PSA velocity - Prostate Cancer detection

[buckminster]

Medicine is ever changing area that is why it an art of science. Recenlty PSA velocity is gaining much of hype in the news media because of its relation with the Prostate Cancer.

PSA is a protein molecule made by prostate gland cells. Its function is to liquefy the stored seminal coagulum and thus enhance the motility of the sperm cells to aid fertilization. The protein also prevents sperm cells clumping together. PSA stands for prostatic specific antigen. This does not mean it is an antigen in the sense that it can attack you. It refers to the fact that an antibody was developed that could recognise it and attach to it. For all intents and purposes PSA is made only by the prostate gland hence the word specific. However it is known that really tint quantities in the blood do originate in other glands of the body.

Very small amounts of the PSA protein leak out of the gland into the blood stream from the prostate gland cells that make the PSA. Therefore all men will have detectable levels of PSA in their bloodstreams unless they have a congenital absence of the prostate gland or the gland has been removed.

There is a so-called normal level of PSA in the blood. It should be less than four nanograms per millilitre. However this time honoured value really is fairly meaningless and one should not believe that there is a cancer present if the PSA is higher than 4 ng/ml nor should one feel a cancer cannot be present if the PSA is less than 4 ng/ml. in the USA, the trend has moved to investigating men with a PSA of over 2,6 ng/ml.

PSA comes in different varieties. The two commonest forms of PSA are called free PSA and complexed PSA. Free PSA floats around in the blood stream on its own whilst complexed PSA is bound to a protein carrier molecule in the blood. The total PSA is the sum of these two types of PSA. The less common varieties of PSA can be ignored in the total because they contribute less than 1% of the total sum. There is a so called normal ratio of free PSA and complexed PSA such that there should be 1 part free PSA to 3 parts complexed PSA or free PSA should be around 25% of the total.

If the ratio of free to complexed PSA changes in that there is relatively more complexed PSA or less free PSA making up the total then this could indicate that a tumour is present. Early cancers resemble normal cells very closely. Also they function in most respects like a normal cell and as such these cells make PSA as well. A major difference between a normal cell and a cancer cell is that cancer cell walls tend to be more leaky and PSA, particularly complexed PSA, is lost more readily into the blood stream. This explains why the PSA can rise when a cancer is present and also why the complexed PSA can increase in relation to the free PSA when a cancer is present.

Prostate glands in the majority of men tend to enlarge as men age. This is because there are new prostate cells being made all the time but very few if any are dieing. Because there are more cells making PSA, this means that the level of PSA will gradually rise in men as they grow older. There is therefore a concept known as age related PSA value. The urologist will take this into account when he assesses you for a possible cancer. A man of 70 years can have a PSA of 6 and be comfortable with this level however a man of 40 years should have a PSA of less than 2,5 ng/ml.

Because of the gradual increase in size of the prostate gland, PSA will therefore rise slightly on an annual basis. This annual rate of rise is called PSA velocity. PSA velocity is concept that is no longer in vogue. It used to be said that the PSA should not rise by more than 0,75 ng/ml/year. Experience with PSA has shown this concept to be of little use in monitoring for cancer development. However when a cancer is suspected; and there is a persistent and significant increase in the PSA, then the patient and the urologist will need to be more vigilant in searching for a developing cancer.

Another tool is to check the PSA doubling time. This is the time taken for the PSA level to double. A doubling time of several years is much less worrying than one of several months.

Cancer is not the only cause of a raised PSA. As mentioned previously prostate size affects the gland. Benign enlargement or BPH, of the prostate gland is a very common condition of the ageing male. It is far more common than cancer in terms of its clinical impact. Only around 10% of men will develop a clinical prostate cancer in their life times yet at least forty percent of men will suffer from symptoms related to a prostate causing obstruction to the bladder. BPH does not turn into a cancer. This is a common belief among the public and even some medical practitioners.

Secondly inflammation of the prostate gland called prostatitis will cause the PSA to rise. Acute inflammation can cause the PSA to rise several fold. Even following treatment the PSA may take several weeks to return to a baseline level. Chronic inflammation is a common condition that may or may not produce symptoms. It can cause the PSA to increase as well but usually the increase is small but persistent. It is important to treat prostatitis before making any judgement call on the PSA level. It should be noted that prostatitis can be very difficult to treat because antibiotics find it very difficult to penetrate the prostate gland. Furthermore there are other more common conditions of prostatitis than bacterial infection and in these cases antibiotics will have no affect anyway.

Several factors can affect the PSA level that have nothing to do with disease. These factors are important to note before you have a PSA test.

Firstly the laboratory used should always be the same. Different labs use different techniques to measure PSA and thus there can be significant differences in the results of the same blood tested by different labs. Furthermore the lab conditions vary from day to day and it would be unusual for any one lab to be able to meet a consistency of greater than 80% in their testing methods.

PSA should be taken prior to any digital rectal examination. However this is not always practical. The doctor who exams you, if diligent will include a digital rectal examination in his repertoire of clinical tests. The presence of an abnormality will then direct him or her to ask for a PSA test. The rectal exam can raise the PSA by 10%. This can be taken into account by the examining doctor but for patients who have a deep seated interest in monitoring their PSA accurately this can be irritating and possibly lead to unnecessary worry. The wisest course is to ask for a PSA test before any rectal examination.

The prostate gland lies very close to the perineal area. This is the part of your body that is in contact with a saddle on a bicycle or motor bike or a horse. The jarring of the saddle against the perineal region can cause the PSA to rise. Therefore before a PSA test these activities should not be undertaken for about a week.

Sexual intercourse can also cause the PSA to rise for up to two days. On should thus be celibate for two days prior to the test.

Alcohol and coffee may have an affect on PSA and so these beverages should be avoided prior to the PSA test. Lastly never accept the so called normal PSA level as meaning you cannot have a cancer. Beware the doctor who will base the presence or absence of a cancer purely on a PSA result. That is bad medical practise.

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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.

[buckminster]

Prostate cancer can often be found early by testing the amount of prostate-specific antigen (PSA), discussed in detail below, in your blood. Prostate cancer may also be found on a digital rectal exam (DRE), in which your doctor inserts a gloved finger into the rectum. Because your prostate gland lies just in front of your rectum, the doctor can feel whether there are any bumps or hard areas in your prostate. If there are, you will need further testing to see if there is a cancer. If you have routine yearly exams and either one of these test results becomes abnormal, then any cancer you might have has likely been found at an early, more treatable stage.

Since the use of early detection tests for prostate cancer became fairly common (about 1990), the prostate cancer death rate has dropped. But it has not been proven that this is a direct result of screening.

There are limits to the current screening methods. Neither the PSA test nor the DRE is 100% accurate. Uncertain or false test results could cause confusion and anxiety. Some men might have a prostate biopsy (which carries its own small risks, along with discomfort) when cancer is not present, while others might get a false sense of security from normal test results when cancer is actually present.

There is no question that the PSA test can help spot many prostate cancers early, but another important issue is that it can't tell how dangerous the cancer is. Finding and treating all prostate cancers early may seem like a no-brainer. But some prostate cancers grow so slowly that they would likely never cause problems. Because of an elevated PSA level, some men may be diagnosed with a prostate cancer that would never have caused any symptoms or lead to their death. But they may still be treated with either surgery or radiation, either because the doctor can't be sure how aggressive the cancer might be, or because the men are uncomfortable not having any treatment. These treatments can have side effects that seriously affect a man's quality of life. Doctors and patients are still struggling to decide who should receive treatment and who might be able to be followed without being treated right away (an approach called "watchful waiting" or “expectant management”).

Until more information is available, whether you have the tests is something for you and your doctor to decide. There are many factors to take into account, including your age and health. If you are young and develop prostate cancer, it will probably shorten your life if it is not caught early. If you are older or in poor health, then prostate cancer may never become a major problem because it is generally a slow-growing cancer.

ACS Recommendations for the Early Detection of Prostate Cancer

The American Cancer Society believes that health care professionals should offer the prostate-specific antigen (PSA) blood test and digital rectal exam (DRE) yearly, beginning at age 50, to men who have at least a 10-year life expectancy. Men at high risk, such as African Americans and men who have a first-degree relative (father, brother, or son) diagnosed with prostate cancer at an early age (younger than age 65), should begin testing at age 45.

Men at even higher risk (because they have several first-degree relatives who had prostate cancer at an early age) could begin testing at age 40. Depending on the results of this initial test, further testing might not be needed until age 45.

Health care professionals should give men the chance to openly discuss the benefits and limitations of testing at yearly checkups. Men should actively take part in the decision by learning about prostate cancer and the pros and cons of early detection and treatment of prostate cancer.

Recommendations of Other Organizations


No major scientific or medical organizations, including the American Cancer Society (ACS), American Urological Association (AUA), US Preventive Services Task Force (USPSTF), American College of Physicians (ACP), National Cancer Institute (NCI), American Academy of Family Physicians (AAFP), and American College of Preventive Medicine (ACPM) support routine testing for prostate cancer at this time. The USPSTF has concluded that studies completed so far do not provide enough evidence to know whether the benefits of testing for early prostate cancer outweigh the possible risks.

The ACS, AUA, ACP, NCI, AAFP, and ACPM recommend that health care professionals discuss the possible benefits, side effects, and questions about early prostate cancer detection and treatment so that men can make informed decisions taking into account their own situation and risk. In addition, the American Cancer Society and the American Urological Association recommend that health care professionals offer the option of testing for early detection of prostate cancer to all men who are at least 50 years old (or younger if at higher risk).

Prostate-Specific Antigen (PSA) Blood Test

Prostate-specific antigen (PSA) is a substance made by cells in prostate gland (whether they are normal or cancerous). Although PSA is mostly found in semen, a small amount is also found in the blood. Most men have levels under 4 nanograms per milliliter (ng/mL) of blood.

When prostate cancer develops, the PSA level usually goes above 4. But about 15% of men with a PSA below 4 will have prostate cancer on biopsy. If your PSA level is in the borderline range between 4 and 10, you have about a 1 in 4 chance of having prostate cancer. If it is more than 10, your chance of having prostate cancer is over 50% and increases more as your PSA level increases. The PSA level can also be affected by a number of factors other than prostate cancer:

• It rises with non-cancerous enlargement of the prostate (called benign prostatic hyperplasia, or BPH), something many men have as they grow older.
• It can also increase with prostatitis, an infection or inflammation of the prostate gland.
• Your PSA will also normally go up slowly as you age, even if you have no prostate abnormality.
• Ejaculation can cause a temporary increase in blood PSA levels, so some doctors will suggest that men abstain from ejaculation for 2 days before testing.
• Some medicines used to treat BPH or urinary symptoms may affect blood PSA levels. You should tell your doctor if you are taking finasteride (Proscar or Propecia) or dutasteride (Avodart), as these medicines may falsely lower PSA levels and require the doctor to adjust the reading.
• Herbal mixtures that are sold as dietary supplements "for prostate health" may affect PSA levels. For example, they could mask a high PSA level. This is why it is important to let your doctor know if you are taking any type of supplement. Saw palmetto (an herb used by some men to treat BPH) does not seem to interfere with the measurement of PSA.

If your PSA level is high, your doctor may advise a prostate biopsy to find out if you have cancer. Some doctors may consider using newer types of PSA tests (discussed below) to help determine if you need a prostate biopsy, but not all doctors agree on how to use these other PSA tests. If your PSA test result is not normal, ask your doctor to discuss your cancer risk and your need for further tests.

Percent-free PSA

PSA occurs in 2 major forms in the blood. One form is attached to blood proteins while the other circulates free (unattached). The percent-free PSA (fPSA) is the ratio of how much PSA circulates free compared to the total PSA level. The percentage of free PSA is lower in men who have prostate cancer than in men who do not.

This test is sometimes used to help decide if you should have a prostate biopsy if your PSA results are in the borderline range (4-10 ng/mL). A lower percent-free PSA means that your likelihood of having prostate cancer is higher and you should probably have a biopsy. Many doctors recommend biopsies for men whose percent-free PSA is 10% or less, and advise that men consider a biopsy if it is between 10% and 25%. Using these cutoffs detects most cancers while helping some men to avoid unnecessary prostate biopsies. Although this test is widely used, not all doctors agree that 25% is the best "cutoff point" to decide on a biopsy.

A newer test, known as complexed PSA, measures the amount of PSA that is attached to other proteins. This test is described in more detail in the section, "What's New in Prostate Cancer Research and Treatment?"

PSA Velocity

The PSA velocity is not a separate test. It is a measure of how fast the PSA rises over time. Even when the total PSA value isn't over 4 ng/mL, a high PSA velocity suggests that cancer may be present and a biopsy should be considered. For example, if your PSA was 1.7 on one test, and then a year later it was 3.8, this rapid rise may be cause for concern.

This can be useful if you are having the PSA test every year. For men whose initial PSA value is less than 4, a PSA velocity of 0.35 ng/mL per year or greater (for example, if values went from 2 to 2.4 to 2.8 over the course of 2 years) may be cause for concern. For men whose PSA value is between 4 and 10, a biopsy should be more strongly considered if it goes up faster than 0.75 ng/mL per year (for example, if values went from 4 to 4.8 to 5.6 over the course of 2 years). Most doctors believe that PSA levels should be measured on at least 3 occasions over a period of at least 18 months in order to get an accurate PSA velocity.

PSA Density

PSA levels are higher in men with larger prostate glands. The PSA density (PSAD) is sometimes used for men with large prostate glands to try to adjust for this. The doctor measures the volume (size) of the prostate gland with transrectal ultrasound (discussed below) and divides the PSA number by the prostate volume. A higher PSA density (PSAD) indicates greater likelihood of cancer. PSA density has not been shown to be that useful. The percent-free PSA test has so far been shown to be more accurate.

Age-specific PSA Ranges

A PSA result within the borderline range might be very worrisome in a 50-year-old man but cause less concern in an 80-year-old man. It is known that PSA levels are normally higher in older men than in younger men, even when there is no cancer. For this reason, some doctors have suggested comparing PSA results with results from other men of the same age.

But because the usefulness of age-specific PSA ranges is not well proven, most doctors and professional organizations (as well as the makers of the PSA tests) do not recommend their use at this time.

Use of the PSA Blood Test After Prostate Cancer Diagnosis

Although the PSA test is used mainly to detect prostate cancer early, it is useful in other situations:

• In men diagnosed with prostate cancer, the PSA test can be used together with clinical exam results and tumor grade (from the biopsy) to help decide if further tests (such as CT scans or bone scans) are needed.
• It can help tell whether your cancer is still confined to the prostate gland. If your PSA level is very high, your cancer has likely spread beyond the prostate. This may affect your treatment options, since some forms of therapy (such as surgery and radiation) are not likely to be helpful if the cancer has spread to the lymph nodes, bones, or other organs.
• After surgery or radiation treatment, the PSA level can be watched to help determine if the treatment was successful. PSA levels normally fall to very low levels if the treatment removed or destroyed all of the prostate cells. A rising PSA level (especially after surgery) likely means that prostate cancer cells are present and your cancer has come back.
• If you choose a "watchful waiting" approach to treatment, the PSA level can be used to help decide whether the cancer is growing and if active treatment should be considered.
• During hormonal therapy or chemotherapy, the PSA level can help indicate how well the treatment is working or when it may be time to try a different form of treatment.

If prostate cancer has come back (recurred) after treatment, or if it has spread outside of the prostate (metastatic disease), the actual PSA number is probably not as important as whether it changes. The PSA number does not predict whether or not a person will have symptoms or how long he will live. Many people have very high PSA values and feel just fine. Other people have low values and have symptoms. With advanced disease, it may be more important to look at the way the PSA level is changing rather than the actual number.

Digital Rectal Exam (DRE)

During this exam, a doctor inserts a gloved, lubricated finger into the rectum to feel for any bumps or hard areas that might be a cancer. The prostate gland is found just in front of the rectum, and most cancers begin in the back part of the gland, which can be felt during a rectal exam. While it is uncomfortable, the exam causes no pain and only takes a short time.

Although DRE is less effective than the PSA blood test in finding prostate cancer, it can sometimes find cancers in men with normal PSA levels. For this reason, the American Cancer Society guidelines recommend that when prostate cancer screening is done, both the DRE and PSA blood test should be used.

The DRE can also be used once a man is known to have prostate cancer to try to determine if it may have spread to nearby tissues and to detect cancer that has come back after treatment.

Transrectal Ultrasound (TRUS)

Transrectal ultrasound (TRUS) uses sound waves to make an image of the prostate on a video screen. For this test, a small probe is placed in the rectum. It gives off sound waves, which enter the prostate and create echoes that are picked up by the probe. A computer turns the pattern of echoes into a black and white image of the prostate.

The procedure takes only a few minutes and is done in a doctor's office or outpatient clinic. You will feel some pressure when the TRUS probe is placed in your rectum, but it is usually not painful.

TRUS is usually not recommended as a routine test by itself to detect prostate cancer because it doesn't often show early cancer. Instead, it is most commonly used during a prostate biopsy (described in the next section). TRUS is used to guide the biopsy needles into the right area of the prostate.

TRUS is useful in other situations as well. It can be used to measure the size of the prostate gland, which can help determine the PSA density and may also affect which treatment options a man has. It is also used as a guide during some forms of treatment such as cryosurgery.

Signs and Symptoms of Prostate Cancer

Early prostate cancer usually causes no symptoms and is most often found by a PSA test and/or DRE. Some advanced prostate cancers can slow or weaken your urinary stream or make you need to urinate more often. But non-cancerous diseases of the prostate, such as BPH (benign prostatic hyperplasia) cause these symptoms more often.

If the prostate cancer is advanced, you might have blood in your urine (hematuria) or trouble getting an erection (impotence). Advanced prostate cancer commonly spreads to the bones, which can cause pain in the hips, spine, ribs, or other areas. Cancer that has spread to the spine can also press on the spinal nerves, which can result in weakness or numbness in the legs or feet, or even loss of bladder or bowel control.

Other diseases, however, can also cause many of these same symptoms. It is important to tell your doctor if you have any of these problems so that the cause can be found and treated.