 5-year relative survival rates have increased dramatically and there has been at least a 25% reduction in the age-specific prostate cancer mortality rate since the beginning of the PSA era. It is estimated that 99 percent of men diagnosed with localized or regional prostate cancer survive at least five years, while only 33% of those with metastases at diagnosis survive 5 years.
The Urology Care Foundation has teamed up with the National Football League to fight prostate cancer! For more information and resources, visit www.KnowYourStats.org.
Reviewed: January 2011
Last updated: March 2013
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