Prostate Cancer

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 prostatitis, 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 providers must determine whether a man's symptoms are due to prostate cancer, BPH, or to another non-cancer-related condition. This may involve a PSA test 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 providers, whether to undergo screening for prostate cancer. Many organizations, such as the American Cancer Society and the American Urological Association, recommend that men discuss the advantages and disadvantages of PSA-based screening for prostate cancer with their healthcare provider before making an informed decision about whether to be screened or not, However, some organizations, such as the U.S. Preventive Services Task Force, feel that the harms associated with over-diagnosis and over-treatment outweigh the potential benefits and advise against using PSA to screen for prostate cancer in healthy men of any age.

One important factor to consider when deciding whether to undergo screening is 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
• High risk—includes men with more than one relative who was affected at a young age

For men who wish to be screened for prostate cancer, the American Cancer Society recommends that healthy men of average risk consider waiting to get tested until age 50, while the American Urological Association recommends screening for men between the ages of 55 and 69 with no routine screening after age 70.

For those at high risk, such as American men of African descent and men with a family history of the disease, the recommendation is to consider beginning testing at age 40 or 45.

While elevated PSA levels are associated with cancer, they may be caused by other conditions, such as BPH and inflammation of the prostate. Since a PSA test can be elevated temporarily for a variety of reasons, a repeat PSA may be done a few weeks after an initially elevated one to determine if it is still elevated. If the repeat test is elevated, a healthcare provider may recommend that series of PSAs be done over time to determine whether the level goes down, stays elevated, or continues to increase.

An elevated PSA may be followed by a biopsy, which has risk of complications such as pain, fever, blood in the urine, or urinary tract infection. (Read the article on Anatomic Pathology for more information about biopsies.) If prostate cancer is diagnosed, it must also be determined whether it is clinically significant. If a prostate cancer is small, localized, and slow-growing, it may never cause significant health problems.

There is a saying that "many men die with prostate cancer, not from it." In these cases, the treatments may sometimes be worse than the cancer as they can cause side effects such as erectile dysfunction and incontinence. In cases where the cancer appears to be slow-growing, the healthcare provider and patient may decide to monitor its progress rather than pursue immediate treatment (called "watchful waiting").

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 enough and troublesome enough that they require medical intervention. The challenge is to detect prostate cancer, evaluate its growth rate and spread, and for the patient and his healthcare provider to decide which treatment courses to follow and when.

Laboratory Testing
Laboratory testing may be used to screen asymptomatic and symptomatic men for 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 help screen for and monitor prostate cancer. PSA is a good but not perfect tool. Some organizations, such as the U.S. Preventive Services Task Force, feel that the harms associated with over-diagnosis and over-treatment outweigh the potential benefits and advise against using PSA to screen for prostate cancer in healthy men of any age. The American Cancer Society, American Urological Association, and American College of Physicians recommend that men discuss the advantages and disadvantages of PSA-based screening for prostate cancer with their healthcare provider before making an informed decision about whether to be screened or not. (See Screening Tests for Adults (30-49): Prostate cancer and Screening Tests for Adults (50 and Up): Prostate cancer for details on screening recommendations.). Increased levels of total PSA have been associated with an increased risk of prostate cancer but are also found with BPH, prostatitis, infection, and a variety of other temporary conditions. When evaluating the results, the healthcare provider must consider both the level of PSA in the blood and the volume of the man's prostate. (See the PSA test page for discussion of variations of the PSA test.)
• The digital rectal exam (DRE) is a physical examination. To perform the DRE, a health practitioner inserts a gloved, lubricated finger into the rectum and feels the prostate gland with his finger to detect abnormalities. 
• Free PSA – PSA exists in two main forms in the blood: complexed (cPSA, bound to other proteins) and free (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 level of free PSA 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 providers in decisions about the whether to undergo biopsy. Biopsies used in follow up to positive PSA results can cause discomfort, anxiety, and sometimes complications. These tests are relatively new and not yet widely available:

• [-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 % free PSA, 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 messenger RNA (m-RNA), a signal from genes that tells the prostate to produce the PCA3 protein. Increased amounts of the m-RNA (over-expressed) are produced by 95% of prostate cancer cells, so an elevated level may help to indicate that a prostate cancer is present.
• TMPRSS2-ERG gene fusion – this test is also a urine-based assay. It detects mRNA that is the result of a gene rearrangement. 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.

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

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 health practitioner will use the sample and imaging tests, such as an ultrasound, to determine the cancer's stage (how far it has spread into the body) and grade (how abnormal the cells appear). The more abnormal the tumor cells are, the more likely it is that the cancer will be aggressive.

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)

By identifying the stage and grade of a prostate cancer, the healthcare provider and affected man 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, they may decide to monitor its progress regularly rather than pursue immediate treatment. This is called "watchful waiting," and it is a strategy that may work well for many years.

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 metastasized to other areas of the body. While it is not a cure at this stage, such therapy can shrink tumors, relieve symptoms, and extend the life of the affected mean. 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 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 providers and make their own informed choices.