Disease: PSA Test
(Prostate Specific Antigen)

    Prostate specific antigen (PSA) facts

    • The PSA test is a blood test.
    • The PSA test can be used to suggest the presence of or monitor prostate cancer.
    • The PSA test can be abnormal with benign enlargement and infection of the prostate gland.
    • The PSA test can be elevated with other conditions that irritate the prostate gland.

    What is prostate specific antigen?

    Prostate specific antigen (PSA) is a substance produced almost exclusively by certain cells within the prostate gland. Biochemically, it belongs to the protease family of kallikrein and is also known as human kallikrein 3 (hK3). PSA is secreted by the prostate in the semen where its role is to liquefy the semen following ejaculation. Most of the PSA produced by the prostate gland is carried out of the body in semen, but a very small amount escapes into the blood stream, so PSA is normally found in low amounts (nanograms per milliliter or ng/mL) in the blood.

    If the PSA level is high for your age or is steadily increasing (with or without an abnormal physical exam), a biopsy may be recommended. The doctor should consider other risk factors of prostate cancer such as family history and ethnicity before recommending the biopsy. The biopsy is the only way to determine if prostate cancer or other abnormal cells are present in the prostate.

    How is PSA measured?

    PSA is measured by a blood test. Since the amount of PSA in the blood is very low, detection of it requires a very sensitive type of technology (monoclonal antibody technique). The PSA protein can exist in the blood by itself (known as free PSA), or bound with other substances (known as bound or complexed PSA). Total PSA is the sum of the free and the bound forms. The total PSA is what is measured with the standard PSA test.

    What causes PSA elevation in the blood?

    It is believed that elevation of PSA in the blood is due to its liberation into the circulation because of disruption of the prostate cellular architecture (structure). This can occur in the setting of different prostate diseases including prostate cancer. It is important to note that PSA is not specific to prostate cancer but to prostatic tissue and therefore PSA elevations may indicate the presence of any kind of prostate disease. The most common cause of PSA elevation includes benign prostatic hyperplasia (BPH = enlargement of the prostate, secondary to a noncancerous proliferation of prostate gland cells) and prostatitis (inflammation of the prostate). In fact, PSA elevation can also occur with prostate manipulation such as ejaculation, prostate examination, urinary retention or catheter placement, and prostate biopsy. As such, men choosing to undergo PSA testing should be aware of these important factors, which may influence results. Age and prostate volume may also influence PSA test results.

    What are normal results for the PSA test?

    The “normal” PSA serum concentration ranges between 1.0 and 4.0 ng/mL. However, since the prostate gland generally increases in size and produces more PSA with increasing age, it is normal to have lower levels in young men and higher levels in older men. The PSA level also depends on ethnicity and family history of prostate cancer. Other than the single reading, the changes in PSA numbers on an annual basis (also referred to as PSA-velocity) also play a role in decision making about the PSA marker. The normal increase of less than 0.75 ng/mL is used to help determine whether levels may be suggestive of disease and to counsel men on management. As such, a man under 50 to 59 years of age with an increase in PSA levels from 0.5 ng/mL to 2.5 ng/mL may cause greater concern despite the “normal” value at that time.

    What are age-specific reference ranges for serum PSA?

    The use of age-specific PSA ranges for the detection of prostate cancer is controversial. Not all studies have agreed that this is better than simply using a level of 4.0 ng/mL as the highest normal value. Nevertheless, due to the age-related growth of the prostate, the concept of adjusting the cutoff values based on age has helped reduce unnecessary prostate biopsies in older men to improve early prostate cancer detection. Below are the suggested age-adjusted values based on age and race.

    Age-Specific Reference Ranges for Serum PSA Age Range (Years) Asian Americans African Americans Caucasians 40 to 49 0 to 2.0 ng/mL 0 to 2.0 ng/mL 0 to 2.5 ng/mL 50 to 59 0 to 3.0 ng/mL 0 to 4.0 ng/mL 0 to 3.5 ng/mL 60 to 69 0 to 4.0 ng/mL 0 to 4.5 ng/mL 0 to 4.5 ng/mL 70 to 79 0 to 5.0 ng/mL 0 to 5.5 ng/mL 0 to 6.5 ng/mL

    How is PSA used for early detection prostate cancer?

    Clinically localized prostate cancer generally does not usually cause any clinical symptoms. Men usually feel perfectly well and prostate biopsy to detect prostate cancer is commonly initiated by an abnormal prostate digital rectal examination and/or an abnormal PSA value. It is for this reason that early detection tests have been developed in order to detect prostate cancer while it remains clinically silent and confined to the prostate. Hence, in clinical practice, tests used to detect prostate cancer include serum PSA level, digital rectal examination (DRE) and transrectal ultrasonography (TRUS).

    In particular, the level of PSA has been demonstrated to be an independent variable to predict the presence of prostate cancer. In fact, the higher the level, the more likely prostate cancer is present. An abnormal result will usually require additional testing. However, definitive diagnosis of prostate cancer depends on the presence of cancer cells obtained either from prostate biopsy or surgical specimens.

    In general, PSA levels greater than 4 ng/mL are usually considered suspicious. As levels increase above 10.0 ng/mL, the probability of cancer increases dramatically. However, not all men with prostate cancer have elevated PSA levels. It is known that a small but significant number of prostate cancers can present with a PSA level of less than 4.0 ng/mL. This is why doctors may use lower thresholds to decide when to do a biopsy.

    For an average man over the age of 50 with a normal digital rectal exam, the average probability of having prostate cancer detectable by prostate biopsy according to his PSA level is as follows:

    Probability of Prostate Cancer Detectable by Biopsy According to PSA Level PSA Level (ng/mL) 0 to 2.0 2.0 to 4.0 4.0 to 10.0 greater than 10.0 Prostate Cancer on Biopsy (%) 10% 25% 17% to 32% 43% to 65%

    Since the likelihood of having prostate cancer increases proportionately with PSA level, there is no threshold below which a man can be reassured that prostate cancer does not exist.

    In order to improve the specificity of the PSA test in the early detection of prostate cancer, several modifications of the serum PSA value have been described including the ratio of free/total PSA and the measurement of PSA change over time.

    What is the free PSA test?

    Most of the PSA protein released into the blood becomes attached to other blood proteins. The PSA that does not become attached is known as free PSA and can be measured. It has been found that the level of free PSA is decreased in men who have prostate cancer compared to those with benign conditions. The exact level depends upon which test the laboratory uses, but generally, a test result of less than 10% free PSA is suggestive of cancer. This test is most helpful when the usual PSA test level is between 4.0 ng/mL and 10.0 ng/mL.

    What is free/total PSA ratio?

    Although prostate cancer cells do not produce more PSA than benign prostate tissue, the PSA produced from cancerous cells appears to escape an enzymatic processing that cleaves the bond between PSA and its binding protein. Therefore, men with prostate cancer have a greater fraction of complexed, or bound, serum PSA and a lower percentage of total PSA that is free compared with men without prostate cancer. Therefore, the free/total PSA ratio can be used in clinical practice to discriminate between PSA elevation secondary to benign prostatic disease and prostate cancers. This is particularly useful for patients with a total PSA level between 4.0 and 10.0 ng/mL and a negative normal rectal exam to help the doctor to decide if a biopsy is necessary. In one study, prostate cancer was found in 56% of men with a free/total PSA less than 0.10 but in only 8% of men with free/total PSA greater than 0.25. Nevertheless, the concept of free PSA must be used with caution as several factors may influence the free/total PSA ratio such as temperature and prostate size. Furthermore, the free PSA measurement is not clinically useful for patients with total serum PSA values less than 10.0 ng/mL or in the follow-up of patients with known prostate cancer.

    What is PSA velocity and PSA doubling time?

    Change in PSA levels over time can be used to assess both cancer risk and aggressiveness of the particular tumor. PSA velocity is defined as an absolute annual increase in serum PSA (ng/mL/year). PSA doubling time is defined as the exponential increase of serum PSA over time and indicates a relative change. These two measures may have a prognostic role in patients that are being treated for prostate cancer. However, studies have shown that using values of these PSA measures for prostate cancer diagnosis do not provide additional information compared to PSA level alone.

    How is PSA testing used for pretreatment staging of prostate cancer?

    Once prostate cancer is diagnosed by the presence of cancer cells on prostate biopsy, PSA is used for cancer staging. Staging is used to decide what is the best management and appropriate treatment for the cancer. Serum PSA levels correlate with the risk of prostate cancer extension outside of the prostate including seminal vesicle invasion and lymph node involvement. The proportion of men with cancer confined to the prostate is about 80% when the PSA level at diagnosis is less than 4.0 ng/mL; about 70% when the PSA level is between 4.0 and 10.0 ng/mL; and about 50% when the PSA level is greater than 10.0 ng/mL. This is why patients with serum PSA levels of less than 10.0 ng/mL are most likely to respond well to local therapy such as prostatectomy (surgical removal of the prostate) or external beam radiation (radiation therapy). Over the past few decades, several predictive tools (otherwise called nomograms) have included the PSA in their parameters to predict posttreatment outcomes. These nomograms include the Partin and Kattan nomograms. For instance, the Kattan nomogram is an online predictive tool that is available to the public.

    How is PSA testing used in the management of prostate cancer posttreatment?

    A periodic PSA determination is used to detect disease recurrence after treatment. Serum PSA should decrease and remain at undetectable levels after local treatment such as radical prostatectomy. Following initial therapy, a PSA increase indicates recurrence of prostate cancer. For example, if the prostate gland is surgically removed, and all of the cancer is contained within the gland, then the PSA should drop to zero. Similarly, serum PSA should fall to a low level following radiation therapy, high intensity focused ultrasound, and cryotherapy.

    If on subsequent testing the PSA test is positive and shows increasing levels, it means that not all of the cancer was successfully removed and it is recurring. In addition, depending on the PSA level of the increase, it is possible that the cancer has now spread outside of the prostate.

    What are the limitations of the PSA test?

    The level of PSA is a continuous parameter; the higher the value, the higher the probability of having prostate cancer. On the other hand, men may have prostate cancer despite low levels of PSA. In a recent U.S. prevention study, 6.6% of the men whose PSA level was less than 0.5 ng/mL had prostate cancer. This is why there is no universally accepted cutoff at which we can be sure that there is no prostate cancer. Coupled with the lack of an accurate molecular marker to detect prostate cancer, the other controversy with PSA screening is the fact that not all men with prostate cancer will ever die from the disease (See: What is the PSA screening controversy?).

    For these reasons outlined above, it is important to not solely rely on blood PSA testing. The most useful additional test is a physical prostate examination by a doctor known as the digital rectal exam (DRE). Evidence from research studies suggests that the combination of both PSA and DRE improves the overall rate of prostate cancer detection. For that reason, men who would like to be screened for prostate cancer should have both a prostate specific antigen (PSA) test and a digital rectal examination (DRE).

    What is digital rectal examination (DRE)?

    Most prostate cancers are located in the peripheral zone of the prostate and may be detected by DRE. During this examination a doctor inserts a finger into the rectum to feel the prostate for lumps, size, shape, tenderness, and hardness. A suspect DRE is an absolute indication for prostate biopsy. In about 18% of patients with abnormal DRE, prostate cancer will be detected regardless of the PSA level.

    What is the PSA screening controversy?

    The goal of measuring PSA in men with no symptoms of cancer as a screening test for prostate cancer is to reduce the mortality caused by this cancer. However the usage of PSA as a screening tool for early detection of prostate cancer is subject to controversies over its ability to save lives.

    Widespread use of PSA screening came into practice particularly in North America driven by the assumption that detecting prostate cancers earlier will allow for earlier treatment and thereby decrease mortality caused by this disease.

    A substantial number of the cancers detected by PSA screening are low stage, and these patients will likely never die from this disease. PSA screening, due to its low specificity, does not allow differentiating between lethal and nonlethal types of cancers. Hence PSA systematic screening is inevitably associated with overdiagnosis and potentially overtreatment. Therefore, not only do these patients not benefit from early detection but they also carry the burden of a cancer diagnosis. In addition, a subset of these patients may suffer the side effects of an unnecessary treatment.

    Despite the inconvenience caused by overdiagnosis and overtreatment, one may argue that PSA screening can still be considered successful if overall, it improves disease-specific mortality in the population as a whole. Unfortunately, the conflicting results obtained from several randomized clinical trials specifically designed to evaluate the impact of PSA testing on prostate cancer mortality have not clarified the issue.

    One large European trial (ERSPC) found that PSA screening significantly reduces the mortality (death rate) of prostate cancer but is also associated with a high risk of overdiagnosis. The cumulative incidence of prostate cancer was 8.2% in the PSA screening group and 4.8% in the control group. Patients in the screening group were 20% less likely to die from prostate cancer compared with the control group. The absolute risk difference between the two groups was 0.71 deaths per 1,000 men. This means that to prevent one death from prostate cancer, 1,410 men would need to be screened with PSA testing and 48 additional cases of prostate cancer would need to be treated.

    Another trial (PLCO) conducted in the United States recently concluded that there is no evidence of an improvement in death rate from prostate cancer with annual PSA screening compared with usual medical care. After 13 years of follow-up, the cumulative mortality rates from prostate cancer in the intervention and control groups were 3.7 and 3.4 deaths per 10,000 person-years, respectively, meaning that there was significant difference between the two groups.

    Based on the results of the PLCO trial, the U.S. Preventive Service Task Force (USPSTF) advised against PSA screening in their draft recommendation issued in 2011. Nevertheless, many experts continue to believe that not using PSA screening would result in the deaths of many men with curable prostate cancer.

    Accordingly, although the effect of PSA screening on overdiagnosis and overtreatment of patients whose prostate cancer might not have resulted in death is of concern, early detection as opportunistic screening should still be offered. More than the overdiagnosis, the real challenge is to avoid overtreatment. Many patients with small, low-grade cancers may be candidates for active surveillance without treatment. This is why it is very important that men have an open and informed discussion with their doctor on the risks and benefits of prostate cancer screening before biopsy. In addition, the option of active surveillance instead of immediate treatment should always be discussed in case of newly diagnosed prostate cancer, if appropriate.

    Despite the controversy of several recent publications and task force recommendations, the American Urological Association (AUA) still recommends the use of PSA for early prostate cancer detection. Early detection and risk assessment should be offered to men 40 years of age or older who wish to be screened. The fundamental principle of the AUA position is that knowing a man's baseline PSA values in his 40s to compare with future PSA tests could help identify those men with life-threatening prostate cancer at a time when there are many treatment options and cure is possible.

    What causes PSA elevation in the blood?

    It is believed that elevation of PSA in the blood is due to its liberation into the circulation because of disruption of the prostate cellular architecture (structure). This can occur in the setting of different prostate diseases including prostate cancer. It is important to note that PSA is not specific to prostate cancer but to prostatic tissue and therefore PSA elevations may indicate the presence of any kind of prostate disease. The most common cause of PSA elevation includes benign prostatic hyperplasia (BPH = enlargement of the prostate, secondary to a noncancerous proliferation of prostate gland cells) and prostatitis (inflammation of the prostate). In fact, PSA elevation can also occur with prostate manipulation such as ejaculation, prostate examination, urinary retention or catheter placement, and prostate biopsy. As such, men choosing to undergo PSA testing should be aware of these important factors, which may influence results. Age and prostate volume may also influence PSA test results.

    What are normal results for the PSA test?

    The “normal” PSA serum concentration ranges between 1.0 and 4.0 ng/mL. However, since the prostate gland generally increases in size and produces more PSA with increasing age, it is normal to have lower levels in young men and higher levels in older men. The PSA level also depends on ethnicity and family history of prostate cancer. Other than the single reading, the changes in PSA numbers on an annual basis (also referred to as PSA-velocity) also play a role in decision making about the PSA marker. The normal increase of less than 0.75 ng/mL is used to help determine whether levels may be suggestive of disease and to counsel men on management. As such, a man under 50 to 59 years of age with an increase in PSA levels from 0.5 ng/mL to 2.5 ng/mL may cause greater concern despite the “normal” value at that time.

    What are age-specific reference ranges for serum PSA?

    The use of age-specific PSA ranges for the detection of prostate cancer is controversial. Not all studies have agreed that this is better than simply using a level of 4.0 ng/mL as the highest normal value. Nevertheless, due to the age-related growth of the prostate, the concept of adjusting the cutoff values based on age has helped reduce unnecessary prostate biopsies in older men to improve early prostate cancer detection. Below are the suggested age-adjusted values based on age and race.

    Age-Specific Reference Ranges for Serum PSA Age Range (Years) Asian Americans African Americans Caucasians 40 to 49 0 to 2.0 ng/mL 0 to 2.0 ng/mL 0 to 2.5 ng/mL 50 to 59 0 to 3.0 ng/mL 0 to 4.0 ng/mL 0 to 3.5 ng/mL 60 to 69 0 to 4.0 ng/mL 0 to 4.5 ng/mL 0 to 4.5 ng/mL 70 to 79 0 to 5.0 ng/mL 0 to 5.5 ng/mL 0 to 6.5 ng/mL

    How is PSA used for early detection prostate cancer?

    Clinically localized prostate cancer generally does not usually cause any clinical symptoms. Men usually feel perfectly well and prostate biopsy to detect prostate cancer is commonly initiated by an abnormal prostate digital rectal examination and/or an abnormal PSA value. It is for this reason that early detection tests have been developed in order to detect prostate cancer while it remains clinically silent and confined to the prostate. Hence, in clinical practice, tests used to detect prostate cancer include serum PSA level, digital rectal examination (DRE) and transrectal ultrasonography (TRUS).

    In particular, the level of PSA has been demonstrated to be an independent variable to predict the presence of prostate cancer. In fact, the higher the level, the more likely prostate cancer is present. An abnormal result will usually require additional testing. However, definitive diagnosis of prostate cancer depends on the presence of cancer cells obtained either from prostate biopsy or surgical specimens.

    In general, PSA levels greater than 4 ng/mL are usually considered suspicious. As levels increase above 10.0 ng/mL, the probability of cancer increases dramatically. However, not all men with prostate cancer have elevated PSA levels. It is known that a small but significant number of prostate cancers can present with a PSA level of less than 4.0 ng/mL. This is why doctors may use lower thresholds to decide when to do a biopsy.

    For an average man over the age of 50 with a normal digital rectal exam, the average probability of having prostate cancer detectable by prostate biopsy according to his PSA level is as follows:

    Probability of Prostate Cancer Detectable by Biopsy According to PSA Level PSA Level (ng/mL) 0 to 2.0 2.0 to 4.0 4.0 to 10.0 greater than 10.0 Prostate Cancer on Biopsy (%) 10% 25% 17% to 32% 43% to 65%

    Since the likelihood of having prostate cancer increases proportionately with PSA level, there is no threshold below which a man can be reassured that prostate cancer does not exist.

    In order to improve the specificity of the PSA test in the early detection of prostate cancer, several modifications of the serum PSA value have been described including the ratio of free/total PSA and the measurement of PSA change over time.

    What is the free PSA test?

    Most of the PSA protein released into the blood becomes attached to other blood proteins. The PSA that does not become attached is known as free PSA and can be measured. It has been found that the level of free PSA is decreased in men who have prostate cancer compared to those with benign conditions. The exact level depends upon which test the laboratory uses, but generally, a test result of less than 10% free PSA is suggestive of cancer. This test is most helpful when the usual PSA test level is between 4.0 ng/mL and 10.0 ng/mL.

    What is free/total PSA ratio?

    Although prostate cancer cells do not produce more PSA than benign prostate tissue, the PSA produced from cancerous cells appears to escape an enzymatic processing that cleaves the bond between PSA and its binding protein. Therefore, men with prostate cancer have a greater fraction of complexed, or bound, serum PSA and a lower percentage of total PSA that is free compared with men without prostate cancer. Therefore, the free/total PSA ratio can be used in clinical practice to discriminate between PSA elevation secondary to benign prostatic disease and prostate cancers. This is particularly useful for patients with a total PSA level between 4.0 and 10.0 ng/mL and a negative normal rectal exam to help the doctor to decide if a biopsy is necessary. In one study, prostate cancer was found in 56% of men with a free/total PSA less than 0.10 but in only 8% of men with free/total PSA greater than 0.25. Nevertheless, the concept of free PSA must be used with caution as several factors may influence the free/total PSA ratio such as temperature and prostate size. Furthermore, the free PSA measurement is not clinically useful for patients with total serum PSA values less than 10.0 ng/mL or in the follow-up of patients with known prostate cancer.

    What is PSA velocity and PSA doubling time?

    Change in PSA levels over time can be used to assess both cancer risk and aggressiveness of the particular tumor. PSA velocity is defined as an absolute annual increase in serum PSA (ng/mL/year). PSA doubling time is defined as the exponential increase of serum PSA over time and indicates a relative change. These two measures may have a prognostic role in patients that are being treated for prostate cancer. However, studies have shown that using values of these PSA measures for prostate cancer diagnosis do not provide additional information compared to PSA level alone.

    How is PSA testing used for pretreatment staging of prostate cancer?

    Once prostate cancer is diagnosed by the presence of cancer cells on prostate biopsy, PSA is used for cancer staging. Staging is used to decide what is the best management and appropriate treatment for the cancer. Serum PSA levels correlate with the risk of prostate cancer extension outside of the prostate including seminal vesicle invasion and lymph node involvement. The proportion of men with cancer confined to the prostate is about 80% when the PSA level at diagnosis is less than 4.0 ng/mL; about 70% when the PSA level is between 4.0 and 10.0 ng/mL; and about 50% when the PSA level is greater than 10.0 ng/mL. This is why patients with serum PSA levels of less than 10.0 ng/mL are most likely to respond well to local therapy such as prostatectomy (surgical removal of the prostate) or external beam radiation (radiation therapy). Over the past few decades, several predictive tools (otherwise called nomograms) have included the PSA in their parameters to predict posttreatment outcomes. These nomograms include the Partin and Kattan nomograms. For instance, the Kattan nomogram is an online predictive tool that is available to the public.

    How is PSA testing used in the management of prostate cancer posttreatment?

    A periodic PSA determination is used to detect disease recurrence after treatment. Serum PSA should decrease and remain at undetectable levels after local treatment such as radical prostatectomy. Following initial therapy, a PSA increase indicates recurrence of prostate cancer. For example, if the prostate gland is surgically removed, and all of the cancer is contained within the gland, then the PSA should drop to zero. Similarly, serum PSA should fall to a low level following radiation therapy, high intensity focused ultrasound, and cryotherapy.

    If on subsequent testing the PSA test is positive and shows increasing levels, it means that not all of the cancer was successfully removed and it is recurring. In addition, depending on the PSA level of the increase, it is possible that the cancer has now spread outside of the prostate.

    What are the limitations of the PSA test?

    The level of PSA is a continuous parameter; the higher the value, the higher the probability of having prostate cancer. On the other hand, men may have prostate cancer despite low levels of PSA. In a recent U.S. prevention study, 6.6% of the men whose PSA level was less than 0.5 ng/mL had prostate cancer. This is why there is no universally accepted cutoff at which we can be sure that there is no prostate cancer. Coupled with the lack of an accurate molecular marker to detect prostate cancer, the other controversy with PSA screening is the fact that not all men with prostate cancer will ever die from the disease (See: What is the PSA screening controversy?).

    For these reasons outlined above, it is important to not solely rely on blood PSA testing. The most useful additional test is a physical prostate examination by a doctor known as the digital rectal exam (DRE). Evidence from research studies suggests that the combination of both PSA and DRE improves the overall rate of prostate cancer detection. For that reason, men who would like to be screened for prostate cancer should have both a prostate specific antigen (PSA) test and a digital rectal examination (DRE).

    What is digital rectal examination (DRE)?

    Most prostate cancers are located in the peripheral zone of the prostate and may be detected by DRE. During this examination a doctor inserts a finger into the rectum to feel the prostate for lumps, size, shape, tenderness, and hardness. A suspect DRE is an absolute indication for prostate biopsy. In about 18% of patients with abnormal DRE, prostate cancer will be detected regardless of the PSA level.

    What is the PSA screening controversy?

    The goal of measuring PSA in men with no symptoms of cancer as a screening test for prostate cancer is to reduce the mortality caused by this cancer. However the usage of PSA as a screening tool for early detection of prostate cancer is subject to controversies over its ability to save lives.

    Widespread use of PSA screening came into practice particularly in North America driven by the assumption that detecting prostate cancers earlier will allow for earlier treatment and thereby decrease mortality caused by this disease.

    A substantial number of the cancers detected by PSA screening are low stage, and these patients will likely never die from this disease. PSA screening, due to its low specificity, does not allow differentiating between lethal and nonlethal types of cancers. Hence PSA systematic screening is inevitably associated with overdiagnosis and potentially overtreatment. Therefore, not only do these patients not benefit from early detection but they also carry the burden of a cancer diagnosis. In addition, a subset of these patients may suffer the side effects of an unnecessary treatment.

    Despite the inconvenience caused by overdiagnosis and overtreatment, one may argue that PSA screening can still be considered successful if overall, it improves disease-specific mortality in the population as a whole. Unfortunately, the conflicting results obtained from several randomized clinical trials specifically designed to evaluate the impact of PSA testing on prostate cancer mortality have not clarified the issue.

    One large European trial (ERSPC) found that PSA screening significantly reduces the mortality (death rate) of prostate cancer but is also associated with a high risk of overdiagnosis. The cumulative incidence of prostate cancer was 8.2% in the PSA screening group and 4.8% in the control group. Patients in the screening group were 20% less likely to die from prostate cancer compared with the control group. The absolute risk difference between the two groups was 0.71 deaths per 1,000 men. This means that to prevent one death from prostate cancer, 1,410 men would need to be screened with PSA testing and 48 additional cases of prostate cancer would need to be treated.

    Another trial (PLCO) conducted in the United States recently concluded that there is no evidence of an improvement in death rate from prostate cancer with annual PSA screening compared with usual medical care. After 13 years of follow-up, the cumulative mortality rates from prostate cancer in the intervention and control groups were 3.7 and 3.4 deaths per 10,000 person-years, respectively, meaning that there was significant difference between the two groups.

    Based on the results of the PLCO trial, the U.S. Preventive Service Task Force (USPSTF) advised against PSA screening in their draft recommendation issued in 2011. Nevertheless, many experts continue to believe that not using PSA screening would result in the deaths of many men with curable prostate cancer.

    Accordingly, although the effect of PSA screening on overdiagnosis and overtreatment of patients whose prostate cancer might not have resulted in death is of concern, early detection as opportunistic screening should still be offered. More than the overdiagnosis, the real challenge is to avoid overtreatment. Many patients with small, low-grade cancers may be candidates for active surveillance without treatment. This is why it is very important that men have an open and informed discussion with their doctor on the risks and benefits of prostate cancer screening before biopsy. In addition, the option of active surveillance instead of immediate treatment should always be discussed in case of newly diagnosed prostate cancer, if appropriate.

    Despite the controversy of several recent publications and task force recommendations, the American Urological Association (AUA) still recommends the use of PSA for early prostate cancer detection. Early detection and risk assessment should be offered to men 40 years of age or older who wish to be screened. The fundamental principle of the AUA position is that knowing a man's baseline PSA values in his 40s to compare with future PSA tests could help identify those men with life-threatening prostate cancer at a time when there are many treatment options and cure is possible.

    Source: http://www.rxlist.com

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