Prostate cancer screening

Overview
Prostate cancer screening is an attempt to find unsuspected cancers. Screening tests may lead to more specific follow-up tests such as a biopsy, where small cores of the prostate are removed for closer study. Prostate cancer screening options include the digital rectal exam and the prostate specific antigen (PSA) blood test. Screening for prostate cancer is controversial because it is not clear if the benefits of screening outweigh the risks of follow-up diagnostic tests and cancer treatments.

Prostate cancer is usually a slow-growing cancer, very common among older men. In fact, most prostate cancers never grow to the point where they cause symptoms, and most men with prostate cancer die of other causes before prostate cancer has an impact on their lives. The PSA screening test may detect these small cancers that would never become life threatening. Doing the PSA test in these men may lead to overdiagnosis, including additional testing and treatment. Follow-up tests, such as prostate biopsy, may cause pain, bleeding and infection. Prostate cancer treatments may cause urinary incontinence and erectile dysfunction. Therefore, it is essential that the risks and benefits of diagnostic procedures and treatment be carefully considered before PSA screening.

Several medical societies have not found sufficient evidence to support routine screening for prostate cancer - but the American Urological Association supports annual screening and digital examination for men over 50 years old - and starting earlier for 'men at high risk (those with a family history of prostate cancer or African American men)'.
 * In 2002, the U.S. Preventive Services Task Force (USPSTF) concluded that the evidence was insufficient to recommend for or against routine screening for prostate cancer using PSA testing or digital rectal examination (DRE). The previous 1995 USPSTF recommendation was against routine screening.
 * In 1997, American Cancer Society (ACS) guidelines began recommending that beginning at age 50 (age 45 for African-American men and men with a family history of prostate cancer, and since 2001, age 40 for men with a very strong family history of prostate cancer), PSA testing and DRE be offered annually to men who have a life-expectancy of 10 or more years (average life expectancy is 10 years or more for U.S. men under age 76) along with information on the risks and benefits of screening. The previous ACS recommendations since 1980 had been for routine screening for prostate cancer with DRE annually beginning at age 40, and since 1992 had been for routine screening with DRE and PSA testing annually beginning at age 50.
 * The 2007 National Comprehensive Cancer Network (NCCN) guideline recommends offering a baseline PSA test and DRE at ages 40 and 45 and annual PSA testing and DRE beginning at age 50 (with annual PSA testing and DRE beginning at age 40 for African-American men, men with a family history of prostate cancer, and men with a PSA ≥ 0.6 ng/mL at age 40 or PSA > 0.6 ng/mL at age 45) through age 80, along with information on the risks and benefits of screening. Biopsy is recommended if DRE is positive or PSA ≥ 4 ng/mL, and biopsy considered if PSA > 2.5 ng/mL or PSA velocity ≥ 0.35 ng/mL/year when PSA ≤ 2.5 ng/mL.
 * Some U.S. radiation oncologists and medical oncologists who specialize in treating prostate cancer recommend obtaining a baseline PSA in all men at age 35 or beginning annual PSA testing in high risk men at age 35.
 * The American Urological Association Patient Guide to Prostate Cancer.

Since there is no general agreement that the benefits of PSA screening outweigh the harms, the consensus is that clinicians use a process of shared decision-making that includes discussing with patients the risks of prostate cancer, the potential benefits and harms of screening, and involving the patients in the decision.

However, because PSA screening is widespread in the United States, following the recommendations of major scientific and medical organizations to use shared decision-making is legally perilous in some U.S. states. In 2003, a Virginia jury found a family practice residency program guilty of malpractice and liable for $1 million for following national guidelines and using shared decision-making, thereby allowing a patient (subsequently found to have a high PSA and incurable advanced prostate cancer) to decline a screening PSA test, instead of routinely ordering without discussion PSA tests in all men ≥ 50 years of age as four local physicians testified was their practice, and was accepted by the jury as the local standard of care. An estimated 20 million PSA tests are done per year in North America and possibly 20 million more outside of North America.
 * In 2000, 34.1% of all U.S. men age ≥ 50 had a screening PSA test within the past year and 56.8% reported ever having a PSA test.
 * In 2000, 33.6% of all U.S. men age 50–64 and 51.3% of men age ≥ 65 had a PSA test within the past year.
 * In 2005, 33.5% of all U.S. men age 50–64 had a PSA test in the past year.
 * 37.5% of men with private health insurance, 20.8% of men with Medicaid insurance, 14.0% of currently uninsured men, and 11.5% of men uninsured for > 12 months.
 * In 2000–2001, 34.1% of all Canadian men age ≥ 50 had a screening PSA test within the past year and 47.5% reported ever having a screening PSA test.
 * Canadian men in Ontario were most likely to have had a PSA test within the past year and men in Alberta were least likely to have had a PSA test with the past year or ever.

Digital rectal examination
Digital rectal examination (DRE) is a procedure where the examiner inserts a gloved, lubricated finger into the rectum to check the size, shape, and texture of the prostate. Areas which are irregular, hard or lumpy need further evaluation, since they may contain cancer. Although the DRE only evaluates the back of the prostate, 85% of prostate cancers arise in this part of the prostate. Prostate cancer which can be felt on DRE is generally more advanced. The use of DRE has never been shown to prevent prostate cancer deaths when used as the only screening test.

Prostate specific antigen
The PSA test measures the blood level of prostate-specific antigen, an enzyme produced by the prostate. Specifically, PSA is a serine protease similar to kallikrein. Its normal function is to liquify gelatinous semen after ejaculation, allowing spermatozoa to more easily navigate through the uterine cervix.

The risk of prostate cancer increases with increasing PSA levels. 4 ng/mL was chosen arbitrarily as a decision level for biopsies in the clinical trial upon which the FDA in 1994 based adding prostate cancer detection in men age 50 and over as an approved indication for the first commercially available PSA test. 4 ng/mL was used as the biopsy decision level in the PLCO trial, 3 ng/mL was used in the ERSPC and ProtecT trials, and 2.5 ng/mL is used in the 2007 NCCN guideline.

PSA levels can change for many reasons other than cancer. Two common causes of high PSA levels are enlargement of the prostate (benign prostatic hypertrophy (BPH)) and infection in the prostate (prostatitis). It can also be raised for 24 hours after ejaculation and several days after catheterization. PSA levels are lowered in men who use medications used to treat BPH or baldness. These medications, finasteride (marketed as Proscar or Propecia) and dutasteride (marketed as Avodart), may decrease the PSA levels by 50% or more.

Several other ways of evaluating the PSA have been developed to avoid the shortcomings of simple PSA screening. The use of age-specific reference ranges improves the sensitivity and specificity of the test. The rate of rise of the PSA over time, called the PSA velocity, has been used to evaluate men with PSA levels between 4 and 10 ng/ml, but it has not proven to be an effective screening test. Comparing the PSA level with the size of the prostate, as measured by ultrasound or magnetic resonance imaging, has also been studied. This comparison, called PSA density, is both costly and has not proven to be an effective screening test. PSA in the blood may either be free or bound to other proteins. Measuring the amount of PSA which is free or bound may provide additional screening information, but questions regarding the usefulness of these measurements limit their widespread use.

Interpreting the results of screening tests
Two clinical prediction rules help predict the probability of cancer based on the the level of the prostate-specific antigen and other clinical findings.

Randomized controlled trials
One randomized controlled trial found significant reduction in death from screening. However, the intention to treat analysis showed no benefit.

A secondary analysis of a randomized controlled trial suggests screening for prostate cancer every 4 years is adequate. The screening comprises a PSA blood test, a digital rectal exam, and a transrectal ultrasound. "Very few, if any, aggressive prostate cancers escape (this) screening."

Decision analyses
In the absence of well done randomized controlled trials, a decision analysis can estimate the benefit of screening. One analysis found that approximately 303 men would number need to be screened with a "strategy of PSA testing at ages 40 and 45 years followed by biennial testing beginning at age 50" to prevent one death from prostate cancer.

Clinical practice guidelines
Clinical practice guidelines for prostate cancer screening are controversial because the benefits of screening may not outweigh the risks of follow-up diagnostic tests and cancer treatments:
 * U.S. Preventive Services Task Force (USPSTF):
 * "the evidence is insufficient to recommend for or against routine screening for prostate cancer using prostate-specific antigen (PSA) testing or digital rectal examination (DRE). This is a grade I recommendation"


 * American Cancer Society, in 2001, recommended:
 * "The PSA test and the 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 should begin testing at age 45. Information should be provided to patients about benefits and limitations of testing."

The ACS recommends that individual men discuss the potential benefits and risks of testing with their doctors in order to make an informed decision on whether or not to be tested. Screening should be offered annually to African-American men and those with a family history of prostate cancer upon reaching 45 years. Other racial and ethnic groups, such as Asian- and Hispanic-Americans have a lower risk of prostate cancer, and may not benefit from screening. Screening is likely not useful for men over age 70 or with other significant medical problems and a life expectancy of fewer than 10 years.