The more you know about the normal development and function of the prostate, where it’s located, and what it’s attached to, the better you can understand how prostate cancer develops and impacts a man’s life over time—due either to cancer growth or as a result of treatments.
Normal Anatomy: The normal prostate is a small, squishy gland about the size of a walnut (20 milliliters). It sits under the bladder and in front of the rectum. The urethra—the narrow tube that runs the length of the penis and carries both urine and semen out of the body—runs directly through the prostate. The rectum, or lower end of the bowel, sits just behind the prostate and the bladder. Sitting just above the prostate are the seminal vesicles—two little glands that secrete about 60% of the substances that make up semen. Running alongside and attached to the sides of the prostate are the nerves that control erectile function.
Normal Physiology: The prostate is not essential for life, but it’s important for reproduction. It seems to supply substances that facilitate fertilization and sperm transit and survival. Enzymes like PSA are actually used to loosen up semen to help sperm reach the egg during intercourse. (Sperm is not made in the prostate, but rather the testes.) Other substances made by the seminal vesicles and prostate—such as zinc, citrate, and fructose—give sperm energy to make this journey. Substances like antibodies may protect the urinary tract and sperm from bacteria and other pathogens. The prostate typically grows during adolescence under the control of the male hormone testosterone and its byproduct DHT, or dihydrotestosterone.
Prostate Zones: The prostate is divided into several anatomic regions, or zones. Most prostate cancer develops from the peripheral zone near the rectum. That’s why a digital rectal exam (DRE) is a useful screening test. BPH, a non-cancerous prostate condition, typically develops from the transition zone that surrounds the urethra, or urinary tube. This explains why the condition is typically more symptomatic than prostate cancer.
Treatment-Related Changes: Because the prostate is close to several vital structures, prostate cancer and its treatment strategies can disrupt normal urinary, bowel, and sexual functioning.
- Urinary function—Under normal circumstances, the urinary sphincters (bands of muscle tissue at the base of the bladder and at the base of the prostate) remain tightly shut, preventing urine that’s stored in the bladder from leaking out. During urination, the sphincters are relaxed and the urine flows from the bladder through the urethra and out of the body.During prostatectomy—the surgical removal of the prostate—the bladder is pulled downward and connected to the urethra at the point where the prostate once sat. If the sphincter at the base of the bladder is damaged during this process, or if it’s damaged during radiation therapy, some measure of urinary incontinence or leakage will occur.
- Bowel function—Solid waste that’s filtered out of the body moves slowly down the intestines, and, under normal circumstances, the resultant stool is excreted through the anus following conscious relaxation of the anal sphincter. Damage to the rectum caused by radiation, or more rarely, by surgery, can result in bowel problems, including rectal bleeding, diarrhea, or urgency.
- Sexual function—If the erectile nerves are damaged during prostatectomy, which was standard during this type of surgery up until the mid 1980s, the ability to achieve erection is lost. Sexual desire is not affected, but severing or otherwise damaging the nerves can lead to erectile dysfunction. These nerves can also be damaged by radiation, though this process usually occurs much more slowly over time.
- Modern techniques in surgery (nerve-sparing), radiation (intensity modulated radiation therapy, positioning devices, 3-D conformal technologies), and seed placement (brachytherapy) have been developed to try to minimize these side effects, and this process continues to improve.
- Fertility—About 10% of men with prostate cancer have what is known as seminal vesicle invasion. This means the cancer has either spread into the seminal vesicles or has spread around them. If that occurs, seminal vesicles are typically removed during prostatectomy and targeted during radiation therapy. The loss of the prostate and the seminal vesicles renders men infertile. After surgical removal, ejaculation is dry, but orgasms may still occur.
Prostate Cancer Risk Factors
Prostate cancer is the most common non-skin cancer in America, affecting 1 in 6 men. But who is most at risk of getting prostate cancer and why? There are several major factors that influence risk, some of them unfortunately cannot be changed.
- Age: The older you are, the more likely you are to be diagnosed with prostate cancer. Although only 1 in 10,000 men under age 40 will be diagnosed, the rate shoots up to 1 in 38 for ages 40 to 59, and 1 in 15 for ages 60 to 69. In fact, more than 65% of all prostate cancers are diagnosed in men over the age of 65. The average age at diagnosis of prostate cancer in the United States is 69 years. After that age, the chance of developing prostate cancer becomes more common than any other cancer in men or women.
- Race: African American men are 60% more likely to develop prostate cancer compared with Caucasian men and are nearly 2.5 times as likely to die from the disease. Conversely, Asian men who live in Asia have the lowest risk.
- Family history/genetics: A man with a father or brother who developed prostate cancer is twice as likely to develop the disease. This risk is further increased if the cancer was diagnosed in family members at a younger age (less than 55 years of age) or if it affected three or more family members.
In addition, some genes increase mutational rates while others may predispose a man to infection or viral infections that can lead to prostate cancer.
- Where you live: For men in the U.S., the risk of developing prostate cancer is 17%. For men who live in rural China, it’s 2%. However, when Chinese men move to the western culture, their risk increases substantially. Men who live in cities north of 40 degrees latitude (north of Philadelphia, PA, Columbus, OH, and Provo, UT, for instance) have the highest risk for dying from prostate cancer of any men in the United States. This effect appears to be mediated by inadequate sunlight during three months of the year, which reduces vitamin D levels.
Risk Factors in Aggressive vs. Slow-Growing Cancers
In the past few years, we’ve learned that prostate cancer really is several diseases with different causes. The more aggressive and fatal cancers likely have different underlying causes than slow-growing tumors.
For example, while smoking has not been thought to be a risk factor for low-risk prostate cancer, it may be a risk factor for aggressive prostate cancer. Likewise, lack of vegetables in the diet (especially broccoli-family vegetables) is linked to a higher risk of aggressive prostate cancer, but not to low-risk prostate cancer.
Body mass index, a measure of obesity, is not linked to being diagnosed with prostate cancer overall. In fact, obese men may have a relatively lower PSA levels than non-obese men due to dilution of the PSA in a larger blood volume. However, obese men are more likely to have aggressive disease.
Other risk factors for aggressive prostate cancer include:
- Tall height
- Lack of exercise and a sedentary lifestyle
- High calcium intake
- African-American race
- Family history
Research in the past few years has shown that diet modification might decrease the chances of developing prostate cancer, reduce the likelihood of having a prostate cancer recurrence, or help slow the progression of the disease.
Risk and Other Prostate Conditions
The most common risk misperception is that the presence of non-cancerous conditions of the prostate will increase the risk of prostate cancer. While these conditions can cause symptoms similar to those of prostate cancer and should be evaluated by a physician, there is no evidence to suggest that having either of the following conditions will increase a man’s risk for developing prostate cancer.
- Benign Prostatic Hyperplasia (BPH) is a non-cancerous enlargement of the prostate. Because the urethra (the tube that carries urine from the bladder out of the body) runs directly through the prostate, enlargement of the prostate in BPH squeezes the urethra, making it difficult and often painful for men to urinate.
- Prostatitis, an infection in the prostate, is the most common cause of urinary tract infections in men. Most treatment strategies are designed to relieve the symptoms of prostatitis, which include fever, chills, burning during urination, or difficulty urinating. There have been links between inflammation of the prostate cancer and prostate cancer in several studies. This may be a result of being screened for cancer just by having prostate related symptoms, and currently this is an area of controversy.
More Myths and Non-Risks
Sexual Activity – High levels of sexual activity or frequent ejaculation have been rumored to increase prostate cancer risk. This is untrue. In fact, studies show that men who reported more frequent ejaculations had a lower risk of developing prostate cancer.
- Having a vasectomy was originally thought to increase a man’s risk, but this has since been disproven.
- Medications – Several recent studies have shown a link between aspirin intake and a reduced risk of prostate cancer by 10-15%. This may result from different screening practices, through a reduction of inflammation, or other unknown factors.
- The class of drugs called the statins – known to lower cholesterol – has also recently been linked to a reduced risk of aggressive prostate cancer in some studies.
- It’s worth noting that one recent study did show a nearly twofold risk of developing prostate cancer in men exposed to Agent Orange.
- Alcohol – There is no link between alcohol and prostate cancer risk.
- Vitamin E – Recent studies have not shown a benefit to the consumption of vitamin E or selenium (in the formulations studied) in the prevention of prostate cancer.
The ultimate goal of prostate cancer prevention strategies is to prevent men from developing the disease. Unfortunately, despite significant progress in research over the past 18 years, this goal has not yet been achieved. Both genetic and environmental risk factors for prostate cancer have been identified, but the evidence is not yet strong enough to be helpful to men currently at risk for developing prostate cancer.
By contrast, some success has been seen with strategies that can delay the development and progression of prostate cancer. Studies with finasteride and dutasteride, which are typically used for men with the noncancerous condition BPH, have shown that they can reduce by about 25% the chances that a man will be diagnosed with prostate cancer. The Prostate Cancer Prevention Trial was one of the largest prostate cancer trials ever, and involved over 18,000 men over a decade. This study showed that finasteride was able to reduce the risk of being diagnosed by 25%, but initially found a slightly higher rate of aggressive prostate cancers in men who took finasteride. Later looks at this data have suggested that this may be an artifact or due to a greater ability to find more aggressive cancers due to a smaller gland size (ie a biopsy needle can more easily hit a cancer in a smaller gland than a larger gland). Given that this agent is well tolerated, current recommendations call for a discussion about the risks and benefits of these agents in the prevention of prostate cancer, and of the potential risks and benefits of using these agents for other conditions, such as BPH.
Should I Be Screened?
The question of screening is a personal and complex one. It’s important for each man to talk with his doctor about whether prostate cancer screening is right for him. There is no unanimous opinion in the medical community regarding the benefits of prostate cancer screening. Those who advocate regular screening believe that finding and treating prostate cancer early offers men more treatment options with potentially fewer side effects. Those who recommend against regular screening note that because most prostate cancers grow very slowly, the side effects of treatment would likely outweigh any benefit that might be derived from detecting the cancer at a stage when it is unlikely to cause problems. Recent studies of screening in large U.S. and European populations have suggested that the benefits of screening may not occur for 10 or more years after screening, given the long natural history of prostate cancer. These studies also suggest that many men will need to be screened (over 1,000) and treated (nearly 50) to save one life from prostate cancer. Ultimately, decisions about screening should be individualized based on a man’s level of risk, overall health, and life expectancy, as well as his desire for eventual treatment if he is diagnosed with prostate cancer.
PCF’s thinking aligns closest with The American Urological Association (AUA) Foundation, which has recently changed and updated screening recommendations. AUA recommendations are similar to those of the National Comprehensive Cancer Network (NCCN), but they differ from those of the U.S. Preventive Services Task Force (USPSTF).
You can read all of these recommendations at the following links:
NCCN: http://www.nccn.org/professionals/physician_gls/PDF/prostate_detection.pdf (login required)
When to Start—and Stop—Screening
When to start screening is generally based on individual risk, with age 40 being a reasonable time to start screening for those at highest risk (genetic predispositions or strong family histories of prostate cancer at a young age). For otherwise healthy men at high risk (positive family history or African American men), starting at age 40-45 is reasonable. Guidelines differ for men at average risk. Some recommend an initial PSA and DRE at age 40, and others recommend starting at age 50. In general, all men should create a proactive prostate health plan that is right for them based on their lifestyle and family history. When to stop screening is also controversial. Some groups propose 75 as a reasonable cut-off age. Other groups suggest this is an individual decision based on life expectancy and overall current health. You can find a useful resource for making these decisions at the U.S. Centers for Disease Control and Prevention site.
Screening and Biopsy
A prostate cancer screening may reveal results that prompt a doctor to recommend a biopsy. There are many other supplementary tests and considerations that can help a man who is undergoing screening decide if a biopsy is necessary, including:
– Lower vs. higher free PSA test
- PSA velocity (rate of rise over time)
- PSA density (PSA per volume of prostate)
- Family history
- Prior biopsy findings
- Digital rectal exam results
- Different forms of PSA (i.e. bPSA, pro-PSA)
In general, a lower free PSA (percentage) indicates a higher risk of finding cancer at biopsy, as does a higher PSA velocity and PSA density. Discuss these individual tests with your doctor to make screening decisions that are best for you.
Where Can I Find Free Prostate Cancer Screening?
In the meantime, diet and lifestyle modifications have been shown to reduce the risk of prostate cancer development and progression, and can help men with prostate cancer live longer and better lives.