": Prostate cancer is the most common malignancy diagnosed in men. Screening by prostate-specific antigen (PSA) testing is widespread in the United States, and treatment recommendations often urge early therapy. Yet there is ongoing controversy about patient care because of a lack of evidence demonstrating that such an aggressive approach improves the length and quality of a man's life. Drs Wilt and Partin review the epidemiologic factors of prostate cancer and discuss the research findings, recommendations, and pros and cons of screening and therapy. Further, they make a case that rather than routinely ordering a PSA test for all men, physicians should inform patients about the potential but uncertain benefits and the possible harm of screening and treatment and then incorporate patient preferences into decision making. "

"Wilt TJ, Partin MR. Prostate cancer intervention: involving the patient in early detection and treatment. Postgrad Med 2003;114(4):43-9"

"nnually in the United States, about 190,000 new cases of prostate cancer are diagnosed and 30,000 men die of the disease (1). Early detection and treatment of prostate cancer could theoretically reduce the burden of this potentially disabling and deadly disease. However, because no conclusive, direct evidence demonstrates that early detection and treatment improve length or quality of life, the value of prostate cancer screening remains controversial. "

" Prostate cancer is primarily a disease of elderly men. About 85% of all cases of prostate cancer are diagnosed in men older than 65 years, and 90% of deaths due to this disease are in men over age 65 (2). Prostate cancer is diagnosed in very few men younger than 50 years (<0.1% of all patients with prostate cancer). "

" With the advent of PSA screening, the lifetime risk of being diagnosed with prostate cancer is about 17% (1 in 6), making it the most common malignancy in men. However, the lifetime risk of death from prostate cancer is about 3% (1 in 29). The relatively high ratio of prostate cancer incidence to mortality was evident even before the widespread use of PSA testing and aggressive treatment. This high ratio is likely due to the slow doubling time of early prostate cancer and the fact that prostate cancer is often diagnosed in elderly men who have comorbid conditions and are therefore more likely to die of other causes. "

" Although the cause of prostate cancer is not known, risk of this disease is associated with age, ethnicity, and a family history of prostate cancer ("

"). African American men have an incidence rate about 60% greater and a mortality rate twofold higher than white men. Men who have a first-degree relative with prostate cancer have a twofold increase in risk of the disease. Some studies have demonstrated an association between prostate cancer and a high dietary intake of fat, red meat, and dairy products (calcium) (2). Inverse associations have been observed in men who have a diet high in soy, tomato-based products (lycopenes), selenium, or vitamin E. The presence of increased prostate size (benign prostatic hyperplasia [BPH]) or the lower urinary tract symptoms associated with BPH, or both, does not increase prostate cancer risk (3). "

" The age-adjusted prostate cancer mortality rate has declined in the United States by about 19% during the past decade. Additionally, the 5-year prostate cancer-specific survival rate has improved by almost 50% since 1950 (4). Although these percentages are encouraging, it is difficult to attribute the improvements solely to early detection and treatment. In the United States and Canada, geographic areas and health plans that have the highest rates of detection and early treatment do not have the lowest rates of prostate cancer death (5). Furthermore, although the number of men diagnosed with prostate cancer has increased in the United States by about 80 per 100,000 since the early 1990s, prostate cancer mortality has only decreased by 4 per 100,000 and remains greater than it was in the 1970s (6). "

" The declines in prostate cancer mortality may be explained by improved therapy for advanced disease or misattribution of cause of death, or both. The observed improvements in 5-year prostate cancer survival have little relationship with changes in cancer mortality and should not be used as a measure of treatment effectiveness (4). They more accurately reflect the changing patterns of cancer diagnosis and the lead and length bias associated with cancers detected by screening. This situation results in men with screening-detected disease living longer with the knowledge that they have prostate cancer regardless of whether testing and treatment are beneficial. "

" Two basic strategies have been proposed for prostate cancer screening: the digital rectal examination and the PSA blood test. In men undergoing first-time testing, cancer detection rates are about 3% with digital rectal examination alone, 5% with PSA testing alone, and 6% with the two tests combined (1). Detection rates decrease substantially with subsequent testing. "

" Digital rectal examination has a lower ability to detect cancer than PSA testing and has poor reproducibility even among experienced examiners. Its efficacy in reducing prostate cancer mortality has not been confirmed. Three out of four case-controlled studies concluded that digital rectal examination was not associated with a statistically significant reduction in the odds of advanced prostate cancer or in prostate cancer mortality (1,7). The only randomized trial to report on the efficacy of PSA screening (8) was flawed by a low adherence rate in the group invited to receive screening. Using an intention-to-screen analysis, there was no difference in prostate cancer deaths among the invited group (4.6%) and the group that was not invited (4.8%). "

" The US Preventive Services Task Force (USPSTF) report "Screening for Prostate Cancer: Recommendations and Rationale" (1) stated in its summary that there was "good evidence that PSA screening can detect early-stage prostate cancer but mixed and inconclusive evidence that early detection improves health outcomes. Screening is associated with important harms, including frequent false-positive results and unnecessary anxiety, biopsies, and potential complications of treatment of some cancers that may never have affected a patient's health. The USPSTF concludes that evidence is insufficient to determine whether the benefits outweigh the harms for a screened population." "

" Despite this lack of conclusive evidence, PSA testing is more common than colorectal cancer screening, a practice demonstrated to reduce colorectal cancer mortality (9). An estimated 75% of men 50 years of age or older have had at least one PSA test. Even among men very unlikely to benefit because of their advanced age, PSA testing is common. In men aged 80 years or older, 56% reported receiving prostate cancer screening with a PSA test in the past year, compared with 25% receiving colorectal cancer screening. "

" Problems with sensitivity and specificity using typical PSA testing strategies (annual PSA testing and referral if PSA >4.0 ng/mL) result in missing clinically significant prostate cancers or performing unnecessary biopsies, or both (1). The sensitivity of a PSA test with a cutoff point of 4.0 ng/mL for detecting prostate cancer ranges from 63% to 83% (1). Among men who were not diagnosed with prostate cancer over 10 years, 9% had an initial PSA level of 4.0 ng/mL or greater (specificity, 91%). PSA testing specificity is reduced in men with an enlarged prostate gland or lower urinary tract symptoms, because these conditions raise PSA levels but do not increase the risk of prostate cancer (1,3). "

" The following clinical scenario is illustrative. Among 1,000 asymptomatic men aged 60 to 69 years with no previous prostate cancer screening, about 150 would have a PSA level of 4.0 ng/mL or greater (for men in their 70s, about 270 would have a PSA level of 4.0 ng/mL or greater). These men often require further evaluation by prostate biopsy. Of the 150 men, about 40 would have prostate cancer and 110 would have no prostate cancer. About 80% to 90% of the men with prostate cancer detected by PSA testing would have clinically localized disease. "

" Because the lead time associated with PSA testing (compared with clinical detection) is about 10 years, the vast majority of prostate cancers detected by PSA testing will not result in symptomatic progression for at least 15 years (1). Whether early intervention extends or improves the life of men with PSA-detected prostate cancer is not known. However, it is estimated that as many as 50% of prostate cancers detected by PSA testing will never cause symptoms and by definition are overdiagnosed (10). "

" To overcome the problems of PSA sensitivity and specificity, a variety of diagnostic parameters and tests have been proposed. However, none have proved to be beneficial or superior to the current PSA reference ranges. Decreasing the PSA cutoff point for further evaluation from 4.0 to 3.0 ng/mL would increase the percentage of men undergoing biopsies by an absolute 6% to 11% (11). Studies evaluating the ability to use PSA levels as a function of time (PSA velocity and PSA change) are inconclusive. Because of intraindividual variation, the PSA velocity is most useful if three or more measurements are obtained over an interval of 1 to 3 years (11). In these situations, an abnormal PSA velocity has been defined as a PSA increase of 0.75 ng/mL or more per year. "

"-antichymotrypsin. Men with prostate cancer tend to have a lower percentage of PSA in the free form compared with men without prostate cancer. Measurement of the free-total PSA ratio, or the percent free PSA (%fPSA), may help differentiate between prostate cancer and benign prostate conditions among men with PSA concentrations between 4 and 10 ng/mL. A policy to not perform biopsies on men with a total PSA level between 4.0 and 9.9 ng/mL and a %fPSA greater than 25% would avoid about 20% of biopsies currently performed. However, these men would still have an 8% probability of prostate cancer (12). Whether this level is low enough for patients and physicians to withhold biopsy is not clear. "

" For men undergoing PSA testing, preliminary evidence from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial indicates that almost 99% of men with a baseline PSA level of less than 1 ng/mL would remain negative (ie, PSA <4.0 ng/mL) after 4 subsequent years of annual PSA testing. Additionally, 99% of men with a PSA level of 1 to 2 ng/mL would have negative PSA tests the following year. A strategy of PSA screening every 5 years for men with a PSA level below 1 ng/mL and every 2 years for men with a PSA level in the range of 1 to 2 ng/mL would produce a 55% reduction in the number of PSA tests, and it would result in only a small percentage of men missing an earlier "positive" test. The estimated cost savings of this strategy is $1 billion per year. "

" In the absence of definitive evidence about the relative benefits of detection and treatment strategies, patients seek information and recommendations from many sources. Rather than making a recommendation for or against routine PSA testing, physicians should provide information about the potential benefits and established harms of screening and treatment (1). Patient preference should then be incorporated into the decision about whether to request PSA testing. This approach of shared decision making should focus on men who inquire about prostate cancer testing, are 50 years of age or older, and have a life expectancy of at least 10 to 15 years (1,13). "

" At a minimum, the information should include details about the potential magnitude and seriousness of prostate cancer, the likelihood that prostate cancer will be diagnosed, the possibilities of false-positive and false-negative results from screening, anxiety intervention and additional interventions associated with a positive test result, and the uncertainty about whether screening reduces the risk of dying of prostate cancer (1) (see box at end of article). Physicians should advise against prostate cancer testing in men who are more likely to be harmed than helped by screening (eg, due to advanced age, comorbid conditions, or the desire to not receive early intervention). "

" Providing this information in a manner that is balanced, accurate, and comprehensible and helping patients identify and incorporate their values and preferences into decision making can be difficult, complex, and time-consuming (14). "

" Patients may question why it is important to deliberate over a simple, low-cost blood test that seemingly
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