Prostate Cancer

The risk of developing prostate cancer varies with ethnicity, with African American men at the highest risk. Risk is also elevated in men with a family history of the disease and increases in general as men age. About 60% of all prostate cancers are diagnosed in men over the age of 65.

More is being learned about the genetic components of prostate cancer risk. For example, men with certain mutations (disease-causing variants) in the BRCA1 and BRCA2 genes have an increased lifetime risk of prostate cancer. However, these mutations probably account for only a small percentage of prostate cancers overall and most men will not be tested for BRCA mutations. For those who are tested, the presence of such variants may influence the decisions about screening and treatment options.

Cancer that develops in the prostate may stay localized (entirely contained within the prostate) for many years and cause few noticeable symptoms. Most cases of prostate cancer are slow-growing, and symptoms begin to emerge only when the tumor mass grows large enough to constrict the urethra. This can cause symptoms such as:

• Frequent urination, especially at night
• A weak or interrupted urine stream
• Pain or burning upon urination or ejaculation
• Pus or blood in urine or semen
• Discomfort in the lower back, pelvis, or upper thighs

Many of these symptoms, however, can also be caused by other conditions, such as benign prostatic hyperplasia (BPH), a urinary tract infection (UTI), acute inflammation of the prostate, or a sexually transmitted disease.

BPH is a non-cancerous enlargement of the prostate that is very common in men as they age. According to the American Urological Association, it can affect as many as 90% of men by the time they are 80 years old. It does not cause prostate cancer, but both may be found together. Through testing, healthcare practitioners must determine whether a man's symptoms are due to prostate cancer, BPH, or to another non-cancer-related condition. This may involve lab tests (such as PSA) and digital rectal exam (DRE) and, depending on the results of those, a prostate biopsy.

Men who have no symptoms must decide, along with their healthcare practitioners, whether to undergo screening for prostate cancer. Many health organizations recommend that men discuss the advantages and disadvantages of screening for prostate cancer with their healthcare practitioner before making an informed decision about screening.

If you choose to be screened, the following tests may be recommended:

• Prostate specific antigen (PSA)—blood test that measures the level of PSA in the blood
• Digital rectal exam (DRE)—part of a physical exam that the healthcare practitioner performs to manually examine the prostate gland; to perform the DRE, a healthcare practitioner inserts a gloved, lubricated finger into the rectum and feels the prostate gland to detect abnormalities.

Considerations

One important factor to consider when deciding whether to undergo screening is your personal risk of developing prostate cancer:

• Average risk—includes healthy men with no known risk factors
• Increased risk—African American men or men who have a father or brother who was diagnosed before they were 65 years old; men with disease-causing genetic variants (e.g., BRCA2 mutation)
• High risk—includes men with more than one relative who was affected at a young age

There are many other factors to consider, including the potential benefits and harms of screening. You should know that:

• Results from long-term trials on whether PSA testing improves prostate cancer survival rates have been inconclusive.
• Screening tests for PSA do not detect all cases.
• A potential benefit of PSA screening is detecting cancer early when it is most treatable (which could potentially lower the risk of cancer death for some men). Also, screening may detect any prostate cancer for men who value knowing their cancer status over possible PSA screening harms.

If your PSA level is elevated, you should know that:

• While elevated PSA levels are associated with cancer, elevated PSA may be caused by other conditions, such as benign prostatic hyperplasia (BPH) and inflammation of the prostate. A false-positive test result could lead to stress and unnecessary tests, including a prostate biopsy.
• Since PSA can be elevated temporarily for a variety of reasons, a repeat PSA test may be done a few weeks after an initially elevated result to determine if it is still elevated and to avoid diagnosing cancer when it may never cause harm (overdiagnosis). If the repeat test is elevated, your healthcare practitioner may recommend that a series of PSAs be done over time to determine whether the level goes down, stays elevated, or continues to increase. You may choose this approach, called "watchful waiting," instead of undergoing a biopsy.
• If you have an elevated PSA or series of elevated PSAs, a decision must be made about undergoing a biopsy. A prostate biopsy has a small risk of complications such as pain, infection and bleeding. For more on biopsies, read the article on Anatomic Pathology. Also, see Tests below for information on additional tests that may be done to help decide about whether to undergo a biopsy.

If prostate cancer is diagnosed, consider that:

• Current technology cannot tell a slow-growing cancer from a fast-growing one. Most prostate cancers are slow-growing and may never significantly affect a man's health or life expectancy.
• If the cancer is slow-growing, the treatments for prostate cancer may be worse than the cancer as they can cause side effects such as erectile dysfunction and incontinence.
• Some men may attempt to avoid harms of treatment by choosing not to treat immediately but opting for "watchful waiting," or "active surveillance" that involves PSA tests done about every six months with digital rectal exams and prostate biopsies (annually) to monitor the cancer.
• Some prostate cancers, however, do grow and spread aggressively into the pelvic region and then throughout the body; and some slow-growing cancers eventually become large and symptomatic enough that they require medical intervention. The challenge is to detect prostate cancer, evaluate its growth rate and spread, and for you and your healthcare practitioner to decide if treatment is to be given and, if so, when.

Recommendations: If you choose screening, there are differences in recommendations on when to start screening and how often it should be done. For details, see Screening Tests for Adults (30-49): Prostate cancer and Screening Tests for Adults (50 and Up): Prostate cancer.

Laboratory Testing
Laboratory testing may be used to detect prostate cancer, rule out other diseases and conditions that may be causing or worsening a person's symptoms, monitor the effectiveness of treatment for cancer, and monitor for recurrence.

Testing may include:

• PSA (total prostate specific antigen) – to detect and monitor prostate cancer; when evaluating test results, the healthcare practitioner must consider both the level of PSA in the blood and the volume of the man's prostate. (See Screening above and the PSA test page for discussion of variations of the PSA test.)
• Free PSA – PSA exists in two main forms in the blood: complexed (cPSA, bound to other proteins) and free (fPSA, not bound). The free PSA test may be used to help to determine whether a biopsy should be done when the total PSA is only slightly elevated. Men with BPH tend to have higher levels of free PSA and men with prostate cancer tend to have lower amounts of free PSA. A relatively low percentage of free PSA (% fPSA) increases the chances that a cancer is present, even if the total PSA is not significantly elevated.

Similar to free PSA, some other tests have been developed to aid some men and their healthcare practitioners in decisions about the whether to undergo biopsy when PSA is elevated. Biopsies used as a follow up to positive PSA results can cause discomfort, anxiety, and sometimes complications. These tests are relatively new:

• [-2] proPSA – this test looks for a precursor of PSA, which may be produced by prostate cancer cells at a higher rate than benign prostate cells. The percentage of [-2] proPSA relative to the total PSA level has been used, like the % fPSA, to help decide whether a biopsy is indicated.
• PCA3 – PCA3 is a protein produced only in the prostate gland. The test measures the urine level of PCA3 RNA.
• TMPRSS2-ERG gene fusion – this is a urine test that detects a gene rearrangement (a piece of chromosome breaks off and reattaches to another chromosome). The gene rearrangement is over-expressed in more than 50% of prostate cancers, so an elevated level may help to indicate that a prostate cancer is present.
• Prostate health index (phi) – this test combines results from total PSA, fPSA, and proPSA tests. The phi results can assess a man's chances of having prostate cancer and needing a biopsy when total PSA levels are elevated but the digital rectal examination is unremarkable.
• p2PSA – this test measures the levels of p2PSA, one of the forms of PSA that has similar functions. The level of p2PSA in the blood helps predict prostate cancer in men with elevated total PSA levels prior to biopsy. An elevated level increases the likelihood that the prostate cancer is aggressive. The accuracy of prostate cancer diagnosis is improved when p2PSA test results are combined with total and fPSA test results.

These tests do not provide a definitive answer as to whether a man has prostate cancer or not. Rather, they are intended to help predict whether a biopsy would be useful in helping to establish a diagnosis.

Diagnosis and Staging

The gold standard for diagnosing prostate cancer is the prostate biopsy, collecting small samples of prostate tissue and identifying abnormal cells under the microscope. If cancer is found, the healthcare practitioner will use the sample and imaging tests, such as an an MRI or CT scan, to determine the cancer's stage (how far it has spread into the body) and grade (how abnormal the cells appear). The cancer will be assigned a score, often called a Gleason score or Gleason grade. The higher the number, the more abnormal the tumor cells are and the more likely it is that the cancer will be aggressive and grow and spread quickly. For details, read Understanding Your Pathology Report: Prostate Cancer from the American Cancer Society.

General Lab Tests

Sometimes other tests may be done to rule out other conditions that cause similar symptoms:

• Urinalysis – to screen for kidney disorders and urinary tract infection (UTI)
• Urine culture – to help diagnose a UTI
• Blood urea nitrogen (BUN) and Creatinine – blood tests to evaluate kidney function

Non-laboratory tests may include:

• Ultrasound – a transrectal ultrasound (TRUS) may be used to help measure the size of the prostate and to help guide needle placement during a prostate biopsy
• CT (computed tomography) – to help evaluate the extent of the cancer
• MRI (magnetic resonance imaging) – to help evaluate the extent of the cancer
• Radionuclide bone scintigraphy – occasionally used to detect cancer that has spread to bone
• PET (positronic emission tomography) – occasionally used to help stage metastatic cancer (cancer that has spread beyond the prostate)
• Color Doppler ultrasound – measures blood flow within the prostate and may help make biopsies more accurate by identifying the right part of the gland to sample

By identifying the stage and grade of a prostate cancer, you and your healthcare practitioner can determine the most appropriate treatment options. In cases where the cancer is contained within the prostate, causing no or few symptoms, and appears to be slow-growing, you may decide to monitor its progress regularly rather than pursue immediate treatment. This may include "watchful waiting," which involves occasional PSA tests, or "active surveillance" that involves PSA tests done about every six months with digital rectal exams and prostate biopsies (annually) to monitor the cancer.

For those men with prostate cancer that requires medical intervention, some combination of surgery, radiation, and/or hormone therapy is usually used.

• Surgery, if elected, may remove the entire tumor or ease urination in more advanced cases. Cryosurgery, a relatively new surgical option, freezes and kills the affected tissue with liquid nitrogen.
• Radiation may be delivered with targeted rays from outside the body or with tiny radioactive seeds that are inserted into the prostate. Radiation can also be coupled with hormone therapy to provide pain relief in patients with prostate cancer that has spread to the bones.
• Hormone therapy is most commonly used to treat prostate cancer that has spread (metastasized) to other areas of the body. Male hormones called androgens stimulate prostate cancer cells to grow. Hormone therapy is used to lower the level of male hormones or to stop them from affecting prostate cancer cells. While it is not a cure at this stage, such therapy can shrink tumors, relieve symptoms, and extend the life of the affected man. Hormone therapy is also used to treat less advanced stages of prostate cancer, either in conjunction with radiation therapy or to shrink a tumor prior to surgery.
• Chemotherapy is rarely used for prostate cancer, but it may be used in advanced cases that are unresponsive to hormone therapy.

The side effects of different prostate cancer treatments can range from nonexistent to fatigue, hair loss, incontinence, and erectile dysfunction. Men with decreased testosterone levels due to treatment for prostate cancer may be at an increased risk for developing osteoporosis.

Prostate cancer detection and treatment options are continually improving and the recommendations of when and how to use these options are constantly evolving. Men should discuss current prostate cancer screening and treatment alternatives with their healthcare practitioners and make their own informed choices.