To Screen or not to Screen: the Prostate Cancer Screening Controversy

February 26, 2010

INTRODUCTION
Prostate cancer is the most common non-skin cancer, and second only to lung cancer as a leading cause of cancer death in men in the United States. "In 2008, an estimated 186,320 prostate cancer cases will be diagnosed, and about 28,660 deaths are expected." (1)

For a man in the U.S., the lifetime risk of developing prostate cancer is 1 in 6. Yet, the risk of dying from prostate cancer is 2.9 percent. (1) Many cases of prostate cancer do not become clinically evident. Autopsy studies have revealed that one-third of men under the age of 80 and two-thirds of older men had evidence of prostate cancer. (1)

SCREENING TOOLS

There are multiple screening mechanisms available to detect prostate cancer.

Prostate specific antigen (PSA) — is a glycoprotein produced by prostate epithelial cells. PSA levels may be increased in men with prostate cancer because PSA production is increased and "tissue barriers between the prostate gland lumen and the capillary are disrupted allowing for the release of more PSA into the serum." (1) It should be noted that benign conditions such as benign prostatic hyperplasia (BPH) and prostatitis also serve to increase serum PSA levels. The commonly accepted standard total PSA cutoff is 4.0 mg/mL "because it balances the tradeoff between missing important cancers at a curable stage and avoiding detection of clinically insignificant disease and subjecting men to unnecessary prostate biopsies." (1)

Digital rectal exam (DRE) — is a longstanding screening mechanism for prostate cancer. DRE allows for tumor detection in the posterior and lateral aspects of the prostate gland. Abnormal exam findings include nodules, asymmetry, or induration. Stage T1 tumors, by definition, are not palpable. "An inherent limitation of DRE is that only 85 percent of cancers arise peripherally where they can be detected" via digital examination. (1)

Combined PSA/DRE — Multiple investigators have reported that combining PSA and DRE can increase the overall rate of cancer detection.

Other testing mechanisms are available but, for various reasons, are not recommended for screening purposes. Transrectal ultrasonography (TRUS) is an outpatient procedure that is tolerated well by most men and requires no sedation or analgesia. It has a low sensitivity and positive predictive value. TRUS is not available in many primary care clinics. Therefore, its use is generally for guidance of prostate biopsy rather than detection. Transrectal prostate biopsy is another outpatient technique, but its use for screening purposes is limited primarily by cost, the unacceptability to large numbers of patients, and the need for urological referral. Biopsy complications include mild rectal spotting, hematospermia, or hematuria. On occasion, patients experience greater rectal bleeding or sepsis. (1)

THE SCREENING CONTROVERSY

Because many cases of prostate cancer do not become clinically evident, medical experts disagree about whether prostate cancer screening is right for all men. It is not clear if the benefits of screening outweigh the risks.

In March 2009, the New England Journal of Medicine published initial reports from two large, randomized trials that studied the mortality results from prostate cancer screening. The results of these studies — the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening trial on prostate-cancer mortality and the European Randomized Study of Screening for Prostate Cancer (ERSPC) — failed to provide definitive answers or clear-cut recommendations. Rather, these study reports have continued the discussion of the screening controversy. The PLCO study found that "after 7 to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly" between the study group of men who were screened and the control group of men who received usual care. (2) The ERSPC study concluded that "PSA-based screening reduced the rate of death from prostate cancer by 20% but was associated with a high risk of overdiagnosis." (3)

Screening is not without risk of complications. While prostate biopsies rarely (less than 1 percent) cause complications serious enough to require hospitalization, they can cause discomfort and anxiety. In one study, 55 percent of patients reported discomfort, with 2 percent reporting persistent pain for longer than one week. While a cancer diagnosis causes psychological distress, a negative prostate biopsy may also produce chronic anxiety due to the lack of certainty of the results given the relatively high false-negative biopsy rate. (1)

Jennifer Stark, an epidemiologist at the Harvard School of Public Health and lead author of an essay in the British Medical Journal, noted that PSA is an imperfect screening tool. "PSA screening cannot differentiate between indolent and lethal prostate cancer." She said that the PSA test tends to direct patients toward "diagnostic biopsies and treatment with no certainty of mortality benefit but with much anxiety and overtreatment." (4) Medscape Oncology reports that in the United States, the PSA test has initiated the overtreatment of an estimated 1 million men since the onset of widespread PSA screening in the mid-1980s. (4)

SCREENING RECOMMENDATIONS AND GUIDELINES

Medical associations and societies have published conflicting recommendations regarding prostate cancer screening; however, none of these organizations reissued their guidelines after the publication of the ERSPC and PLCO studies. The United States Preventive Services Task Force and many European cancer societies have not endorsed routine PSA screening to detect prostate cancer.

The American Cancer Society and American Urological Association recommend that men consider prostate cancer screening after discussing the risks and benefits with a health care professional. (5) "The ACS recommends that serum PSA testing and DRE should be offered annually to men 50 years of age and older who have a life expectancy of 10 years. The guidelines also stress the benefit of screening beginning at age 45 in patients at high-risk of developing prostate cancer (e.g., black men and men with a first-degree relative with prostate cancer diagnosed at a younger age). PSA testing is recommended for men who ask their physicians to make the decision about screening on their behalf. The American Urological Association (AUA) also supports this policy (6)

The American College of Physicians recommends that "Rather than screening all men for prostate cancer as a matter of routine, physicians should describe the potential benefits and known harms of screening, diagnosis, and treatment; listen to the patient's concerns; and then individualize the decision to screen." According to the ACP, men between the ages of 50 to 69 years are most likely to benefit from screening. (6)

More information on prostate cancer screening guidelines is available at the following web sites:

TO SCREEN OR NOT TO SCREEN

"Although screening for prostate cancer with PSA can reduce mortality from prostate cancer, the absolute risk reduction is very small. Given limitations in the design and reporting of the randomized trials, there remain important concerns about whether the benefits of screening outweigh the potential harms to quality of life, including the substantial risks for overdiagnosis and treatment complications. Given the tradeoffs between potential benefits and harms involved with screening for prostate cancer, and the lack of definitive data on screening outcomes, it is particularly important that patients make informed decisions about undergoing testing." (6)

In light of the current screening controversy, a shared decision-making approach to PSA screening by the physician and patient becomes critical. (For more on shared decision-making, please see the article "Shared decision-making: moving beyond informed consent" in the March-April 2010 issue of the Reporter.) "We recommend an open, blunt discussion between clinician and patient about the relevance, risks and benefits of screening prior to any screening test so as to not to allow the screening results to bias the patient's treatment decisions." (7)

SOURCES

  1. Hoffman R. Screening for prostate cancer. UptoDate. May 1, 2009.
  2. Andriole GL, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:1310-1319.
  3. Schroder FH, et al. Screening and prostate-cancer mortality in a randomized European study. N. Engl J Med. 2009;360:1320-1328.
  4. Mulcahy N. PSA test is imperfect tool: what to do? Medscape Medical News. October 1, 2009. Available at http://www.medscape.com/viewarticle/709798. Accessed March 18, 2010.
  5. Hoffman RM. Patient information: prostate cancer screening. UpToDate. June 11, 2009.
  6. Hoffman RM. Screening for prostate cancer. UptoDate. September 1, 2009.
  7. Barry M. Screening for prostate cancer — the controversy that refuses to die. N Engl J Med. 2009;360:1351-1354.
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