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Prostate cancer is the most common non-skin cancer in America, affecting 1 in 6 men. But who is most at risk of getting prostate cancer and why?

There are several major factors that influence risk, some of them unfortunately cannot be changed.

Age: The older you are, the more likely you are to be diagnosed with prostate cancer. Although only 1 in 10,000 men under age 40 will be diagnosed, the rate shoots up to 1 in 38 for ages 40 to 59, and 1 in 15 for ages 60 to 69.

In fact, more than 65% of all prostate cancers are diagnosed in men over the age of 65. The average age at diagnosis of prostate cancer in the United States is 69 years. After that age, the chance of developing prostate cancer becomes more common than any other cancer in men or women.

Race: African American men are 60% more likely to develop prostate cancer compared with Caucasian men and are nearly 2.5 times as likely to die from the disease. Conversely, Asian men who live in Asia have the lowest risk.

Family history/genetics: A man with a father or brother who developed prostate cancer is twice as likely to develop the disease. This risk is further increased if the cancer was diagnosed in family members at a younger age (less than 55 years of age) or if it affected three or more family members.

In addition, some genes increase mutational rates while others may predispose a man to infection or viral infections that can lead to prostate cancer.

Where you live: For men in the U.S., the risk of developing prostate cancer is 17%. For men who live in rural China, it’s 2%. However, when Chinese men move to the western culture, their risk increases substantially.

Men who live in cities north of 40 degrees latitude (north of Philadelphia, PA, Columbus, OH, and Provo, UT, for instance) have the highest risk for dying from prostate cancer of any men in the United States. This effect appears to be mediated by inadequate sunlight during three months of the year, which reduces vitamin D levels.

Risk Factors in Aggressive vs. Slow-Growing Cancers
In the past few years, we’ve learned that prostate cancer really is several diseases with different causes. The more aggressive and fatal cancers likely have different underlying causes than slow-growing tumors.

For example, while smoking has not been thought to be a risk factor for low-risk prostate cancer, it may be a risk factor for aggressive prostate cancer. Likewise, lack of vegetables in the diet (especially broccoli-family vegetables) is linked to a higher risk of aggressive prostate cancer, but not to low-risk prostate cancer.

Body mass index, a measure of obesity, is not linked to being diagnosed with prostate cancer overall. In fact, obese men may have a relatively lower PSA levels than non-obese men due to dilution of the PSA in a larger blood volume. However, obese men are more likely to have aggressive disease.

Other risk factors for aggressive prostate cancer include:
Φ Tall height
Φ Lack of exercise and a sedentary lifestyle
Φ High calcium intake
Φ African-American race
Φ Family history
Research in the past few years has shown that diet modification might decrease the chances of developing prostate cancer, reduce the likelihood of having a prostate cancer recurrence, or help slow the progression of the disease. You can learn more about how dietary and lifestyle changes can affect the risk of prostate cancer development and progression in PCF’s Nutrition, Exercise and Prostate Cancer guide.

Risk and Other Prostate Conditions
The most common risk misperception is that the presence of non-cancerous conditions of the prostate will increase the risk of prostate cancer.

While these conditions can cause symptoms similar to those of prostate cancer and should be evaluated by a physician, there is no evidence to suggest that having either of the following conditions will increase a man’s risk for developing prostate cancer.

■ Benign Prostatic Hyperplasia (BPH) is a non-cancerous enlargement of the prostate. Because the urethra (the tube that carries urine from the bladder out of the body) runs directly through the prostate, enlargement of the prostate in BPH squeezes the urethra, making it difficult and often painful for men to urinate. Learn more about BPH.
■  Prostatitis, an infection in the prostate, is the most common cause of urinary tract infection in men. Most treatment strategies are designed to relieve the symptoms of prostatitis, which include fever, chills, burning during urination, or difficulty urinating. There have been links between inflammation of the prostate cancer and prostate cancer in several studies. This may be a result of being screened for cancer just by having prostate related symptoms, and currently this is an area of controversy. Learn more about prostatitis.
More Myths and Non-Risks
Sexual Activity - High levels of sexual activity or frequent ejaculation have been rumored to increase prostate cancer risk. This is untrue. In fact, studies show that men who reported more frequent ejaculations had a lower risk of developing prostate cancer.

Having a vasectomy was originally thought to increase a man’s risk, but this has since been disproven.

Medications - Several recent studies have shown a link between aspirin intake and a reduced risk of prostate cancer by 10-15%. This may result from different screening practices, through a reduction of inflammation, or other unknown factors.

The class of drugs called the statins - known to lower cholesterol - has also recently been linked to a reduced risk of aggressive prostate cancer in some studies.

It’s worth noting that one recent study did show a nearly twofold risk of developing prostate cancer in men exposed to Agent Orange.
Alcohol - There is no link between alcohol and prostate cancer risk.
Vitamin E - Recent studies have not shown a benefit to the consumption of vitamin E or selenium (in the formulations studied) in the prevention of prostate cancer.
(Some of the information on this page is adapted from Dr. Patrick Walsh's Guide to Surviving Prostate Cancer.)

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Not everyone experiences symptoms of prostate cancer. Many times, signs of prostate cancer are first detected by a doctor during a routine check-up.

Some men, however, will experience changes in urinary or sexual function that might indicate the presence of prostate cancer. These symptoms include:
■A need to urinate frequently, especially at night
■Difficulty starting urination or holding back urine
■Weak or interrupted flow of urine
■Painful or burning urination
■Difficulty in having an erection
■Painful ejaculation
■Blood in urine or semen
■Frequent pain or stiffness in the lower back, hips, or upper thighs
You should consult with your doctor if you experience any of the symptoms above.
Because these symptoms can also indicate the presence of other diseases or disorders, such as BPH or prostatitis, men will undergo a thorough work-up to determine the underlying cause.

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Prostate Cancer Grading
As part of the diagnosis process, prostate cancer is graded and staged. The grade describes how aggressive the cancer is and how fast it is likely to grow.

Most pathologists use the Gleason scale to grade prostate cancer. They look for the most common type of cancer cell in the sample and assign it a number between 1 and 5 — the higher the number, the more abnormal the cells are. Another number is assigned to the second most common type of cell in the sample. The Gleason score is the sum of these two numbers (which will be between 2 and 10).

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Surgery
Surgery is a common treatment for early stage prostate cancer and may be recommended for patients who are in good health and younger than age 70.

Radical prostatectomy is usually recommended for early-stage cancer that has not spread to other tissues or organs. This procedure makes the patient essentially "cancer free."

During a radical prostatectomy the surgeon removes the entire prostate gland and sometimes lymph nodes, along with both seminal vesicles, both ampullae (the enlarged lower sections of the vas deferens) and other surrounding tissues. In "nerve-sparing" radical prostatectomy, the nerves to the penis that control erections are preserved.

Radical prostatectomy typically requires general anesthesia and takes two to four hours. The patient stays in the hospital for three days, and needs to wear a tube to drain urine for 10 days to 3 weeks. Newer techniques for radical prostatectomy such as laproscopic and robotic prostatectomy are also available.

Possible side effects of radical prostatectomy
Surgery-related complications, such as bleeding, infection or cardiovascular problems
Loss or urinary control, called incontinence
Loss of the ability to achieve or maintain an erection
Side effects may be temporary or permanent, depending upon the patient’s age, extent of disease and type of surgery

Radiation Therapy
Also known as "irradiation" or "radiotherapy", radiation therapy uses high energy X-rays, either from a machine (external beam radiation therapy) or emitted by radioactive seeds implanted in the prostate ("seed implantation" or brachytherapy, to kill cancer cells. When prostate cancer is localized, radiation therapy serves as an alternative to surgery or it may be used after surgery to kill remaining cancer cells.

External beam radiation therapy generally involves treatments 5 days a week for 6 to 7 weeks. If the tumor is large, hormonal therapy may be started at the time of radiation therapy and continued for several years.

Possible side effects of external beam radiation therapy
Diarrhea
Inflammation of the rectum ("radiation colitis")
Inflammation of the bladder ("radiation cystitis")
Problems with urination
Fatigue
Impotence
With "seed implantation" or brachytherapy, the implantation procedure is completed in an hour or two under local anesthesia; the patient typically goes home the same day.

Possible side effects of brachytherapy
Post-implant pain in the rectum
Incontinence
Difficulty in urination (frequency, retention)
Inflammation of the prostate (uncommon)
Sexual impotence (uncommon)

There is no “one size fits all” treatment prostate cancer. You should learn as much as possible about the many treatment options available and, in conjunction with your physicians, make a decision about what’s best for you. Because men diagnosed with localized prostate cancer today will likely live for many years, any decision made now will likely reverberate for a long time.

Your decision-making process will likely include a combination of clinical and psychological factors, including:
■The need for therapy
■Your level of risk
■Your personal circumstance
■Your desire for a certain therapy based on risks, benefits, and your intuition
Consultation with all three types of prostate cancer specialists—a urologist, a radiation oncologist, and a medical oncologist—will give you the most comprehensive assessment of the available treatments and expected outcomes. Many hospitals and universities have multidisciplinary prostate cancer clinics that can provide this three-part consultation service.

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Red indicates more severe dysfunction
These figures are shown for men with normal function prior to therapy.

Reproduced from the Journal of Clinical Oncology 2009; 27: 3916-3922.

Of course, exact figures will differ across institutions and surgeons or radiation oncologists. The figures here are only meant to be a guide to help understand these risks over time. The numbers will also differ if there is already dysfunction present prior to surgery or radiation, as the risks of side effects are increased in this setting.

While erectile dysfunction rarely improves with any local therapies compared with before therapy, urinary obstruction symptoms can often improve after surgery and occasionally after radiation. Urinary incontinence can also improve after these local therapies.

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The Role of PSA

PSA as a Marker for Disease Progression
When it comes to assessing disease progression, PSA is widely accepted as an invaluable tool.

PSA is produced by all prostate cells, not just prostate cancer cells. At this point in your journey, your cancer cells have either been removed or effectively killed after being bombarded with radiation. But some cells might have been able to spread outside the treatment areas before they could be removed or killed. These cells at some point begin to multiply and produce enough PSA that it can again become detectable by our lab tests.

Therefore, PSA is not really a marker for disease progression, but a marker for prostate cell activity. Because the two correlate well after initial treatment for local therapy, tracking the rise of PSA in this setting is an important way of understanding how your prostate cancer is progressing.

However in order to determine whether your PSA is rising, you need to first determine where it is rising from. Often, imaging tests will not be able to determine this when the PSA is at very low levels, however. Tests such as bone scans, Prostascint scans, and CT/MRI scans in this setting are often negative and thus most decisions on the next therapy (ie radiation or hormonal therapy) are based on probabilities of cure with radiation rather than by seeing the cancer on scans. Prostascint scans in this setting are often not very helpful, given their high false positive and false negative rates, and thus can be misleading.

After prostatectomy, the PSA drops to "undetectable levels," typically given as < 0.05 or < 0.1, depending on the lab. This is effectively 0, but by definition we can never be certain that there isn’t something there that we’re just not picking up. By contrast, because normal healthy prostate tissue isn’t always killed by radiation therapy, the PSA level doesn’t drop to 0 with this treatment. Rather, a different low point is seen in each case, and that low point, or nadir, becomes the benchmark by which to measure a rise in PSA.

Because the starting point is different whether you had surgery or radiation therapy, there are two different definitions for disease recurrence as measured by PSA following initial therapy.

In the post-prostatectomy setting, the most widely accepted definition of a recurrence is a PSA > 0.2 ng/mL that is seen to be rising on at least two separate occasions at least two weeks apart and measured by the same lab. In the post-radiation therapy setting, the most widely accepted definition is a PSA that is seen to be rising from nadir in at least three consecutive tests conducted at least two weeks apart and measured by the same lab. It’s important to always use the same lab for all of your PSA tests because PSA values can fluctuate somewhat from lab to lab.

The reason that we need to look for confirmation from multiple tests following radiation is that the PSA can "bounce" or jump up for a short period after radiation therapy, and will then come back down to its normal level. If we relied only on the one elevated PSA, it’s possible that we will have tested during a bounce phase, and the results will therefore be misleading. This PSA bounce typically occurs between 12 months and 2 years following the end of initial therapy.

If your PSA is rising but doesn’t quite reach these definitions, your doctor might be tempted to start initiating further therapy anyway. Remember that PSA is only one of many factors that help to determine your prognosis after treatment. The original clinical stage of disease, your pre-diagnostic PSA, and your overall health and life expectancy are also key factors in assessing the aggressiveness of your disease, so be prepared to discuss treatment options even if you don’t fit the classical categories for PSA rise after initial therapy.

On the other hand, if your PSA is rising and you do fit the categories defined above, that doesn’t necessarily mean that your situation is dire. What researchers have been finding over the past few years is that universal PSA cut-offs might not be sufficient for truly understanding how prostate cancer grows.

PSA Velocity
Suppose one man underwent intensity-modulated radiation therapy (IMRT), and his PSA nadir was 0.15 ng/mL. Over the course of nine months, it slowly creeps up until it hits 0.45. But his brother, who also underwent IMRT, nadired at 0.32 ng/mL. If after the same progression over the course of nine months his PSA also rose to 0.45, are they now in the same place? Or is there some significance to the fact that one man’s PSA rose much more rapidly than his brother’s?

The rate at which your PSA rises after prostatectomy or radiation therapy can be a very significant factor in determining how aggressive your cancer is, and can therefore be useful in determining how aggressively it might need to be treated.

When looking at PSA velocity in a few hundred men who had undergone either prostatectomy or radiation therapy, researchers found that men whose PSA doubled in under three months had the most aggressive tumors and were more likely to die from their disease, whereas those whose PSA doubled in more than ten months had the least aggressive tumors and were less likely to die from their disease.

If we go back to our two hypothetical cases, although both have a PSA of 0.45 ng/mL, the first one, whose PSA rise represents a doubling within nine months after treatment, would likely be considered for an aggressive therapeutic regimen. And the second case with the smaller rise in PSA? He might be watched closely to see how rapidly his PSA rises, and to determine when it might be time to intervene.

However, PSA doubling time or velocity does not always remain the same over time. So even if you have a very slowly rising PSA now, continued monitoring with your doctor is important. Also, if you’ve consistently kept to a very low PSA rate after treatment, any rise will likely be seen as a signal that the tumor might be starting to grow again.

Measuring and using PSA velocity is an art, not a science. There’s no magic number of times that your PSA has to be tested in order to determine the rate of rise, although most researchers would agree that more frequent tests over longer periods of time will likely give a better sense of how your tumor is growing.

Ultimately, PSA is only one of many factors that can influence the decision to pursue additional treatments. You and your doctors will need to weigh all of the different factors before deciding on the course that’s right for you.

Radiation Therapy Following Prostatectomy

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