Studies show that PSA screening saves lives for people with prostate cancer, because it finds cancer early when it is most treatable. [1] Prostate cancer is the second leading cause of cancer deaths in men after lung cancer. [3] So, you would think all men should get PSA testing throughout their lives to screen for prostate cancer. Unfortunately, it is not that simple. [1-4]

What’s a Normal PSA?

The main problem with PSA is that it is not a very reliable test. There is no settled normal range that can tell if you have prostate cancer. [2] You can have a normal PSA and still have prostate cancer, and you can have an abnormal PSA and not have prostate cancer. In fact, most men with a high PSA don’t have prostate cancer. [1]

A PSA level goes up with prostate cancer but it also goes up with age. PSA can go up with two very common prostate conditions, benign prostatic hyperplasia (BPH) and inflammation of the prostate (prostatitis). [1-3] PSA can even go up after having sex or riding a bicycle. [2]

PSA is measured in nanograms per millimeter (ng/mL). Although most doctors would consider a PSA of less than 4 ng/mL normal, some doctors say anything over 2.5 is abnormal. This is what the studies say:

• About 15 percent of men with a PSA under 4 have prostate cancer.
• About 25 percent of men with a PSA between 4 and 10 have prostate cancer.
• About 50 percent of men with a PSA over 10 have prostate cancer. [2]

The Problem With Prostate Cancer Screening

The only way to diagnose prostate cancer is with a prostate biopsy. You would think it would be worthwhile to do PSA screening for all men and a prostate biopsy on every man with an abnormal PSA, but that is not the case. [1-4] Prostate biopsy has risks. It can cause bleeding, pain, urinary retention, and a urinary tract or prostate infection. [4] Since most men with a high PSA do not have prostate cancer, these risks are important to consider. [1-4]

There is also a problem with prostate cancer itself. Even if a biopsy shows prostate cancer, many men with prostate cancer will never have any serious problems from their cancer. They will die from something else. For these men, the treatment can be worse than the disease. Treatment can cause serious urinary and sexual problems. [1-4]

Because most men with a high PSA do not have prostate cancer and many men with prostate cancer do not need treatment, guidelines for PSA screening rely heavily on a discussion of the risks and benefits with your doctor. [1-5]

PSA Screening Recommendations

Different medical organizations have slightly different guidelines. These are the guidelines for PSA screening from the  American Urological Association, the specialists who diagnose and treat prostate cancer:

• PSA is not needed under age 40.
• PSA is not needed for men ages 40 to 54 unless they are at higher risk for prostate cancer. Being African American or having a family history of prostate cancer puts you at higher risk.
• PSA should be considered for men ages 55 to 69 after discussing the risks and benefits of the test and of prostate cancer treatment.
• PSA is not recommended for men age 70 or older. [5]

What Happens After a PSA Test? 

If you and your doctor decide to do a screening test and the test is normal, you may not need to think about another test for a few years. If the test is abnormal, you and your doctor will discuss the risks and benefits of further testing:

• You may have another screening test before or after your PSA called a digital rectal exam (DRE). During DRE, your doctor places a gloved finger into your anus to feel your prostate. If your prostate feels enlarged or abnormal, your doctor may recommend further testing or a biopsy.
• Further testing could include another PSA test or a more specialized PSA blood test that may tell your doctor more about your prostate cancer risk. There are many options including tests called prostate health index, PSA velocity, PSA density, free PSA and others.
• Further testing may include an imaging study (MRI or trans rectal ultrasound)) of your prostate. [2]
• Your doctor will consider any further testing, your PSA test, and your DRE, along with your age, overall health and your risk factors. You and your doctor should use this information to weigh the risks and benefits of a prostate biopsy. [1-4]

The bottom line on PSA as a screening test for prostate cancer is that it is still a valuable test when used along with your DRE, other tests, and your personal risk factors to help you and your doctor decide if you would benefit from a prostate biopsy. [1-5]

Other Uses for Prostate Specific Antigen Testing

Outside of prostate cancer screening, there are other uses for PSA testing. If you have had a biopsy that shows a slow growing prostate cancer, your doctor may advise watchful waiting. In this case, PSA testing may be done periodically to see if your cancer becomes more active. Any increase in PSA could be considered abnormal. If you have been treated for prostate cancer, periodic PSA testing may be done to see if there are any signs of cancer coming back. Any increase would be abnormal. [3]

If you have symptoms of prostate cancer, PSA testing may be done to find out if you have prostate cancer. When you already have symptoms, PSA is no longer considered a screening test. It is a diagnostic test. [3] Let your doctor know if you have any of these prostate cancer symptoms:

• Problems passing urine, like slow flow, increased frequency, or loss of control
• Blood in your semen or urine
• Trouble getting or keeping an erection
• Weakness or numbness in your legs or feet
• Bone pain in your hips, back, or ribs [6]

RECOMMENDED FOR YOU

• How to Avoid Prostate Cancer
• 12 Risk Factors for Prostate Cancer
• Beyond the PSA Test: Options for Screening
• It Isn’t Time to Abandon the Prostate-Specific Antigen Test Just Yet
• PSA Lab Test Results: These 10 Factors Can Affect Your Numbers 
• An Abnormal PSA Result: What Comes Next?
• Are You Keeping Tabs on Your PSA Levels?

SOURCES

1. Memorial Sloan Kettering Cancer Center, Prostate Cancer Screening
2. American Cancer Society, Screening Tests for Prostate Cancer
3. American Society for Clinical Chemistry, Lab Tests Online, Prostate Specific Antigen (PSA)
4. CDC, Prostate Cancer, What Are the Benefits and Harms of Screening? 
5. American Urological Association, Early Detection of Prostate Cancer (2018)
6. American Cancer Society, Signs and Symptoms of Prostate Cancer

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Your doctor may elect to biopsy your prostate based on whether or not you have possible symptoms of prostate cancer, on your PSA levels, and/or on your digital rectal exam (DRE) findings.

There are differing opinions among professional medical organizations about whether performing a biopsy based on abnormal PSA results alone is appropriate. A number of other tests (e.g., PCA3 and PSA velocity) have been developed as screening tools in an effort to either avoid unnecessary biopsy or improve prostate gland cancer detection. Most experts agree, however, that there isn’t enough evidence yet to make them part of a routine screening process. You and your healthcare provider should discuss these options prior to a biopsy.

If prostate cancer is suspected, your doctor will perform a biopsy guided by transrectal ultrasound. A small ultrasound probe is inserted into the rectum to guide the biopsy needle to the biopsy locations. The needle is inserted through the wall of the rectum into the prostate gland to retrieve small pieces of tissue. Typically, at least 12 samples of tissue are taken from different areas of the prostate. This can be done on an outpatient basis and is usually a brief procedure.

The tissue samples are sent to a pathology lab for examination. If cancer cells are evident, they typically are graded using a system called the Gleason score, an indicator of how likely the cancer is to spread. Tissue from two different parts of the prostate gland are examined and given a score from 1 to 5; the numbers from each part are then added together to create the Gleason score. A lower score suggests a lower likelihood of spreading, while a higher score suggests a greater chance.

Once a diagnosis of prostate cancer has been made, additional tests will be performed to determine whether or not the cancer has spread beyond the prostate. These test results, along with the Gleason score, will be used to assign the disease a prostate cancer stage. The system most often used is the American Joint Committee on Cancer “TNM” system, which provides a Roman numeral staging score from I-IV based on the size of the primary Tumor, whether or not there is lymph Node involvement, whether the tumor has Metastasized, the PSA level at diagnosis, and the Gleason score.

First line of defense in detecting prostate cancer is the digital rectal exam (DRE), plus a measurement for prostate specific antigen (PSA) in the blood. These steps are controversial, however, because some contend PSA has led to over-diagnosis and debilitating over treatment for cancers that aren’t lethal.

The more advanced the cancer, the higher the TNM stage number. For example, in stage I prostate cancer, the cancer has not spread beyond the prostate itself while in stage IV prostate cancer, the cancer has spread beyond the prostate, either to nearby organs and/or lymph nodes or to more distant sites in the body.

Tests performed to help stage the cancer may include:

• Computed Tomography (CT): CT scans are used to look for evidence of metastasis, particularly to lymph nodes.
• Magnetic Resonance Imaging (MRI): MRI is also used to look for evidence of metastasis.
• Bone Scan: Since bone is one of the most common places for prostate cancer to metastasize, bone scans are often used to look for disease spread.
• Positron Emission Tomography (PET): PET scans can also be used to look for evidence of metastasis. They are particularly helpful in looking for evidence of disease recurrence in men who have been previously treated for prostate cancer.
• Lymph Node Biopsy: Knowing whether or not your prostate cancer has spread to lymph nodes is an important part of determining what treatment regimen you should receive. Imaging tests such as CT scans can help provide information as to whether or not the lymph nodes are involved, but biopsying lymph nodes is the only way to definitively make this determination. If your doctor doesn’t anticipate surgery as a part of the treatment regimen, he may opt to biopsy your lymph nodes laparoscopically. In other situations, your surgeon may biopsy your lymph nodes during an operation to remove your prostate gland.

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In these asymptomatic men, prostate cancer is often detected during routine screening with tests such as a digital rectal exam, urinalysis, and possibly a prostate specific antigen (PSA) test by their healthcare professional. This is particularly true of men with early stage prostate cancer, but may also be true of men with more advanced cancer.

Other men with prostate cancer may experience symptoms ranging from mild to severe that may mimic symptoms of other prostate conditions, including benign prostatic hyperplasia/BPH (non-cancerous enlargement of the prostate gland) and prostatitis (inflammation of the prostate).

Some of these prostate cancer symptoms are more common than others and tend to occur in more localized prostate cancer (cancer limited to the prostate gland or adjacent tissues) while others are more likely to occur in men whose prostate cancer has spread or metastasized to other parts of the body. If you experience any of these symptoms, you should consult your healthcare provider immediately.

Common Prostate Cancer Symptoms

• Urinary frequency: Men with prostate cancer may feel the need to urinate more often, particularly at night.
• Urinary retention: Prostate cancer may cause the sensation of not being able to empty your bladder completely.
• Weak urinary stream: Some men with prostate cancer may feel that their urinary stream is diminished or that they dribble urine.
• Difficulty initiating urination: It may be difficult to begin urinating in some men suffering from prostate cancer.
• Painful urination: Urinating may cause pain or discomfort (dysuria) in some cases of prostate cancer.
• Blood in the urine: Prostate cancer can result in blood in the urine (hematuria) in some men.
• Painful ejaculation: Some men suffering from prostate cancer experience pain with ejaculation.

Other Prostate Cancer Symptoms

Some prostate cancer symptoms are less common and in some men may be associated with more advanced disease.

• Bowel problems: Because the prostate lies just in front of the rectum, prostate cancer that has caused significant enlargement of the prostate or that has spread into nearby tissues including the rectum, may cause intestinal problems such as constipation or diarrhea.
• Erectile dysfunction: Some men may experience impotence if the prostate cancer has affected nerves involved in an erection.
• Blood in the semen: The prostate gland secretes fluid that is part of semen. Cancer in the prostate may cause irritation and inflammation, leading to blood in the semen.
• Lymphedema: If the prostate cancer blocks flow of lymphatic fluid in lymph nodes or lymphatic vessels, men may experience swelling of the pelvic region or legs.
• Bone pain: When prostate cancer spreads, one of the tissues in the body that it often spreads to is bone. Pain in the back, hips, legs, or feet may result if the cancer has spread to bones of those regions.
• Unexplained bone fracture: Metastatic bone disease may result in fractures that occur with only very mild accidents or trauma that would normally not precipitate a break in bones.
• Numbness in the lower extremities: Prostate cancer that has metastasized to the spine may cause compression of nerves resulting in numbness or tingling of the hips, legs, or feet.
• Fatigue: Men with early stage prostate cancer may experience fatigue, but significant fatigue is more likely to occur with cancer that has spread.

If you experience any of these prostate cancer symptoms, you should consult your healthcare provider immediately. There are many tests and procedures available for prostate cancer diagnosis and many options for prostate cancer treatment.

Originally published in February 2016 and updated.

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While most men do not die from prostate cancer, it is the second leading cause of cancer-related death. Data from the National Cancer Institute estimates that 14 percent of American men will be diagnosed with prostate cancer during their lifetime. So, what is prostrate cancer?

There are two changes that can occur in the cells of the prostate that some research suggests might be precursors to prostate cancer. One of these is called high-grade prostatic intraepithelial neoplasia (PIN) in which the cells look abnormal but are not yet cancerous.

Twenty percent of men with high-grade PIN have cancer in another part of the prostate. Low-grade PIN is seen in half of all men by the age of 50 and does not necessitate any more aggressive monitoring. Proliferative inflammatory atrophy (PIA) is a condition in which the prostate cells are smaller than usual and have signs of inflammation. There is some evidence that having PIA might increase your risk of high-grade PIN or prostate cancer.

While researchers do not yet know exactly what causes prostate cancer, they have identified a number of risk factors for development of the prostate disease.

Risk Factors for Prostate Cancer

First line of defense in detecting prostate cancer is the digital rectal exam (DRE), plus a measurement for prostate specific antigen (PSA) in the blood. These steps are controversial, however, because some contend PSA has led to over-diagnosis and debilitating over-treatment for cancers that aren’t lethal.

There are a number of identified risk factors for prostate cancer, including:

• Family history: Having a first degree relative (father or brother) who has had prostate cancer increases your risk of the disease.
• Age: The risk of prostate cancer rises with increasing age.
• Race: African-American men have a higher risk of developing prostate cancer and dying from prostate cancer than men of other races.
• Obesity: Research has demonstrated an association between obesity and prostate cancer. Obese men appear to have an increased risk of developing aggressive prostate cancer and of dying from prostate cancer.
• Smoking: A history of smoking has been linked to an increased risk of aggressive prostate cancer in some studies. The relationship between smoking and prostate cancer risk appears to be dose-dependent such that men who smoke the most have the highest risk of developing aggressive prostate cancer.
• Diet: Some research has suggested that a diet rich in red meat or high-fat dairy products increases the risk of prostate cancer. Studies have also shown that men who took folate supplements and men who took vitamin E supplements alone have an increased risk of prostate cancer.
• Sleep disorders: There is some evidence that men who suffer from sleep disorders have an increased risk of developing prostate cancer. One study demonstrated this risk to be between 1.6 and 2.1 times greater and that the risk increased with the severity of sleep impairment.

If prostate cancer is suspected, your doctor will likely order a PSA test, which, along with a digital rectal exam, will help clarify your prostate cancer symptoms. But an elevated PSA result only means the process of dealing with your condition has just begun. If this initial screening goes beyond normal PSA levels, additional tools up to and including biopsy will be under consideration.

Originally published in March 2016 and updated.

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Still, prostate cancer was responsible for an estimated 31,620 deaths in 2019, according to the American Cancer Society. The risk of prostate cancer increases dramatically with age. Six out of 10 cases are in men over 65, and the average age at diagnosis is 66. Prostate cancer is rare in younger men, but when it does occur, it tends to be more aggressive.

Screening for prostate cancer is controversial. In most men diagnosed with prostate cancer, the disease is slow growing and not life threatening. For these men, diagnosis may lead to unnecessary tests and treatments, not to mention the stress of living under the shadow of a cancer diagnosis. It’s like going for a walk in the woods: Even if there are hundreds of snakes and spiders lurking near the path, the chances are that they will leave you alone. But once someone tells you there are hundreds of snakes and spiders lurking by the path, you begin to get anxious and panicky. The risk is the same, but now you know about it!

Pathology

The prostate is particularly susceptible to gene mutations. Some 95 percent of prostate cancers begin in the semen-­producing glandular cells and are classed as adenocarcinomas. Four percent arise in the prostatic urethra’s transitional cells—the lining of the urethra as it passes through the prostate. In fact, changes begin there with cellular gene mutations years before cancer is detected.

Over time, fast-growing mutations may develop, forming clusters of abnormal cells, tumors, and eventually cancer. Less than 1 percent are squamous cell carcinomas (normally seen on skin), most often occurring after radiation or hormone treatment. Seventy percent arise in the peripheral zone, 15 to 20 percent in the central zone, and 10 to 15 percent in the transitional zone. At biopsy, the majority of cancers are found to be affecting multiple areas of the prostate.

Local Spread

As clusters of cancer cells enlarge, they begin to invade adjacent areas. Tumors arising in the transitional zone spread to the nearby bladder neck. Those arising in the peripheral zone creep into the ejaculatory ducts and seminal vesicles. Later in the process, they may reach, and breach, the sheath of connective tissue around the gland, called the prostatic capsule.

Distant Spread (Metastasis)

Sometimes prostatic cancers spread far beyond the prostate, forming distant cancers or metastases (plural of metastasis). The most common sites for prostatic metastases are in the bones, lungs, liver, and adrenal glands.

Measuring Severity

The severity of prostate cancer is measured using two metrics:

• Grading. The Gleason score defines types of cells, and the level of abnormality (histology).
• Staging. The Tumor-Node-Metastasis (TNM) classification describes how widespread the cancer is.

At diagnosis, most prostate cancers have low levels of abnormal cell changes and remain confined to the prostate. These cancers tend to be slow growing and have good outcomes. The cancers with the worst outcomes tend to have significant cell abnormalities and have spread beyond the capsule of the prostate.

Prostate Cancer Symptoms

Clinical presentation data provide a picture of prostate cancer symptoms:

• 47 percent present with no symptoms; cancer is detected during screening.
• 38 percent present with increased urinary frequency, especially at night.
• 23 percent present with a decreased urine stream.
• 10 percent present with urinary urgency.
• 1 percent present with blood in urine (hematuria) or semen.

Prostate cancer that has spread may present with:

• Reduced appetite and unexplained weight loss
• Bone pain, with or without pathologic fracture
• Feet or ankle pain and swelling
• Kidney failure.

Causes and Risk Factors

The cause of prostate cancer is complex and not fully understood. We do know that the glandular tissue of the prostate is prone to genetic mutations that may be triggered by a variety of factors. In many men, the disease seems to be random, and the cause remains unknown.

The term “risk factors” refers to attributes or exposures in an individual that increase the odds of getting the disease. For prostate cancer, there are many risk factors. Let’s consider the common ones.

Age. The most significant risk factor for developing prostate cancer is one that can’t be helped: aging. Sixty percent of all prostate cancers are diagnosed in men over age 65.

Genetic Factors. Genetics are at play in the 5 to 10 percent of prostate cancer patients who have a strong family history. A man with a first-degree relative (brother or father) with prostate cancer has double the risk of developing the disease and presents six to seven years earlier than other men.

The National Cancer Institute explains that the following factors are suggestive of genetic risk:

• Multiple first-degree relatives with prostate cancer, including three successive generations with prostate cancer on the mother’s or father’s side.
• A relative with early-onset prostate cancer (age ≤55 years).
• Family history of prostate cancer and other cancers (e.g., pancreatic, breast).

Researchers have so far discovered more than 100 gene variations or mutations associated with prostate cancer. Certain clusters of gene variations are helpful for predicting risk and outcome, and some mutations are linked to more aggressive cancers.

Notable culprits are the BRCA1 and BRCA2 mutations, also linked to breast cancer risk in women. Normally, these genes produce proteins that help to suppress cancer. Research suggests that men with BRCA2 mutations who develop prostate cancer are more likely to develop aggressive disease, with advanced staging at diagnosis, higher rates of metastasis, and poorer survival rates. A recent study found that African-­American men with prostate cancer are more likely to have the BRCA1 and BRCA2 genes, a possible explanation for why this group has poorer outcomes.

Herein lies a common dilemma in medicine: What do we do when someone is identified with a genetic risk? There is a danger that this knowledge may cause unnecessary panic and needless tests and treatments. While prostate cancer is very common, most patients do not die from it. But genetic testing—when used prudently—can help identify men with aggressive cancers earlier and potentially save lives. Genetic testing is also increasingly used for targeting treatment.

Epigenetics. Fortunately, men with prostate cancer risk genes are not destined to develop cancer. The field of epigenetics is showing that lifestyle and environmental factors can alter the inheritance and expression of genes. This suggests that improving lifestyles and environment may reduce the risk of prostate cancer, along with the risk of many other chronic illnesses.

Racial Factors. Data from the Centers for Disease Control and Prevention and the National Cancer Institute show that there are racial differences in the incidence of prostate cancer. In one study, African-American men were found to have the highest rates of prostate cancer, followed by white, Hispanic, American Indian/Alaska Native (AI/AN), and Asian/Pacific Islander (A/PI) men.

Research suggests that African-American men may be at greater risk, in part, because of genetic factors and hormonal differences. However, diet, income, education, and health-care access may also play a role. African-American men also tend to get prostate cancer earlier and in a more aggressive form than other races, with death rates being significantly higher.

On the plus side, recent research suggests that when African-American men diagnosed with early stage prostate cancer receive equal access to health-care and the most effective treatments, their risk of death is the same as that of Caucasian men.

Lifestyle Factors. One of the likely causes of prostate cancer is inflammation, and there is an established link to lifestyle. The typical Western lifestyle, characterized by sedentary habits and poor diet, is a major cause of inflammation in the body and a significant risk factor for many chronic diseases, including cancer, heart disease, and diabetes.

According to Cancer.org, “Internationally, the incidence of prostate cancer varies by more than 50-fold, with the highest rates being in North America, Australia, and northern and central Europe, and the lowest rates being in southeastern and south-central Asia and northern Africa.”

The human body is a highly complex, interconnected system. No organ exists in isolation, so what is good for health in general is likely good for the prostate. The body has a remarkable ability to heal itself and maintain a healthy equilibrium, but sometimes our actions push it to the limit, and disease is the result.

There is substantial research linking lifestyle to prostate cancer risk. But due to the complex nature of disease and of lifestyle, it can be difficult to prove that one particular factor causes or prevents a specific disease. For example, men who are obese have an increased risk of prostate cancer, but is this because of the excess body weight itself or because they have a poorer diet and are less likely to exercise? Likewise, men who are strict vegans have a lower risk of prostate cancer, but is this because they eat no animal products or because they are more likely to be non-smokers and lead active lifestyles?

Diet and Nutrition. The links between diet, general health, disease prevention, and longevity are increasingly compelling. Large longitudinal studies—where subjects are followed for years (such as the Framingham Heart Study and the Nurses’ Health Study)—provide strong evidence.

One example of a healthy diet is the Mediterranean diet, which is high in fruits and vegetables, nuts, grains, olive oil, and lean sources of protein and low in factory-produced, processed foods. A comprehensive review of research, published in the journal Nutrients, showed that strict adherence to the Mediterranean diet only slightly lowered the risk of death from prostate cancer, but had a significant effect on the risk of some other cancers (like gastric, liver, pancreatic, and lung cancer).

Diet is also important to health and well being after cancer diagnosis. A study in Cancer Prevention Research compared two basic eating patterns in men who had been diagnosed with non-metastatic prostate cancer. One was a typical Western diet, relatively high in processed and red meats, high-fat dairy, and refined grains. The other was a “prudent” pattern relatively high in fruits, vegetables, fish, legumes, and whole grains. The study found that men with a Western dietary pattern were at greater risk of death from prostate cancer or any cause, compared with those who ate the prudent diet.

Obesity and Metabolic Syndrome. Obesity has been linked to a higher risk of prostate cancer. A recent study in BMC Medicine found that men with a higher body mass index (BMI) and waist circumference (indicators of obesity) had an increased risk of high-risk tumors and were more likely to die of prostate cancer. A possible mechanism for the increased risk of prostate cancer in overweight men is thought to lie with insulin levels. Insulin is a growth factor, so when high, it promotes cell division in abnormal cells.

Metabolic syndrome is a group of risk factors including obesity, high blood pressure, cholesterol abnormalities, high triglycerides, and insulin resistance. It is thought to be a precursor for cardiovascular disease and type 2 diabetes. Research published in 2017 in the International Journal of Cancer suggests that metabolic syndrome is associated with increased risk of fatal prostate cancer.

Other Factors

Also linked to prostate cancer are dietary supplements, heart disease, exercise, and smoking, among other factors.

Dietary Supplements. Many men take dietary supplements to improve health, and assume that supplements cause no harm. But troubling research suggests this is not so. Several studies have linked supplements to increased risk of prostate cancer:

• The Selenium and Vitamin E Cancer Prevention Trial (SELECT) reported that men who took 400 International Units (IU) of vitamin E but no other supplements had a 17 percent higher risk of prostate cancer.
• Zinc: A study from Boston University concluded “long-term zinc intake from multivitamins or single supplements was associated with a doubling in risk of prostate cancer.”
• Folic Acid: University of Southern California researchers found that men who took a 1-milligram daily supplement of folic acid had twice the risk of prostate cancer compared with men who took a placebo.
• Vitamin D: There is conflicting evidence as to whether vitamin D supplements decrease or increase the risk of prostate cancer. However, a 2018 review of 19 studies found that men with higher blood levels of vitamin D also were at greater risk of prostate cancer.

While these studies are not conclusive, they do suggest that if you want to reduce your prostate cancer risk, it may be safer to obtain your nutrients from a healthy diet rather than by taking vitamin supplements.

Heart Disease. Heart disease is the most common cause of death in men. When two diseases are very common, it’s hard to tease out whether one causes the other. Heart disease and prostate cancer share similar risk factors—including poor diet, obesity, smoking, and inactivity—but we cannot say with certainty that heart disease causes prostate cancer (or vice versa).

Smoking. There is no doubt that smoking is bad for health. It increases the risk of major chronic illnesses, like heart disease and lung cancer. At this time, the research that smoking specifically causes prostate cancer is mixed, though preliminary evidence suggests a relationship. A study combining data from 24 studies found that the heaviest smokers had a 24 to 30 percent greater risk of death from prostate cancer, compared with nonsmokers. Another large review, published in 2018, found that men who were smokers at the time of treatment for localized prostate cancer were at greater risk that their cancer would come back and prove fatal.

Alcohol Consumption. Excessive alcohol consumption is bad for you, contributing to heart disease and stroke and other significant health problems. The relationship between drinking and prostate cancer is less clear, although preliminary research suggests a connection. A 2018 study in Cancer Prevention Research found evidence that “heavier alcohol intake earlier in life and higher cumulative lifetime intake were positively associated with high-grade prostate cancer diagnosis, while current intake was unrelated to prostate cancer.” This suggests that alcohol consumption alone may not cause prostate cancer, but if you do develop the disease, the prognosis might be poorer if you are a heavy drinker.

Exercise. While there is solid evidence that regular exercise is good for general health, there is limited evidence of an impact on prostate cancer risk. However, one Harvard study reported that men who engaged in three hours a week of vigorous exercise were 61 percent less likely to die from prostate cancer than men who did less than one hour a week.

Testosterone Levels. In men with prostate cancer, male hormones—testosterone and other androgens—are known to fuel the growth of the cancer. But does testosterone cause prostate cancer? Males castrated before puberty and those with androgen insensitivity syndromes do not develop prostate cancer. Beyond these extreme cases, the relationship between testosterone levels and prostate cancer risk remains unclear.

Some studies have found a possible link between high levels of circulating testosterone and greater risk of prostate cancer, and that lower testosterone is associated with decreased risk. Other studies have not found such connections, and scientists continue to study this important question.

Another related issue is whether testosterone replacement therapy (TRT) poses a cancer risk. TRT is the standard medical treatment for hypogonadism, in which the body doesn’t produce enough testosterone. TRT is also used illegally in bodybuilding and performance enhancement. Medical treatment is not thought to increase the risk of prostate cancer, because it is correcting naturally low testosterone. The jury is out on the risks for men taking testosterone without prescription.

Ejaculation Frequency. Research in the journal European Urology suggests that frequent ejaculation may lower the risk of prostate cancer. The study followed nearly 32,000 men from 1992 to 2010, who periodically filled out health questionnaires. Men who reported 21 or more ejaculations per month were about 20 percent less likely to develop prostate cancer compared to men who reported four to seven monthly ejaculations. It’s unclear why frequent ejaculations would reduce cancer risk. Some speculate that it prevents cancer-causing substances from building up in the prostate.

Vasectomy. Some research found a greater risk of prostate cancer in men who have vasectomies. Half a million American men have a vasectomy each year, so it’s a potentially important risk factor. The American Urological Association reviewed the research on the link and concluded that, based on the results of two meta-analyses, vasectomy is not associated with prostate cancer. A 2017 review in JAMA Internal Medicine confirmed that vasectomy had an insignificant impact on aggressive prostate cancer risk.

Prevention

The development of prostate cancer is complicated, and it is unlikely it can be prevented altogether. However, large observational studies hold out much hope that even though you can’t change your age, your race, or your family history, you still may be able to reduce your overall risk by living a healthy lifestyle. And that also helps prevent heart disease and other important male health problems.

A Closer Look at Lifestyle

If you want to take control of your health and potentially reduce your risk of prostate cancer, here are some strategies that may help.

Improve Your Diet. Eat more fruits and vegetables, eat lean protein, and reduce intake of red meat cooked at high temperatures (processed, grilled, fried, or broiled).

• Eat a wide variety of fruits and vegetables of different colors so you get plenty of micronutrients. Include tomatoes (high in carotenoids) and cruciferous vegetables (such as broccoli and cauliflower).
• Eat antioxidant-rich foods like blueberries, watermelon, and arugula; these may reduce DNA damage.
• Food allergies and insensitivities are increasingly common: Listen to your body and avoid foods that make you feel unwell, even if they are on the “healthy” list.
• Limit full-fat dairy intake.
• Moderate amounts of tea and coffee may be beneficial for prostate health.
• Consider eating more soy, but make sure it’s organic.
• Replace your saturated fat intake with healthier unsaturated fats from sources such as avocados or olives. Eat oily fish like salmon two to three times a week.

Exercise Regularly. This will improve your overall health and may reduce your prostate cancer risk. Research suggests that even if you start exercising in middle or later life, it’s still beneficial for lowering disease risk.

Drugs and Medications. Some research suggests that certain medications may reduce the risk of prostate cancer:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin, ibuprofen (Advil, Motrin), and naproxen (Aleve, Anaprox).
• Metformin (Glucophage, Glumetza, Fortamet, Riomet), used to treat type 2 diabetes.
• Statins, used to lower bad LDL cholesterol, such as atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), pitavastatin (Livalo), pravastatin (Pravachol), rosuvastatin (Crestor), and simvastatin (Zocor).
• A class of medications called 5-alpha reductase inhibitors—used to help shrink non-cancerous enlarged prostates—can reduce the risk of prostate cancer by about one-fourth. However, they may increase the risk of more aggressive cancers. If you are at high risk, you may wish to discuss the use of these drugs as a preventative measure with your clinician. Commonly prescribed types include dutasteride (Avodart) and finasteride (Proscar).

Diagnosing Prostate Cancer

There are two stages to the diagnostic evaluation for prostate cancer:

• Screening: defined as the testing of individuals with no symptoms in an attempt to catch early disease.
• Investigations: assessments and tests done in individuals with symptoms or where screening has identified a potential problem.

Let’s begin by talking about the PSA test that’s both a screening and diagnostic test.

What Is PSA?

Prostate-specific antigen (PSA) is a blood test commonly used in two scenarios:

• A screening test (men with no symptoms)
• A diagnostic test (men with symptoms)

PSA is a protein made by the prostate to maintain semen’s liquid form, allowing sperm to move freely from the male to the female reproductive system during natural conception. Small quantities of PSA make their way into the bloodstream, allowing for measurement in the PSA blood test. Blood levels of PSA are often elevated in men with prostate cancer, making it a way to pick up cancer early—before clear signs and symptoms become apparent.

Over a billion PSA tests have been done since it was approved by the FDA in 1986 (to monitor treatment response and disease recurrence) and in 1994 (as a screening and diagnostic test).

The PSA test, when used for cancer screening, is controversial because it can lead to unnecessary tests and treatments, but it is also extremely useful as a diagnostic test that has saved millions of lives by picking up aggressive cancers so that men can receive early treatment.

Understanding the PSA Test. The PSA test measures tiny quantities of PSA in the blood. The scale used is nanograms (one-billionth of a gram) per milliliter (one-thousandth of a liter) (ng/ml). A PSA test result under 4 ng/ml traditionally has been considered “normal.” There is, however, a caveat: Some aggressive cancers have a PSA in this range. The Prostate Cancer Prevention Trial (PCPT) warns there is no PSA level at which the prostate cancer risk is zero. For the general male population, a PSA level between 4.1 and 10 carries a 47 percent risk of prostate cancer. PSA over 10 carries a 58 percent risk of prostate cancer, and thereafter the risk is closely correlated to PSA level.

Advanced PSA Measurements. Researchers have not given up on the PSA test as a prostate-cancer screening tool and are continually working to refine and improve it.

Screening

Screening for asymptomatic men (showing no symptoms) for prostate cancer involves the PSA test and sometimes a digital rectal examination (DRE). Routine prostate cancer screening is controversial for two main reasons:

• The risks of screening healthy men may outweigh the potential benefits.
• Prostate cancer is often not life threatening. In fact, in many cases prostate cancers are so slow-growing that they can almost be considered benign.

The goal of prostate cancer screening, therefore, is to detect high-risk tumors while they are treatable and potentially curable.

Digital Rectal Examination (DRE)

This simple test is performed during a physical examination. You lie on your side and the doctor inserts a lubricated, gloved finger (digit) into the rectum. The prostate lies in front of the rectum, so the doctor can feel (palpate) it through the rectal wall. This provides a way to assess the gland’s size and texture, whether it contains lumps, and whether pressing on it causes pain.

While the DRE can be embarrassing and a little uncomfortable, it is a useful screening test and is over in a couple of minutes.

Like the much-maligned PSA test, it is a crude and unreliable test, but doctors believe it is still worth doing in the absence of more definitive screening. It can also detect problems with other organs in the pelvic region, including the bladder and bowel.

To Screen or Not to Screen?

Screening tests are those done on people who feel well, with the aim of detecting serious disease before symptoms arise and before the disease is advanced, thus allowing early treatment and improving outcomes.

All screening tests have their pros and cons. Even a simple test like routine blood pressure monitoring can have a downside: Sometimes blood pressure is elevated due to anxiety about visiting the doctor (white coat syndrome) and testing may cause unwarranted alarm and further unnecessary testing. It’s important to weigh the advantages and disadvantages of any screening test before you make a decision.

Pros and Cons of PSA Screening

As is the case with most cancers, the earlier prostate cancer is detected, the greater the odds of a cure. Proponents argue that screening is the only way to catch prostate cancer at an early stage. They also point to the fact that death rates from prostate cancer have decreased significantly since widespread screening began in the early 1990s.

The great news is that screening has dramatically increased the detection of prostate cancer while it is still localized to the prostate, a significant factor in improved outcomes.

It is now rare for men to be first diagnosed with prostate cancer when it is advanced. Deaths from prostate cancer have significantly declined in the last 20 years, which is great news by any standard.

The Disadvantages of PSA Screening

The extent to which PSA has been responsible for the decline in deaths is controversial. While the drop in deaths from prostate cancer is cause for celebration, opponents of PSA testing suggest that it’s probably because of improved treatments, not PSA screening. They note that the survival rate was already improving in the United States, and survival rates have improved in countries that do not screen.

The case against screening points to these potential problems:

False Negatives. The PSA test misses some cancers. Around 20 percent of men confirmed to have prostate cancer have normal PSA levels (less than 4 ng/ml). False negatives give a false sense of security.

Other Causes of Low PSA. Unfortunately, there are factors that naturally reduce PSA levels, further complicating the interpretation of results. These include:

• Cigarette smoking (past or present).
• Obesity. Greater blood volumes may dilute PSA.

Medications

• BPH treatments. 5-alpha reductase inhibitors like finasteride (Proscar) and dutasteride (Avodart), although they may improve the PSA test’s accuracy.
• Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen (Advil, Motrin).
• Diuretics for high blood pressure. Examples include chlorothiazide (Diuril) and hydrochlorothiazide (Microzide, Dyazide, Maxzide).
• Statins for high cholesterol, such as atorvastatin (Lipitor) and simva­statin (Zocor).

False Positives. Some 70 to 80 percent of men with elevated PSA levels do not have cancer. For these men, a positive test leads to a cascade of testing that often results in the man being told he doesn’t have cancer. That would be fine—if testing caused no harm. However, being told that you have a positive result may cause severe psychological distress for weeks or months.

And when a PSA test result raises suspicions of prostate cancer, the next test is prostate biopsy, which may cause complications such as infection, blood in the semen and/or urine, urinary symptoms, and, possibly, erectile dysfunction. (See page 23 for more about prostate biopsies.)

Other Causes of High PSA. Unfortunately, there are factors that naturally increase PSA levels, further complicating the interpretation of results. These include:

• Prostatitis (non-cancerous inflammation), benign prostatic hypertrophy, and urine infections.
• Tests or surgery on the prostate, including DRE
• Recent ejaculation, especially in older men
• Exercise, most notably bicycle riding (doctors advise not to ride a bicycle for 24 hours before PSA testing)
• Hepatitis
• Bypass surgery

The Unpredictability of Positives. Statistically speaking, a very high PSA level is closely correlated to aggressive prostate cancer. But, when PSA is mildly elevated, the results are less clear-cut. Some men with high PSA turn out to have no cancer or a very slow-growing type, while some men with a low level of PSA turn out to have aggressive cancer.

For example, a study in the New England Journal of Medicine found that 15 percent of men with relatively low PSA levels (less than 4 ng/ml) who had biopsies turned out to have prostate cancer. And 15 percent of those cases were aggressive cancers based on standard tumor staging.

The bottom line is that there appears to be no “safe zone” in PSA testing. A low PSA level indicates potentially lower risk, but doesn’t completely rule out cancer.

Number Needed to Treat. Statistics have measured the number of patients who need to be treated to prevent one extra bad outcome. In 2012, the European Randomized Study of Screening for Prostate Cancer trial showed that “to prevent one prostate cancer death, 935 men would need to be screened and 37 cancers would need to be detected.” Some researchers considered this rate to be unacceptably high.

PSA Screening: The Research

Two major studies have fueled the debates about prostate cancer screening.

PLCO Trial. The National Cancer Institute sponsored the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial in the United States. They followed 77,500 men, all of them between ages 55 and 74, who had no history of prostate, lung, or colorectal cancer. Men were randomized into one of two groups:

• The intervention arm received trial screening, chest x-rays, flexible sigmoidoscopy, PSA blood tests, and digital rectal exams.
• The control arm received standard care.

Enrollment began in 1993, participants were screened through 2006, and data were collected through 2015. Researchers reported that seven to 13 years later, “There was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening, which forms part of usual care, and there was no apparent interaction with age, baseline comorbidity, or pretrial PSA testing.”

In other words, the very costly screening program statistically had little effect on outcomes. However, the study has been heavily criticized for several flaws, paramount of which is the fact that 52 percent of the control group was in fact screened at some stage.

European Randomized Study of Screening for Prostate Cancer. The ERSPC, which involved eight European countries, is the largest-ever prostate cancer screening study. A total of 182,000 men (162,000 of them between ages 55 and 69) were randomized into the intervention and control groups. Those in the intervention arm were offered PSA blood tests every two or four years. Those with a PSA level of more than 3.0 ng/ml were offered biopsy. Patient follow-up was extended to 11 years and is ongoing.

In recent analysis, the researchers concluded that “a man who undergoes PSA testing will have his risk of dying from prostate cancer reduced by 29 percent.”

The major downside, as they discovered, was that there were high rates of false positives: 30 percent of those with detected cancers did not have progressive disease. The “number needed to treat” (NNT, or number treated to avoid one death) was 48, which is considered to be high.

Professor Fritz Schroeder, the study coordinator, concluded “screening programs for prostate cancer will not be feasible until the medical communities can confidently balance the risk of reducing death from prostate cancer with these unacceptably high levels of overdiagnosis and overtreatment.”

See screening guidelines on page 21.

Diagnostic Investigations

If you have prostatic symptoms or a high PSA or abnormal DRE results, your doctor will take you through some or all of the following steps.

• Full medical history, including symptoms, surgeries, medications, and family history.
• Full physical examination of all body systems, including a DRE.
• Symptom assessment, such as the AUA Symptom Score.
• Urine test to look for infection, blood, and glucose.
• Blood test for:
  • General health markers (blood count and chemistry).
  • PSA, advanced PSA testing (free PSA, PSA velocity, Prostate Health Index, 4Kscore, or prostate cancer antigen 3.
• Transrectal ultrasound (scans via the rectum, using a probe) to look for abnormalities or lesions.

Transrectal Ultrasound (TRUS) Biopsy. During a TRUS-guided biopsy, an ultrasound probe is inserted into the rectum and a spring-loaded needle takes multiple tiny samples (core needle biopsy). These samples are sent to the laboratory to look for cancerous cells. Performed under local anesthetic in the urologist’s office, the biopsy takes about 15 minutes and is mildly uncomfortable. Sometimes, a biopsy fails to detect cancer when there is a high level of suspicion, so a repeat biopsy may be needed.

Potential complications of a biopsy include bleeding, lower urinary tract symptoms, urinary tract infection, and prostate infection (prostatitis). Some men report worsening of erectile dysfunction. The risk of infection can be reduced by giving prophylactic antibiotics before the biopsy. Men should avoid taking nonsteroidal anti-inflammatory drugs (like aspirin or ibuprofen) and fish oils for three days prior to biopsy, to reduce bleeding risk.

Image-guided targeted fusion biopsy is one of several techniques being used to improve accuracy of biopsy. First the patient undergoes an MRI, during which abnormal areas are flagged. Then an ultrasound-guided biopsy takes samples from these targeted areas.

Post-Diagnosis Investigations

If you have a confirmed diagnosis of prostate cancer, your doctor may want to perform further tests to determine the severity and to check whether it has spread (metastasized). Prostate cancer can be tiny when it first presents, and its spread is unpredictable, so these tests are very useful.

Investigations may include:

• Pelvic ultrasound to look for local spread beyond the prostate.
• Bone scan to look for bone metastases.
• Chest x-ray to look for lung and chest wall metastases.
• Advanced imaging such as CT scans (computed tomography), MRIs (magnetic resonance imaging), and PET scans (positron emission tomography)—which may be used to look for signs of spreading to the lymph nodes, pelvis, or beyond.
• Lymph node biopsy to look for spread to lymph nodes
• Genomic testing to help determine which cancers are benign and low-risk, and which are aggressive and life threatening. Examples include Oncotype DX Genomic Prostate Score (GPS), ProMark, Decipher, and Prolaris.

The results of these tests can be used to guide decisions regarding treatment.

Biopsy Results: Histology

Biopsy samples are evaluated for changes in cells. Changes are seen on the following continuum.

High-Grade Prostatic Intraepithelial Neoplasia (HGPIN or PIN). As with other cancers, prostate cancer starts with precancerous changes that may be discovered via biopsy. PIN is divided into low-grade (mild dysplasia) and high-grade prostatic intraepithelial neoplasia (HGPIN, or severe dysplasia). HGPIN are abnormal cells that have not become invasive and are found in 80 to 100 percent of prostates with carcinoma. This finding suggests that they are a precursor to carcinoma in some men. It should be noted, however, that these cells are detected in up to a quarter of men, most of whom do not go on to develop cancer. In those who do develop carcinoma, PIN predates malignancy by 10 or more years. A small body of evidence suggests that when PIN is found in multiple sites, there is an increased risk of prostate cancer. If PIN is detected, a six-month follow-up biopsy may be recommended.

Atypical Small Acinar Proliferations (Atypia or ASAP). Atypia is a more significant finding than PIN, as approximately 50 percent predate cancer. It is found at biopsy in 2 to 5 percent of men. In atypia, there are abnormal cells; however, they are few in number, and they don’t quite look like cancer cells. Plus other features (such as inflammation) may confuse the picture. Some clinicians describe atypia as “suspicious” or “highly suspicious for cancer” and recommend rebiopsy in six months, with more extensive sampling.

Cancer. If cancer cells are found at biopsy, they will be “graded” to see how abnormal they are. Low-grade cancers most resemble normal tissue and may have only just begun to invade locally. The clinician will also look for evidence of spread beyond the prostate gland.

Measuring Cancer Severity

Clinicians use three main criteria to determine the severity of cancer:

• Blood tests. May include PSA levels, advanced PSA tests, and biomarkers.
• Grading. The Gleason score, which defines types of cells (histology).
• Staging. TNM Classification (tumor node metastasis), which defines where cancer is found.

The Gleason Score. This is the most commonly used grading score for prostate cancer. First developed in 1966, the Gleason score has been refined several times since then. It is based purely on the “architecture” or histology of the cells—that is, how they look in the laboratory. It has been found to be a good indicator of how cancer will progress and, thus, is a useful guide for treatment.

The Gleason score is composed of two scores—one for each of the two most common types of cancer cells found in the biopsy samples. Both types are graded using a scale of 1 to 5. A score of 1 means the cells are very close to normal; a score of 5 means the cells are very abnormal. The scores are added to get a final score between 2 and 10. In practice, prostate cancers are graded as Gleason scores 6 (low risk) through 10 (high risk).

Modified Gleason Score. Some clinicians are shifting over to the new International Society of Urological Pathology (ISUP) score. It ranks cancers from 1 to 5, corresponding to Gleason grade 6 to 10:

• Gleason scores ≤ 6: ISUP grade 1 (low risk, least aggressive)
• Gleason score 3 + 4 = 7: ISUP grade 2 (intermediate risk, favorable)
• Gleason score 4 + 3 = 7: ISUP grade 3 (intermediate risk, unfavorable)
• Gleason score 8: ISUP grade 4 (high risk, most aggressive)
• Gleason score 9 to 10: ISUP grade 5 (high risk, most aggressive)

ISUP’s proponents say that the scale is potentially less confusing to patients because it ranks low-risk cancers as grade 1 instead of grade 6 (as in the conventional Gleason score). Research is ongoing to establish whether using the ISUP grading scheme leads to better overall outcomes, such as fewer cases of over-treating low-risk cancers and being able to identify the most high-risk, potentially aggressive cancers.

Staging Prostate Cancer. TNM Classification was developed by the American Joint Committee on Cancer (AJCC). The tumor node metastasis, or TNM, staging system is used to define prostate cancer progression. It has three components: primary tumor (T), lymph node (N) involvement, and metastasis (M: spread to other organs). See ‘Prostate Cancer Stages’ for a summary of these stages.

Risk Group. Having completed the necessary investigations, your doctor will determine your risk group. This, in turn, will help predict prognosis and guide treatment.

The search for new, more reliable assessments is ongoing.

Enhanced Screening: New Developments

Genetic mutations are occurring all the time in our bodies, but most result in no harm to the individual and the mutation line dies out. When mutations occur in certain genes, disease—including cancer—may follow.

Somatic Mutations. The most common type of mutation involves genes responsible for cell growth, cell repair, and cell division. These so-called somatic mutations can lead to abnormal or uncontrollable cell division, with the result being a tumor.

Somatic mutations are not passed down to future generations. Most prostate cancers are due to these sporadic somatic mutations and are therefore not hereditary or detectable on genetic screening.

Germline Mutations. Less common are “germline mutations” that affect every cell in the body. They are usually triggered by lifestyle and environmental factors and changes in other genes. Germline mutations can be inherited.

Inherited genes implicated in prostate cancer include BRCA1, BRCA2, and HOXB13. BRCA1 and BRCA2 repair damaged DNA and suppress tumors, keeping cell division at a normal level.

Gene Fusion. Gene fusion is a hybrid gene formed from two previously separate genes. The fusion occurs due to DNA damage, when damaged pieces of DNA merge with other fragments of DNA, creating new genes.

Generalized inflammation and environmental factors have been implicated in this process. (The study of gene alteration due to environment, as discussed earlier, is known as epigenetics.)

In as many as 50 percent of men with prostate cancer, there is gene fusion of TMPRSS2 and ERG. TMPRSS2 is a gene that makes an enzyme called transmembrane protease serine 2. ERG is a gene responsible for transcribing DNA for the cancer-causing gene ETS (erythroblast transformation-specific).

Other genetic markers implicated in prostate cancer include: TP53, AR, PTEN, PIK3CA, RB1, APC, CHD1, MYC, and ATM.

The aim of current research is to identify more genes involved in prostate cancer, understand the mode of action, and develop therapies to reduce the burden of disease.

Liquid Biopsies. Liquid biopsies take a urine or blood sample and look for evidence of cancer cells, DNA, or fragments of cancer. They can be used to help detect early cancer, develop a treatment plan, and track progress of treatment. The advantage is that liquid biopsies are far less invasive than repeated prostate biopsies.

For example, the ExoDx Prostate IntelliScore measures exosome (fragments of cells) biomarkers in urine. The Stockholm3 (STHLM3) blood test screens several forms of PSA, other protein biomarkers, and germline genetic markers and clinical variables. One study found that use of the STHLM3 could reduce the number of biopsies by nearly one-third and the number of benign biopsies by 44 percent, according to the researchers.

IsoPSA is another blood test that’s showing promise. A 2017 study reported in European Urology concluded that “IsoPSA demonstrated a 48 percent reduction in false-positive biopsies… [and a] 45 percent reduction in the false-positive rate.”

Still another potential new screening technique is surface-enhanced Raman scattering (SERS). In preliminary research, SERS has shown promise for distinguishing between high- and low-risk prostate cancer based on blood or urine samples.

Prostate Cancer Treatment

It’s normal to feel shocked and overwhelmed by a diagnosis of prostate cancer. But unlike many other cancers, most prostate cancers are slow growing and not life-threatening. The five-year survival rate for local or regional prostate cancer (confined to the prostate and nearby tissues and organs) is virtually 100 percent. But if, at diagnosis, the prostate cancer has spread to more distant parts of the body (i.e., metastatic prostate cancer), the five-year survival rate is around 30 percent.

If you receive a prostate cancer diagnosis, listen carefully to the information your clinical team gives you and take your time to process it. If you’re uncertain about something, ask for clarification either at the time or at a later date. Get as much information as you can in writing, so that you can learn more when the initial shock has died down.

Myriad treatment options exist for prostate cancer. There is no one-size-fits-all approach. Deciding on the best treatment protocol is a complicated process. Prostate cancer treatments involve complex trade-offs, and each treatment has its own risks and benefits.

The big dilemma in prostate cancer is whether to treat it in “low-risk” cases. Some slow-growing cancers pose little immediate risk to health, and there are significant complications to treatment.

The aim of treatment should be to improve longevity and quality of life. A younger man—one who potentially has decades of life ahead of him—may decide that living with cancer and the uncertainty it brings will warrant aggressive treatment with a high chance of a cure. An older man who has other health problems may decide to hold off on treatment until his doctor tells him it’s urgent.

Shared Decision-Making

The American Urological Association (AUA) offers useful guidelines for doctors on how to treat prostate cancer. They recommend beginning with an initial assessment, followed by counseling and then shared discussion regarding treatment options. These options are geared around the following factors:

Risk Category. At diagnosis, cancers are often referred to as low-, intermediate-, or high-risk. Doctors determine the risk according to the characteristics of the tumor, its aggressiveness, and its spread, as assessed via these procedures:

• Blood tests (PSA levels, advanced PSA tests, and biomarkers)
• Grading the types of cancer cells (Gleason score)
• Staging the spread of the cancer (TNM classification)

Life Expectancy. Determined by current age and general health. This may be overwhelming to discuss, but it’s important. As you have learned, many prostate cancers are so slow-growing that they may take decades before they are problematic.

Current Level of Functioning and Lifestyle. It’s important to assess your baseline quality of life, including work, family, love life, leisure time, and so on.

Expected Post-Treatment Function. Consider expectations surrounding your sex life. It’s important to look ahead, too. What would you like your life to look like in five or 10 years?

Your Values and Preferences. Consider the importance of issues like recovery time, side effects, and distance you’re willing to travel for treatment.

Your Clinician’s Preference and Expertise. Many of the treatments discussed later in this chapter are not offered by every doctor. Outcomes are better when the doctor is an expert in a particular technique. As a general rule, look for an experienced surgeon who is completing at least 40 radical prostatectomies each year, as they tend to have better outcomes, with lower complication rates.

Lifestyle. Your clinical team should also talk to you about your modifiable risk factors—smoking, obesity, and diet, for example. Lifestyle changes may have an impact on your risk of cancer progression and also may improve your quality of life, general health, and wellbeing.

Specialists. You may also be referred to a range of specialists (like medical oncologists, radiologists, and surgeons) who can advise you on the various treatment options. You may also be informed of your eligibility to take part in ongoing clinical trials for new therapies.

Research with care. We live in an age when access to medical information is at our fingertips 24/7. It’s great to research and become an expert on your own condition, as then you can make informed decisions and advocate for yourself. There is a down side, however, to personal research. First, you may become frightened or obsessed while reading information that isn’t designed for the public. Plus, there’s a lot of inaccurate information on the internet, and with it comes the potential to make bad decisions. That said, there are some excellent sites that are reliable, among them the National Comprehensive Cancer Network, Cancer.org and Cancer.gov. You may also want to access professionally run community groups and support groups. Also, be extremely wary of getting advice from friends and family: They are biased, don’t understand your clinical picture, and may feed you dubious advice. Your health is too precious to leave to anyone who isn’t a medical professional.

AUA Treatment Guidelines

The American Urological Association (AUA) has published guidelines for treating localized (i.e., nonmetastatic) prostate cancer. Highlights of the recommendations for low-, intermediate-, and high-risk prostate cancer are as follows:

Very-Low/Low-Risk Prostate Cancer

• Active surveillance. Preferred approach for men with very low-risk (localized) prostate cancer and most men with low-risk prostate cancer. Active surveillance refers to deferring treatment until follow-up tests indicate that the cancer is starting to present a greater risk. The intention is still to cure.
• Watchful waiting: May be an option for older men with low-risk cancer whose life expectancy is less than five years. Watchful waiting, or observation, means deferring treatment until symptoms appear or change. It is sometimes confused with active surveillance, in which the intention is to cure, not just relieve symptoms.
• Radical prostatectomy or radiation therapy: For those at higher risk of progression, including younger men with strong family history of prostate cancer and gene markers.
• Hormone therapy (androgen deprivation therapy/ADT): The AUA advises that men with low-risk, localized prostate cancer should not be offered ADT, except to shrink tumors prior to brachytherapy (i.e., “radioactive seed therapy”)
• Cryotherapy and high-intensity-focused ultrasound (HIFU): Both are available, although there’s a lack of strong evidence for their effectiveness in comparison to standard treatment options.

Many men on active surveillance have poor compliance with follow-up, so it’s important to confirm the diagnosis with a repeat biopsy or MRI scan before they enter active surveillance. Up to one in three men, given a low-risk diagnosis, turn out to have cancers that are more advanced, and in rare cases they go on to die of an aggressive cancer. Misdiagnosis is most common in African-­American men.

Intermediate-Risk Cancer

• CT or MRI scan: Doctors should consider CT or MRI, or a bone scan, to accurately determine the stage of unfavorable intermediate-risk cancer.
• Standard treatments: Either a) radical prostatectomy (RP) or b) radiation therapy plus androgen deprivation therapy (ADT).
• Cryosurgery: May be considered in some men who are not good candidates for RP or radiation therapy.
• Active surveillance: May be an option for men with favorable ­intermediate-risk cancer who understand and are willing to accept the higher risk of metastasis.
• Watchful waiting: May be an option for older men whose life expectancy is less than five years.
• High-intensity focused ultrasound (HIFU): Clinicians should inform intermediate-risk prostate cancer patients who are considering focal therapy or HIFU that these interventions are not standard care options because comparative outcome evidence is lacking.

High-Risk Prostate Cancer

• CT or MRI scan plus bone scan: To accurately determine staging.
• Radical prostatectomy or radiation therapy plus hormone therapy: Standard treatment.
• Active surveillance: Not recommended for men with high-risk localized prostate cancer.
• Watchful waiting: May be considered in men without symptoms and who have a life expectancy of less than five years.
• Cryosurgery, focal therapy, and HIFU treatments: Not recommended for high-risk, localized cancer unless as part of a clinical trial.
• Hormone therapy alone: Not recommended except in men with a life expectancy of less than five years plus local symptoms.
• Genetic counseling: May be considered for the patient and close family, especially if there is a history of other cancers—breast, ovarian, pancreatic, other gastrointestinal tumors, lymphoma.

In high-risk prostate cancer, there is more urgency about making treatment decisions. The earlier the treatment is initiated, the better the outcome.

Metastatic Prostate Cancer

• Hormone therapy: Standard treatment.
• Pain relief as needed.
• Palliative care if it becomes necessary.

Radical Prostatectomy

Retropubic radical prostatectomy (RP) is the most common surgery for prostate cancer. It produces excellent outcomes, especially in younger men or healthy older men.

Procedure

Prior to surgery, the bowel is evacuated and cleansed to open up space in the pelvis. The surgery is done under general or spinal anesthetic in the operating room. The surgeon accesses the prostate via an incision in the abdomen or the perineum (the area between the scrotum and anus). The entire prostate gland and seminal vesicles are removed—thus the word “radical.” Local lymph nodes are often removed as a precaution.

Surgery is most effective in men with disease isolated to the prostate (stages T1 and T2), who are healthy, and who are under age 70. A hospital stay of one to three days is usual, but it may take several weeks to feel back to normal. Catheterization for at least a week is recommended, to allow the urethra to heal.

During surgery, the surgeon has to weigh certainty against the risk of complications. Removing more tissue and lymph nodes increases the certainty that all of the cancer has been removed, but increases the risk of damaging the nerves to the penis, leading to impotence, and increases the risk of damaging the urethral sphincter, leading to urinary incontinence.

Techniques

There are several radical prostatectomy techniques, including:

Open. Abdominal incision above the pubic bone or perineum. This gives the surgeon an excellent view of the prostate and surrounding organs in the pelvis and the ability to biopsy local lymph nodes (lymph node dissection). This is the preferred technique for more advanced cancers.

Laparoscopic. A flexible laparoscope is inserted via a small incision in the abdomen, suprapubic area, or perineum, and the prostate is removed. Technically, this is much more difficult, requiring expert training. Lymph nodes cannot be dissected.

Robotic. Robotic procedures now account for 60 percent of RP surgeries in the United States. Three to four incisions are made for robotic arms or laparoscopes. One arm carries a laparoscopic video camera, the other surgical tools. The surgeon sits at a screen and operates the robotic arms with a joystick and pedals. Advantages: Improved accuracy, shorter hospital stay, and less blood loss (and, consequently, a lower transfusion rate). Survival rates are similar to open surgery.

In a recent study in Lancet Oncology, 326 men were assigned at random to undergo either open or robotic radical prostatectomy. After two years of follow-up, the men in both groups had essentially the same outcomes in terms of urinary and sexual function. Both procedures appeared to eliminate cancer equally well.

Nerve-Sparing Radical Prostatectomy. This is a prostatectomy with an added technique that attempts to minimize damage to the neurovascular bundles—the nerves and blood vessels that allow the penis to become erect. These are dissected and spared from removal, with the aim to preserve erectile function and lessen urinary problems. This procedure is delicate and time-consuming. The results cannot be guaranteed, and it takes several months for function to begin to recover.

Perineal Incision Technique. In a ­seldom-used approach, the surgeon makes an incision in the perineum, the area between the scrotum and anus, to gain access to the prostate gland and remove it. The advantage of the perineal incision technique is that it’s easier to perform in overweight men and causes less bleeding and pain. The disadvantage is that lymph nodes cannot be biopsied and nerve damage is more common.

Outcomes. For men with localized cancer, radical prostatectomy has a high cure rate. For those with cancer that has spread beyond the prostate, radiation or hormonal therapy may also be needed.

Open, laparoscopic, and robotic radical prostatectomies have similar outcomes in experienced hands, so the decision as to which technique to use should be determined by the surgeon’s expertise and the patient’s preference.

Potential Complications. Early complications, which usually settle in during the first two weeks after surgery, include bleeding, infection (in scar, urine, or prostate), swelling of the penis and scrotum, abnormal changes in the lymph nodes (lymphadenopathy), and heart problems.

In the 2016 ProtecT Trial of 391 men, there were no deaths after prostatectomy. However, nine men had thromboembolic (blood clot) or cardiovascular events, 14 required substantial blood transfusions, one had a rectal injury, and nine developed anastomoses (abnormal connection between two organs).

Persistent complications include nerve damage and erectile dysfunction (20 to 70 percent) and urinary incontinence (50 percent). Some untreated men also develop these complications during active surveillance, but at a rate half that of surgery.

Urinary control and sexual function can improve, with time, after prostatectomy. One study followed 3,187 men for up to four years after surgery. Among men who had urinary incontinence a year after surgery, 30 percent had good urinary function within two years post-op; 49 percent within three years; and 59 percent within four years. For those with impotence at 12 months post-op, erectile function was restored at two years in 22 percent; at three years in 32 percent; and at four years in 40 percent.

Benefits of Surgery. Surgery removes a lot of uncertainty. Research shows that in men with disease isolated to the prostate, 90 percent are alive and cancer-free 10 years after surgery. A coincidental benefit is that you will never develop benign prostatic hyperplasia, a troublesome condition affecting half of men over the age of 60. Open surgery has the advantage of allowing biopsy of lymph nodes to improve certainty over staging and guide further treatment.

Postsurgical Therapy. Some men will be offered radiation or hormone therapy following surgery. It may be recommended in the following situations:

• Adjuvant therapy. For high-risk patients, where cancer was seen on the outer margin of the removed tissue or where cancer had spread to the seminal vesicles. This is usually performed soon after surgery.
• Salvage therapy. For “biochemical recurrence.” A rise in PSA in the months following surgery is seen in 25 to 30 percent of patients. External-beam radiation is usually offered, but some clinicians prefer hormone therapy.

Pre-RP Lymph Node Biopsy. To be certain of staging, some surgeons perform lymph node biopsy to rule out lymph node involvement and steer treatment.

Radiation

Radiation is a viable alternative to radical prostatectomy, with the potential for cure in localized prostate cancer. It carries with it its own set of risks and benefits. There are two forms of radiation therapy commonly used to treat prostate cancer: external-beam radiation therapy (EBRT) and brachytherapy (implanting tiny radioactive pellets, or “seeds,” into the prostate gland).

External-Beam Radiation Therapy (EBRT)

EBRT can be used as a primary treatment for localized cancers, or following surgery, where biopsy reveals spreading beyond the prostatic capsule, or if PSA rises in the postoperative months.

Procedure. Currently the most widely used radiation therapy, EBRT uses focused high-energy x-rays over multiple sessions to destroy the cancer. It can also be used on diseased lymph nodes. The major disadvantage is that EBRT is time-consuming: The patient receives radiation therapy for about 15 minutes each day, five days a week, for about two months. Straps are used to prevent movement and lead shields protect surrounding organs (testicles and penis).

Good Candidates. EBRT is a good option for older men with other health problems in whom cancer has spread outside of the prostatic capsule (Stage 3) and in men who have already had TURP (transurethral resection of prostate) for benign prostatic hyperplasia. It can also be used in advanced cancers to help reduce the size of the prostate and reduce symptoms.

Advanced EBRT. Technological advances with high-dose EBRT have led to improved precision of this technique:

• 3-dimensional conformal radiation therapy (3D-CRT). The radiation beam is shaped to match the tumor and reduce damage to surrounding healthy tissue. Beams of radiation come from several directions to precisely match the tumor’s height, width, and depth.
• Hypofractionated radiation. This newer technique is gaining popularity. It uses higher doses of radiation over four to five weeks. It has a similar side effect and outcome profile to standard EBRT.
• Intensity-modulated radiation therapy (IMRT). This treatment uses state-of-the-art, targeted, high-dose radiation, minimizing damage and side effects. A 3D map of the tumor is created and high-intensity radiation beams are targeted at the affected areas.
• Proton beam therapy (PBT). This treatment uses protons instead of photons (x-rays). Protons are charged particles that radiate energy. Photon beams are narrow and easier to target, scatter less, and may cause less damage to healthy tissue. Early results are showing similar outcomes to EBRT, but gastrointestinal complications are more common. PBT is not available in all centers, and it may not be covered by insurance, although it may be available as part of a clinical trial.
• Stereotactic body radiation therapy (SBRT). Offered as an alternative to conventional radiation fractionation for low-risk patients, but for intermediate- and high-risk patients it should be offered in a clinical trial setting. These techniques (often referred to by brand names like CyberKnife, Gamma­Knife, or TomoTherapy) speed up the process further, to just five days. They deliver high-dose radiation with pinpoint accuracy. Early results are promising but suggest that side effects may be higher. SBRT may be useful for men whose cancer has spread beyond the capsule or for men who have had a TURP. It is available at only a limited number of centers.

Outcomes. Some evidence suggests that survival rates may be slightly lower in men treated with EBRT rather than radical prostatectomy or brachytherapy.

Potential Complications. EBRT has different complications from surgery. Because the beam cannot discern healthy from cancerous tissue, there’s a chance of healthy tissue being damaged. Common complications include:

• Cystitis (inflammation of bladder), blood in urine, urinary retention, and urinary incontinence.
• Proctitis (inflammation of rectum) and enteritis (inflammation of small intestine), which leads to diarrhea, blood in stool, bloating, rectal leakage, and rectal pain. Bowel symptoms can persist for months.
• Impotence takes time to develop after radiation therapy; five years after treatment it is at a similar level to surgery.
• Fatigue may develop during treatment and last weeks or months after treatment has stopped.
• Lymphedema is the swelling of the legs or genitals. It can occur when the lymph nodes—which normally help drain fluid from an area—are damaged by radiotherapy. It can cause significant discomfort.
• Secondary cancers (bladder, colon, and rectum) are a potential but rare complication.

Complication rates vary between technique and dose used. They also depend on pre-treatment function.

Gastrointestinal (GI) complications are most common with proton-beam therapy, while brachytherapy has the lowest risk of GI problems. In an attempt to reduce GI damage, researchers have developed “tissue spacers” to reduce rectal exposure to radiation. For example, the SpaceOAR (Spacing Organs At Risk) System is an FDA-approved hydrogel that is injected as a liquid, quickly solidifying to create a radiation-absorbing barrier between the prostate and rectum.

Secondary cancers may be slightly higher after EBRT. A study published in The BMJ found that EBRT—but not brachytherapy—potentially increased the risk of bladder and colorectal cancer, although the absolute number of cancers was low. They noted “further studies with longer follow-up are required to confirm these findings.” It would be hard to prove categorically that a secondary cancer was due to radiation, and that the cancer wouldn’t have occurred anyway.

Benefits. Radiation therapy is pain-free, and recovery time is much shorter than with surgery. Plus, there is no anesthesia or surgical wound from which to recover. Compared to surgery, immediate complications are less common.

Brachytherapy (BT) or Seed Therapy

Brachytherapy is also known as internal radiation therapy or interstitial radiation therapy.

Procedure. An outpatient procedure, BT takes about 60 minutes to complete. It requires either general or spinal anesthesia. An ultrasound or MRI-guided needle inserts 50 to 150 “seeds”—pellets the size of a grain of rice—throughout the prostate. It’s like having a mini-x-ray machine embedded into the prostate; it works continuously until it runs out of energy, after about a year.

Good Candidates. For standard brachytherapy, men with low-risk cancer and a small prostate are better candidates. For high-dose brachytherapy, intermediate- and high-risk patients are better candidates.

Outcomes. BT survival rates are similar to surgery. However, quality of life tends to be a little better, as urinary incontinence and sexual problems are less common. Research also suggests that survival rates and quality of life are better after brachytherapy than after EBRT.

Complications. Radiation travels only a few millimeters and thus has little effect on the organs external to the prostate. However, the urethra—which lies in the center of the prostate—may be damaged during radiation, leading to urinary problems in most men. Some men require temporary catheterization during treatment. Physical exercise may reduce urinary symptoms. Rarely, bowel symptoms occur, for a month or so. There is a small radiation risk to people around you, so it is advised that pregnant women and children under 18 should avoid sitting on your lap for extended periods, at least in the first two months. In the first two weeks, the seeds can be ejaculated (in 1 percent of patients), so sex should be avoided; later, a condom should be worn during sex. Urine remains radioactive and toxic for months.

Benefits of brachytherapy. Most men recover quickly from the insertion procedure and are pain-free. There is no abdominal or perineal wound to heal. Compared to EBRT, the time commitment is much lower—one procedure and you’re done.

Which Treatment Is Best?

Studies have compared the outcomes for the main treatment options: radical prostatectomy, EBRT, brachytherapy, and active surveillance. The findings show that each option has its own long-term side-effect profile. Here’s a summary of recent research.

One study reported in Cancer Medicine in 2017 measured quality of life 15 years after prostate cancer treatment, comparing RP, EBRT, and BT. The findings were:

• Impairments in urinary irritation/obstruction. Worse in EBRT or BT.
• Decrease in bowel function. Worse in EBRT. However, newer techniques are improving this.
• Long-term change in urinary incontinence. Worse for patients treated with RP compared to BT.

A study in Radiotherapy Oncology looked at quality of life changes 48 months after treatment in the cases of 907 men. Researchers looked at RP, BT, and IMRT. Findings:

• RP. More urinary incontinence, but less urinary irritation and obstruction than radiotherapy. Very low levels of bowel dysfunction.
• Brachytherapy and IMRT. Better sexual function than in those who had surgery, although all groups had symptoms.

The ProtecT Trial was a large randomized study. Researchers followed patients for 10 years and compared surgery (RP), radiotherapy, and active surveillance. The findings include:

• Prostate cancer–specific mortality. At a similar level in all groups—around 1 percent after 10 years. All-cause mortality was similar in all groups at around 10 percent. Risk of death from cancer was 6.6 percent lower after RP compared to active surveillance at eight years follow-up, and 11 percent lower at 23 years.
• Disease progression and metastasis. RP and radiotherapy progression rates were less than half those of active surveillance.
• Active monitoring. Forty-four percent of the patients who were assigned to active monitoring did not receive radical treatment and avoided side effects. Fifty-six percent went on to need treatment over the 10-year period.
• Number needed to treat (NNT). This is a measure of the number of patients receiving treatment to avoid one case of metastatic disease. Here are the statistics compared to active surveillance: prostatectomy NNT = 27; radiotherapy NNT = 33; either prostatectomy or radiotherapy NNT = 9.
• Incontinence. Three years after treatment, the rates of urinary incontinence were 7 percent in high-dose-rate brachytherapy; 5.4 percent in low-dose-rate brachytherapy; and 2.7 percent in EBRT. The rates of erectile dysfunction were 72 percent in high-dose-rate brachytherapy, 36 percent in low-dose-rate brachytherapy, and 68 percent in EBRT.

The researchers point out the importance of recording a patient’s baseline functions and quality of life before treatment begins.

The Scandinavian Prostate Cancer Group study supports the ProtecT findings. Researchers followed 695 men with early prostate cancer who were randomly assigned to one of two groups: radical prostatectomy or watchful waiting.

Researchers followed the men for 23 years. Sixty-three of the RT patients and 99 of the watchful waiting patients died of prostate cancer. They calculated that there was a 44 percent lower relative risk of death from the disease with RP compared to watchful waiting. Younger men and those with intermediate-risk prostate cancer saw the biggest benefits.

Conflicting evidence, however, comes from the Prostate Cancer Intervention Versus Observation Trial (PIVOT). Researchers concluded radical prostatectomy (RP) does not significantly reduce the risk of death from prostate cancer or other causes (5.8 percent) compared with active surveillance (8.4 percent). This difference was deemed to be statistically insignificant. RP did reduce the risk of death from all causes in men with higher PSA levels (higher than 10 ng/ml) and in men with higher-risk tumors.

Cleveland Clinic researchers reported the results of a study of 1,989 patients who underwent brachytherapy. They found that the overall five-year survival rate was 93.7 percent and the 10-year survival rate was 76.1 percent. They concluded that “prostate brachytherapy, as monotherapy, is an effective treatment for low-risk and low-intermediate-risk prostate cancer and appears promising as a treatment for high-intermediate-risk and high-risk prostate cancer. Significant long-term toxicities are rare when brachytherapy is performed as monotherapy.”

In younger men with high-grade prostate cancer, surgery may be the better option, suggests a 2019 study in the Journal of Urology. Researchers found that, in men younger than 60 diagnosed with high-grade cancer, those treated initially with surgery rather than radiation had lower rates of death in general and specifically from prostate cancer.

However, this was an observational study and can’t really tell us for sure whether it was surgery or some other, as-yet unknown factor that was responsible for the improvements in survival. As the researchers noted, “Future prospective randomized trials are needed to confirm the long-term outcomes of these treatment approaches.”

Focal Therapy

Focal therapy, also known as “male lumpectomy,” selectively targets the areas of the prostate affected by cancer. Focal therapies for prostate cancer include high-intensity focused ultrasound (HIFU). The aim of focal therapy is to reduce the complications seen in more invasive open surgery. The research is not conclusive, with some studies showing outcomes comparable to surgery and/or radiation therapy in the short term and fewer long-term side effects.

One limitation of focal therapy is that prostate cancer is often, by its nature, multifocal, appearing in multiple locations in the prostate. Another problem is that cancerous tumors are difficult to pick up on ultrasound or MRI, which are used to guide focal therapy.

AUA treatment guidelines do not generally support the use of focal therapies, saying, “These treatment options lack robust evidence of efficacy.” There is, however, hope that further refinement of focal techniques may prove to be useful in the future.

High-Intensity Focused Ultrasound (HIFU)

HIFU uses precisely targeted doses of ultrasound energy to heat and destroy cancerous prostate tissue.

Procedure. In performing a HIFU procedure, the doctor inserts an ultrasound probe into the rectum, then focuses high-intensity sound waves onto the cancerous areas of the gland. These beams create focused heat that destroys tissue in seconds. HIFU is performed under spinal or general anesthesia and can be done on an outpatient basis.

HIFU has fewer side effects than surgery and radiotherapy, but there is inadequate research on outcomes.

While HIFU has been used for years in Europe and Canada to treat prostate cancer, it is not widely available in the United States, and some health insurance companies won’t cover the procedure. In 2015, the FDA approved HIFU for “prostate tissue ablation”—not specifically for cancer treatment.

Potential Complications. Erectile dysfunction and irritating urinary symptoms (including burning pain while urinating) are common.

Cryotherapy

Cryotherapy, which is conditionally approved by the AUA for local prostate cancer, is the targeted freezing of the prostate to destroy cancer cells. It is also known as cryosurgery or cryoablation. Cryotherapy can be used as a whole-gland treatment or a focal therapy approach.

Procedure. A surgeon uses thin, needle-like probes to enter the prostate through the perineum, and then injects liquid nitrogen into the prostate, freezing and destroying (ablating) cells. Catheterization may be needed for up to a week. The procedure is not widely available.

Good Candidates. The American Urological Association guidelines state that cryotherapy may be considered in men with intermediate-risk localized prostate cancer when radical prostatectomy or radiation therapy are inappropriate due to other health problems. It can also be used to treat cancer that has recurred after primary treatment with surgery or radiation.

Certain men are not good candidates for cryotherapy, including those who have undergone transurethral resection of the prostate (TURP) for benign prostatic enlargement, those with a very large prostate, and those with inflammatory bowel disease.

Outcomes. Cryotherapy can be used to treat the entire prostate gland or as focal therapy to ablate part of the prostate and potentially reduce complications. Some research suggests that local cancer control with cryotherapy is not quite as good as with surgery. Also, unlike surgery, cryotherapy and radiation therapy do not allow for a pathological review of the prostate tissue. Cryotherapy can be combined with ADT, but there is no consensus as to whether this improves outcomes. It is less invasive than surgery and recovery is faster; however, as with radiation, the whole prostate cannot be assessed to accurately determine staging and grading of the disease.

Potential Complications. Complications may be severe, from erectile dysfunction (up to 90 percent) to urinary incontinence (5 percent). Irritation and obstructive urinary problems are common side effects. Rectal fistula also may occur: This is an unpleasant condition where a false connection occurs between the rectum and the perineum (skin between rectum and scrotum), allowing uncontrollable leakage of feces.

A study published in the Journal of Endourology followed 300 men with high-grade prostate cancer after cryotherapy. The study’s researchers looked at whether PSA stayed low (biochemical progression-free survival, or BPFS), and found a two-year BPFS rate of 77 percent and five-year BPFS rate of 59.1 percent. At a 12-month follow-up, 90.5 percent were completely continent and 17 percent were fertile. Rectourethral fistulae occurred in 1.3 percent of patients and severe urinary retention in 3.3 percent.

Androgen-Deprivation Therapy (ADT)

Because prostate cancer originates mainly in the hormone-sensitive glandular cells of the prostate, testosterone and other male sex hormones (androgens) fuel prostate cancer. It makes sense, then, that androgen-deprivation therapy—which reduces levels of androgens in the body and in tumor cells—can slow the progression of cancer, but not cure it. ADT, also called hormonal therapy, can be used alone or in combination with other treatments.

Benefits of Hormone Therapy

ADT can reduce the size of a cancer, reduce symptoms and pain, and may extend life. However, ADT is not a cure, and over time the cancer may begin to grow again, despite the low testosterone.

In men with advanced prostate cancer that is aggressive or has spread beyond the prostate, a combination of hormone (ADT) and radiation therapy reduces the risk of dying by nearly 30 percent compared to radiation alone. Some clinicians use a protocol with intermittent ADT treatment to reduce side effects. PSA levels are monitored and ADT is started when levels creep up; treatment is stopped when PSA drops. In men at intermediate risk, this combination therapy is considered a viable alternative to radical prostatectomy.

ADT Options. Therapies used to reduce androgen levels and slow the progression of prostate cancer include:

• LHRH agonists. Available in one-month, three-month, or six-month injections or annual depots (implant under skin). These drugs stimulate the pituitary gland to produce LH (luteinizing hormone). This causes an initial rise in testosterone, followed by an abrupt decline. Drugs include goserelin (Zoladex), leuprolide (Eligard, Lupron Depot), triptorelin (Trelstar), and the implant histrelin (Vantas).
• LHRH antagonist. Available in a one-month depot. This type of drug blocks the production of gonadotropin-releasing hormone (GnRH) by the pituitary gland, which ultimately decreases production of testosterone in the testes. The drug prevents signals from the pituitary gland to the testicles, thus preventing production of testosterone. The drug of this type currently available in the United States is degarelix (Firmagon).
• Anti-androgens. Also known as androgen antagonists or testosterone blockers, these drugs suppress the action or production of androgens like testosterone. They’re taken in a tablet form. Current anti-androgens in use include apalutamide (Erleada), bicalutamide (Casodex), darolutamide (Nubeqa), enzalutamide (Xtandi), flutamide (Eulexin), and nilutamide (Nilandron). Abiraterone (Zytiga) with prednisone: Abiraterone blocks production of testosterone in prostate cancer cells. It’s taken along with prednisone, a potent anti-inflammatory medication.
• LHRH agonist or antagonist with an oral antiandrogen. This combination of drugs creates a complete androgen blockade.
• Bilateral orchiectomy. This surgery removes both testicles and replaces them with prosthetic ones. Once a common procedure, it is now rarely used.

Good Candidates for ADT

The National Comprehensive Cancer Network and the European Association of Urology recommend androgen deprivation therapy to treat advanced prostate cancer when local therapy has failed. The aim of treatment is to shrink the cancer or slow its growth and give palliative relief (meaning a reduction in severity, even if the condition can’t be cured).

ADT can also help to reduce urinary outlet obstruction and, in lower-risk men, to shrink cancer prior to surgery or radiation. Over time, most cancers stop responding to ADT and progression resumes. Standard treatment lasts 24 to 36 months.

Potential Side Effects. Low androgen levels can cause some unpleasant side effects and seriously affect quality of life. Among them:

• Feeling weak and unwell due to fatigue, anemia, and reduced muscle mass.
• Breast enlargement (gynecomastia).
• Hot flashes.
• Decreased libido and erectile dysfunction (usually improves when treatment stops).
• Increased risk of metabolic syndrome (high blood pressure, high blood sugar, abdominal obesity, and abnormal blood lipids), which increases the risk of cardiovascular disease, stroke, and diabetes.
• Psychological changes and ­cognitive impairment (forgetfulness, inattention, and depression are common).
• Increased risk of diabetes. The relative risk is 30 to 40 percent higher. Monitoring of blood glucose and lipids is advised.
• Increased risk of cardiovascular death. In one study, risk increased to 4.2 percent five years after therapy (1.5 percent in controls) and 13.5 percent 10 years after therapy (5.8 percent in controls).
• Pulmonary edema, or fluid on the lungs, which results in shortness of breath and cough.
• Increased risk of colorectal cancer and liver failure.
• Gastrointestinal tract disturbances, including diarrhea.
• Increased risk of acute kidney injury (5.5 per 1,000 person years), a rare condition with a 50 percent mortality rate.
• Osteoporosis and an increased risk of fractures.

Reducing ADT Side Effects

Cardiovascular Health. Baseline testing of blood glucose and cholesterol should be done. Eating a healthy diet can reduce the risk of obesity, diabetes, and high cholesterol. Regular exercise (with medical supervision) can reduce muscle and bone loss, improve balance, reduce the risk of falls and improve cardiovascular health. One study found that men who exercise when starting androgen deprivation therapy report fewer sexual side effects, less fatigue, and better mood. Cigarette smoking is discouraged, as it increases the risk of many of the complications.

Bone Health. Men with advanced prostatic cancer are at high risk of bone disease. Hormone treatment (ADT) causes osteoporosis and makes some men frail and more prone to falling and fracturing bones.

Drugs such as zoledronic acid (Reclast), denosumab (Prolia), and others may protect against fractures. They are given with calcium and vitamin D. Baseline bone health should be measured before treatment.

Bisphosphonates, such as zoledronic acid (Zometa) and pamidronate disodium (Aredia), may help reduce osteoporosis. These drugs attack osteoclasts—a type of cell that breaks down bone tissue.

Bone metastases (malignant growths in the bone) cause weakness and thinning of the bone, fractures, spinal compression, and pain. Some men require radiation to reduce growth of the metastases and surgery to stabilize weak or fractured bone, and many need pain medication.

Prostate cancer bone metastases are unpleasant and painful, and may lead to pathological fractures. Two drugs, however, have been found to help:

• Denosumab (Xgeva and Prolia) may prevent bone erosion and reduce the impact of cancer spread to bones by blocking RANK-Ligand, a substance that activates osteo­clasts.
• Radium-223 dichloride (Xofigo) is a radioactive drug that emits radiation (alpha particles) into bone metastases. Side effects include low blood counts, nausea, diarrhea, vomiting, and swelling of the leg, ankle, or foot.

Men taking these drugs need to be aware of a rare but serious side effect called osteonecrosis of the jaw. Make sure you discuss your medications with your dentist before starting these treatments or having any dental work.

Chemotherapy

The chemotherapy drug docetaxel (Taxotere) has been found to prolong survival among men with advanced prostate cancer. It may be used along with or after hormone therapy. Doctors administer docetaxel intravenously and in cycles. If docetaxel fails to help, a newer drug, cabazitaxel (Jevtana), may be used. Both prolong survival equally but Jevtana appears to be less toxic.

Chemotherapy can harm normal cells and cause hair loss, nausea, vomiting, anemia, infections, kidney failure, numbness and tingling, fatigue, infertility, excessive bleeding, headaches, and joint pain. Bone marrow suppression is a serious risk, but close monitoring can pre-empt this.

A study in the New England Journal of Medicine followed 790 men with metastatic, hormone-sensitive prostate cancer and concluded that “six cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone.” Men treated with the ADT-docetaxel regimen survived an average of 57.6 months, compared to 44 months for those on ADT alone.

Hormonal Therapy (ADT) with Chemotherapy

In men with metastatic cancer, hormonal therapy may be combined with chemotherapy. A study published in The Lancet randomized 385 men with metastatic cancer to two treatment groups.

The first received ADT alone, the second ADT plus docetaxel (chemotherapy). Men given ADT alone lived, on average, 44 months; those treated with the ADT/chemotherapy combination lived an average 58 months. Improvements were best in the more advanced cancers.

Close monitoring of men on the combined treatment is necessary as it can damage the bone marrow and liver.

Managing Treatment Side Effects. All treatments have side effects. Prostate cancer treatment options run the risk of chronic urinary or sexual health problems. Thankfully there are some treatments that can help.

Immunotherapy (Cancer Vaccines)

Prostate cancer vaccines are designed to help your immune system target and kill cancer cells. Rather than priming your body to kill an infectious disease, these vaccines teach your body how to kill cancer cells.

One such vaccine is sipuleucel-T (Provenge). During the procedure, the patient’s own white blood cells are collected and exposed in the lab to a protein specific to prostate cancer. These activated white cells are then reinfused into the bloodstream, where they begin to attack the cancer cells. Three doses are given intravenously over a month. It is approved for use in men with metastatic disease who no longer respond to ADT, a group in which immunotherapy has been shown to improve life expectancy by about four months.

Other prostate cancer immunotherapies are under study.

The Future: Biomarkers

Biomarkers are specific molecules that indicate a process, normal or abnormal, taking place in your body. PSA is the standard biomarker for prostate cancer; the big problem is that it isn’t specific or accurate enough. Current screening techniques may overdiagnose men with insignificant cancers and miss others with advanced or aggressive disease. Research aims to find biomarkers that can precisely predict clinically significant prostate cancer and accurately guide treatment.

Biomarkers can be measured in blood serum, urine, and tissues. They measure proteins, fragments of proteins, enzymes, DNA, and RNA.

It is likely that what will emerge are several biomarkers—some for diagnosis and some to guide therapy. Urine biomarkers may turn out to be useful, as urine is easily collected and passes through the prostate as it travels along the urethra.

Remarkable stories have been published of dogs that are able to detect cancers—from prostate to lung to breast—with incredible accuracy, suggesting that they’re picking up a particular odor, which may turn out to be a valuable biomarker.

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No one knows for sure what causes prostate cancer, but researchers have identified several genetic factors linked to increased prostate cancer risk. And, recent research provides an estimate of how great the risk of prostate cancer is in men with a family history of the disease.

According to the American Cancer Society, your personal risk of prostate cancer doubles if your father or brother had the disease, and it’s even greater if several of your relatives had it, particularly if they were young when they were diagnosed.

Is Prostate Cancer Hereditary? Research Addresses Genetics

A recent study has estimated how greatly your family history might influence your risk of prostate cancer. Researchers reviewed data on nearly 52,000 Swedish men with brothers and fathers who had prostate cancer. Compared with the general population, men with a brother who had prostate cancer were more than twice as likely to be diagnosed with prostate cancer and faced nearly twice the risk of developing an aggressive form by age 75.

And, the study found, men with both a father and brother who had prostate cancer faced more than a threefold increased risk of being diagnosed with prostate cancer and a nearly threefold risk of aggressive prostate cancer by age 75, compared with the general population.

The likelihood of developing aggressive prostate cancer was about as great in men whose fathers or brothers had lower-risk prostate cancer as those whose relatives had aggressive prostate cancer, the researchers reported (Journal of the National Cancer Institute, October 2016).

“We had expected that the risk of aggressive prostate cancer would be particularly lower in men with favorable cancer in the family, but that wasn’t the case,” study author Ola Bratt, a researcher at Lund University, in Sweden, said in a statement. “Men whose fathers or brothers had a favorable prostate cancer don’t usually think that increases their own risk of developing aggressive cancer. They might not even know that they have prostate cancer in the family.”

Understand Your Genetic Risks

So, is prostate cancer hereditary? The answer may lie in the dozens of genetic mutations, or variants, that have been associated with varying degrees of prostate cancer risk, as well as the additional suspect genes that are being researched. Having one of these genetic defects does not mean you will get prostate cancer, but it does increase the likelihood, which is probably why some families have a history of prostate cancer.

For instance, if a woman in your family developed breast cancer caused by mutations in the BRCA1 and BRCA2 genes, you may face a greater risk of prostate cancer. Moreover, some evidence suggests that men with BRCA-related prostate cancers, especially those tied to BRCA2, are more likely to present with more advanced and aggressive disease, and they also might have worse survival outcomes after prostate cancer surgery.

In one study, researchers found that 8 percent of men with BRCA1 mutations and 5 percent with BRCA2 mutations were diagnosed with prostate cancer, rates higher than those in the general population (American Urological Association 2017 Annual Scientific Meeting).

Another analysis found that 71 percent of BRCA2 prostate cancer patients presented with higher-risk disease at the time of their diagnosis, had poorer survival rates, and were four times more likely than men without the genetic mutation to present with metastatic disease (American Urological Association 2016 Annual Scientific Meeting).

Further Prostate Cancer Risk Factors

Some evidence suggests that an inherited genetic condition, Lynch syndrome, which has been linked to a greater risk of colorectal cancer and several other malignancies, also may be associated with a higher risk of prostate cancer.

Keep in mind that these inherited genetic disorders account for a relatively small percentage of prostate cancers—about 5 to 10 percent, according to the American Cancer Society. Still, if you have a strong family history of prostate cancer or any of these genetic abnormalities, it’s especially important to talk to your doctor about your individual risk of the disease and your need for earlier and more intensive prostate cancer screening.

The same recommendation applies if you’re African-American. Prostate cancer occurs more commonly in African-American men and less so in Asian-American and Hispanic men. Rates of fatal prostate cancer also are significantly higher among African-Americans.

In fact, the risk of preclinical prostate cancer among black men is 28 to 56 percent higher than that in the general population, and although black men are about as likely as men of other races to be diagnosed with prostate cancer, their risk of progression to metastatic disease at the time of diagnosis is 44 to 75 percent higher than that in the general population, according to a recent study.

“The findings suggest screening black men earlier than white men, and support further research into the benefit-harm trade-offs of more aggressive screening policies for black men,” the researchers concluded (Cancer, June 15, 2017).

This article was originally published in 2018. It is regularly updated. 

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Scientists do know that prostate cancer symptoms occur when changes or mutations in the DNA of prostatic cells cause abnormal proliferation of those cells, resulting in a tumor that can remain localized to the prostate gland or spread to other parts of the body.

While having one or more of the known risk factors for prostate cancer does not necessarily mean you will develop prostate cancer, it does mean your risk is increased.

12 Risk Factors for Prostate Cancer

• Age: Age is the most significant risk factor for prostate cancer with increasing age associated with an increasing risk. The Centers for Disease Control and Prevention estimates that roughly 2.5 out of every 100 50-year-old men will develop prostate cancer by age 60, and that 7.5 out of every 100 70-year-old men will develop it by age 80.
• Race: African-American men are more likely to develop prostate cancer and die from it than Caucasian men.
• Family history: Having a father or brother with prostate cancer increases your prostate cancer risk. Some research suggests this risk is two to three times higher than in men with no family history. The risk is increased if the first degree relative was diagnosed before the age of 60 or if you have more than one first degree relative with prostate cancer.
• Genes: Scientists have identified certain genes associated with an increased risk for prostate cancer, although there is currently only a test for one, a mutation in the BRCA2 gene known better for its risk of breast and ovarian cancer.
• History of another cancer: Having had melanoma, thyroid cancer, bladder cancer, lung cancer, or kidney cancer slightly increases your risk for prostate cancer.
• Height and weight: Evidence suggests that obese men are at increased risk of developing aggressive prostate cancer and of dying from their prostate cancer. Some research has also indicated that taller men have an increased risk of developing aggressive prostate cancer and metastatic prostate cancer compared with shorter men.
• Smoking: A history of smoking has been linked to an increased risk of aggressive prostate cancer in some studies. The relationship between smoking and prostate cancer risk appears to be dose-dependent such that men who smoke the most have the highest risk of developing aggressive prostate cancer.
• Vitamin E supplements: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) demonstrated that men who took vitamin E supplements alone had a 17 percent increased risk of prostate cancer.
• Geography: Men living in North America, the Caribbean, northwestern Europe, and Australia have a higher incidence of prostate cancer than men living in Africa, Asia, Central, and South America. The reasons for this are unclear, though some scientists suspect that differences in resources for diagnosis or dietary factors may play a role. Interestingly, Asian-American men have a higher risk of prostate cancer than men of a similar background living in Asia.
• High-calcium diet: A large European study of more than 142,000 men found an increased risk of prostate cancer with high dietary intake of calcium from dairy products, though not in men whose calcium came from non-dairy sources. A large U.S. study also found a link between high consumption of calcium and dairy and prostate cancer.
• High-in-fat diet: Some studies have shown that men with high dietary fat consumption, particularly animal fat, have an increased risk of prostate cancer. As a result, some doctors encourage patients to get their fat from plant sources such as olive oil, nuts, or seeds and to reduce their total fat intake.
• Abnormal changes in the prostate cells: Scientists have identified two non-cancerous conditions of the prostate diagnosed by biopsying prostate tissue that some research suggests might be precursors to prostate cancer. High-grade prostatic intraepithelial neoplasia (PIN) in which the cells look abnormal but are not yet cancerous is one of these conditions. Studies have demonstrated that 20 percent of men with high-grade PIN have cancer in another part of the prostate. The other condition is Proliferative inflammatory atrophy (PIA) in which the prostate cells are smaller than usual and have signs of inflammation. There is some evidence that having PIA might increase your risk of high-grade PIN or prostate cancer.

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Furthermore, a variety of factors can affect the PSA level. In addition to prostate cancer, BPH, and prostatitis, normal PSA levels can be influenced by a urinary tract infection, a prostate biopsy or surgery, bladder tests, and recent ejaculation. Some medications including nonsteroidal anti-inflammatory drugs (NSAIDs), thiazide diuretics, statins, as well as some medications used to treat BPH may lower your PSA level.

Normal PSA Level Results: Reliable?

Most experts agree that the higher the PSA level, the more likely it is that a man has prostate cancer. However, the PSA test is not fool-proof. In fact, some evidence has shown that only 25 percent of men who underwent a prostate biopsy because of a higher PSA actually had prostate cancer.

Studies have also demonstrated that as many as 17 to 50 percent of men with elevated PSAs have a prostate cancer that’s slow-growing and that does not cause symptoms during their lifetime. As a result, there is some concern that these men are being over-diagnosed and subjected to unnecessary risks and consequences of their diagnosis.

These consequences may include erectile dysfunction symptoms, infection, or bleeding. The psychological toll of knowing you have cancer may cause significant anxiety and stress. If these men opt to undergo biopsy and/or treatment, they may be exposing themselves unnecessarily to possible side effects (infection, urinary incontinence, erectile dysfunction, etc.).

Are There Official Recommendations About PSA Testing?

There is conflicting opinion about PSA testing for prostate screening among different organizations. This is in part due to conflicting data from a number of large studies on PSA testing.

The National Cancer Institute conducted a Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, comparing men who underwent annual PSA and DRE screenings with men who were not screened. Findings showed that early identification of prostate cancer did not result in lower death rates—and may have led to over-treatment.

On the other hand, a large European trial found men screened with PSA had both a higher incidence and a lower death rate than men who were not screened. In 2012, the United States Preventive Services Task Force (USPSTF) concluded that the benefits to PSA screening did not outweigh the potential harms associated with over-diagnosis and over-treatment. A recent study determined that PSA screening has declined 18 percent since these recommendations were issued and that the detection of early-stage prostate cancer has also declined while the detection of late-stage cancer has remained the same, further fueling the debate over PSA screening.

Age-specific screening recommendations differ among various health organizations, including the American Urological Association (AUA) and the American Cancer Society (ACS). Most organizations agree, however, that screening should be individualized based on risk factors, age, and overall health, whether or not you are experiencing prostate cancer symptoms, along with open dialogue between patient and healthcare provider.

Men at higher risk, whether because of family history or race, may want to begin that dialogue with their healthcare providers at an earlier age. Older men, particularly those older than 75 or those with a life expectancy of less than 10 years, may not need to be screened.

Originally published in 2016, this post is regularly updated.

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A digital rectal exam is not painful, but it’s not comfortable, either. According to Cancer.net, you should tell your doctor if you have hemorrhoids or anal fissures, as a digital rectal exam may aggravate them. Fortunately, it doesn’t take the physician long to do a digital rectal exam—rarely more than a minute or two.

Your doctor may do a digital rectal exam more frequently if you are experiencing any problems, such as a change in bowel habits, bleeding or discharge, or urinary problems.

What a Digital Rectal Exam Is For

In a digital rectal exam, the physician will evaluate the anal sphincter strength, which is valuable in cases of fecal incontinence; check for internal hemorrhoids; and feel for nodules or masses. The digital rectal exam is not a colon-cancer test on its own because the exam is limited by the length of the physician’s finger reach. (See sidebar.)

For women, a digital rectal exam also allows the physician to feel for abnormalities in the area between the rectum and the vagina. Some physicians will press on the pelvic area while performing the digital rectal exam in order to palpate the ovaries and uterus. The woman’s position for a digital rectal exam is the same as for a pap smear—on her back, feet in the exam-table stirrups.

For men, the primary reason for a digital rectal exam is to palpate the prostate, which sits right in front of the rectum. The most common positions for the digital rectal exam: standing and bent over at the waist or lying on an exam table in the fetal position, knees pulled up. Apprehension about the digital rectal exam is a primary reason many men avoid wellness exams.

Is The Male Digital Rectal Exam Worthwhile?

Some experts believe a blood test called the PSA (prostate-specific antigen) makes the digital rectal exam unnecessary for men. PSA is a protein that is often elevated in men with prostate cancer. However, in 2012, the U.S. Preventive Services Task Forces (USPSTF) recommended against routine PSA testing; it may lead to over-treatment of slow-growing, non-harmful tumors and unnecessarily risky prostate biopsies, according to the USPSTF. Our post “It Isn’t Time to Abandon the Prostate-Specific Antigen Test Just Yet” discusses the pros and cons.

The committee didn’t address the digital rectal exam. However, according to Ryan Terlecki, M.D., “The evidence suggests that in most cases, it is time to abandon the digital rectal exam.” Dr. Terlecki, a Wake Forest Baptist urologist, published an article on the topic in Current Medical Research and Opinion.

To reach his conclusion, Dr. Terlecki and his researchers reviewed records of 38,340 men who received an annual digital rectal exam and PSA test for three years. The subjects were followed for up to 13 years. Of particular interest were the 5,064 men who had a normal PSA test but an “abnormal” digital rectal exam. Only 2 percent of these men had clinically relevant prostate cancer.

“When PSA testing is used, the digital rectal exam rarely assists in diagnosing significant disease,” said Terlecki. “In cases where PSA testing is used, the digital rectal exam should be abandoned in common clinical practice.”

For related reading, see these posts:

• “Uterine Cancer: Symptoms Can Lead to Early Diagnosis“
• “Prostate Cancer Symptoms? PSA Test Is Only Part of the Story”
• “How to Treat an Impacted Bowel“
• “An Abnormal PSA Result: What Comes Next?“

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New methods seek to clarify diagnoses in men whose PSA is considered “borderline”—i.e., a range of between 4 nanograms per milliliter (ng/ml) and 10 ng/ml. The idea is to have these “fine-tuned” PSA tests help identify encapsulated, slow-growing cancers that may be eligible for a so-called “watchful waiting” treatment plan.

This does not mean that you and your doctor are ignoring any symptoms of prostate cancer you may be manifesting. If you receive a prostate cancer diagnosis, “active surveillance” will mean periodic checks using the following PSA test variations, and may also include biopsy.

• PCA3: This is a genetic urine test that provides a PCA3 score. Men with a higher PCA3 score are more likely to have prostate cancer cells detected on biopsy than men with a low PCA3 score. The U.S. Food and Drug Administration (FDA) has approved this test for men 50 or older who have had one negative prostate biopsy and for whom a repeat biopsy is recommended based on current standard of care.

• PSA velocity: This test determines the rate at which your PSA changes over time and is reported as ng/ml per year.

• PSA doubling time: This is the amount of time elapsed while your PSA level doubles.

Variations on the traditional prostate specific antigen (PSA) test are improving diagnoses and limiting unnecessarily aggressive treatments that can have devastating side effects.

• Free vs. total PSA: PSA in the blood can be circulating independently (“free”) or attached to other proteins. Men with a high total PSA but low free PSA are more likely to have prostate cancer.

• PSA density: This test divides the PSA level by the volume of the part of the prostate gland that surrounds the urethra. There is some evidence that this value can be useful in detecting prostate cancer.

• Pro-PSA: Having a form of free PSA called pro-PSA has been linked to an increased risk of aggressive prostate cancer.

For further reading on related topics, see the following University Health News posts:

• “Are You Keeping Tabs on Your PSA Levels?“
• “An Abnormal PSA Result: What Comes Next?“
• “Prostate Cancer Stages“
• “Prostate Cancer Symptoms? PSA Test Is Only Part of the Story“

Originally published in May 2016 and updated.

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