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  Screening for Prostate Cancer


The controversy about prostate cancer screening is based on the fact that 60-80% of men may have prostate cancer cells in their gland but only 16% will be diagnosed and only 3% of men will die of prostate cancer. The ACS (American Cancer Society) recommends that the prostate specific antigen test (PSA) and digital rectal examination (DRE) should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk, including men of African descent   and men with a first-degree relative diagnosed at a younger age should begin testing at age 45. In 2010 they updated their advice on screening (go here).

Men at even higher risk of prostate cancer due to multiple first-degree relatives diagnosed with prostate cancer at an early age could begin testing at age 40. However, if PSA is less than 1.0 ng/ml, no additional testing is needed until age 45. If PSA is greater than 1.0 ng/ml but less than 2.5 ng/ml, annual testing is recommended. If PSA is 2.5 ng/ml or greater, further evaluation with biopsy should be considered, or if the PSA rises more than 0.35 per year (consider either a biopsy or check a free-PSA). Even men with a 'normal PSA' may have cancer, see study here. Recent review on prostate cancer screening here.

Go here for screening information, NCI screening, and NCCN screen.

The reason PSA screening remains controversial is the fact that as many as 80% of old men may have some prostate cancer cells in their gland but only 3% of men die from prostate cancer. So the question is whether diagnosing cancer in all of these men is really beneficial. A recent major American study showed no survival benefit from screening (go here) but a large European study showed the opposite (i.e. screening lowered the risk of dying of prostate cancer by 20%, see here). Another study showed an apparent survival benefit from screen ( go here)

As noted above even a PSA over 2.5 may be cause for a biopsy (not 4.0 as commonly thought) see editorial  below:

Verification Bias and the Prostate-Specific Antigen Test — Is There a Case for a Lower Threshold for Biopsy?
Fritz H. Schröder, M.D., Ph.D., and Ries Kranse, Ph.D. NEJM 2003349:393
Punglia  used a logistic-regression model that included all available variables that can affect the diagnosis of prostate cancer. The information obtained by this analysis of the 705 men who underwent a prostate biopsy was used to assess the probability of detecting prostate cancer by means of a biopsy in all 6691 men in the cohort. These probabilities were then used to calculate the sensitivity and specificity of specific threshold PSA values.The differences between the uncorrected and corrected PSA results were considerable, especially for younger men. Punglia et al. found that if biopsies were performed only when the PSA value was higher than 4.0 ng per milliliter, 82 percent of cancers would be missed in men who were younger than 60 years of age, and 65 percent would be missed in those who were 60 or older. Should we further decrease the PSA threshold and the age at which a prostate biopsy is recommended, as Punglia et al. suggest?

These findings are difficult to apply clinically. Clinicians want absolute numbers that show the effect of lower PSA cutoff points with respect to the detection rate, number of cancers missed, and number of cases requiring a biopsy if all cancers that could be detected by biopsy were diagnosed. Such data have been obtained in a study of a consecutive sample of 8621 men between the ages of 55 and 74 years who participated in the European Randomized Study of Screening for Prostate Cancer and who were screened by means of a digital rectal examination, transrectal ultrasonography, and a PSA test, with a threshold value of 4.0 ng per milliliter for biopsy. A priori prevalence assessment (the estimated probability of detecting prostate cancer on the basis of the outcome of the PSA test, prostate volume, digital rectal examination, and transrectal ultrasonography before biopsy) showed that in this sample, in which 93 percent of all indicated biopsies were carried out, 31.9 percent of prostate cancers were missed is evident that below the threshold value of 4.0 ng per milliliter on the PSA test, most cancers were missed by digital rectal examination and transrectal ultrasonography. The proportion of missed cancers was 69.2 percent at a PSA value between 0 and 2.9 ng per milliliter and 46.8 percent at a value between 3.0 and 3.9 ng per milliliter, but cancer-detection rates were exceedingly low when the PSA value was below 2.0 ng per milliliter.

At first glance, the recommendation to lower the age limit for prostate-cancer screening to less than 50 years seems sensible. The deaths from prostate cancer that occur in men 60 to 70 years of age could be prevented by screening at an earlier age, and the number of life-years saved is greater in these younger men. However, the number of tests that would need to be done would be excessive because of the low incidence and the resulting low detection rates.

A mechanism that identifies young men with a high likelihood of having clinically evident prostate cancer later in life would be helpful. A study of 1634 men showed that a positive family history (a father or brother with prostate cancer) doubled the risk of clinically evident prostate cancer. Another study, however, showed that among men who were 40 to 49 years old, the frequency of PSA values above 2.5 ng per milliliter did not differ according to the presence or absence of a family history of prostate cancer; only 3 of the 343 men in the study were found to have prostate cancer (0.9 percent).A third study suggests that a more powerful way of identifying men who should be screened at a younger age may be to perform a PSA test at approximately 40 years of age, regardless of the family history: a PSA value of greater than 0.60 ng per milliliter (found in 177 of 351 men between the ages of 40 and 49) was associated with a relative risk of 3.6 with respect to the development of prostate cancer within 25 years.

Important questions that remain to be answered are whether the detection of missed cancers will reduce mortality and improve the quality of life among treated patients. Predictions based on prognostic indicators have limited value. A large, randomized study of men with locally confined prostate cancer that was detected clinically (not by screening) showed a significantly lower rate of death from prostate cancer in the group of men who underwent radical prostatectomy than in the watchful-waiting group. After eight years of follow-up, however, the death rate from prostate cancer in the watchful-waiting group was only 13.6 percent, and it was necessary to treat 17 men to prevent 1 death from prostate cancer eight years after the diagnosis.

The recommendation to lower the PSA threshold for performing a prostate biopsy to a value below 3.0 or below 2.5 ng per milliliter must be considered on the basis of the characteristics of the PSA test and its overall diagnostic performance. Lowering the PSA threshold for performing a biopsy will increase the rate of overdiagnosis and, potentially, overtreatment. This recommendation is not ready for routine clinical practice. New recommendations for screening should arise from ongoing, randomized studies that are designed to show whether screening indeed reduces mortality from prostate cancer without unacceptably reducing the quality of life.