Screening at the Population Level Trends in Incidence and Mortality

Prostate cancer screening, especially screening with serum PSA in the late 1980s and early 1990s, has profoundly increased the age-adjusted incidence of diagnosed prostate cancer in the United States. Steady rises in the 1970s and early l980s can be attributed to an increase in the number of transurethral resections of the prostate (TURPs) for benign prostatic hyperplasia.2 The subsequent acceleration of incidence can be attributed to increasing use of PSA.3 It should be noted that the use of TURP actually decreased during the late 1980s.

A more recent decline in the incidence of prostate cancer may be due to a clearing of the prevalent cases. It may also be due to the fact that several organizations began recommending against prostate cancer screening in the early 1990s. By 1993, a number of American organizations that publish screening recommendations recommended against screening for prostate cancer or took the position that it was unproven.4 Medicare data indicate that the rate of PSA testing in men aged 65 years and over rose 12-fold from 1988 to 1991, and the proportion of men getting a PSA for the first time peaked in 1991 and 1992. Incidence trends track with first-time PSA utilization rates.30,31

Prostate cancer mortality rates have increased over the past 20 years for both African American and Caucasian men although they have declined slightly during the past few years. From 1991 to 1995, there has been a 6.3% decrease in mortality rates. The Surveillance, Epidemiology, and End Results (SEER) mortality rate has not gone below the baseline mortality rate of the late 1970s and early 1980s. While mortality rates rose from 1973 to 1991, the increase is not as dramatic as those for prostate cancer incidence and provides some evidence of length bias (the diagnosis of tumors with relatively less life-threatening potential than symptomatic cancer). An increased rate of rise in prostate cancer mortality in the late 1980s may be related to the increase in incidence. As diagnostic abilities improved slightly, more deaths are attributed to the disease, a form of attribution bias. Curiously, at the very same time, when prostate cancer incidence in the United States began to fall so precipitously, prostate cancer mortality also began to fall slightly. Some have taken this mortality fall as a priori evidence of a benefit from nationwide screening.32 However, in addition to the fact that changes in treatment practice have occurred in recent years, shifts in mortality may also be due, at least in part, to fewer diagnoses of prostate cancer prior to death. If, in fact, the recent decrease in mortality is due to screening efficacy, it has occurred much more quickly than most would have guessed; and mortality benefits should occur much more quickly in the ongoing randomized screening trials in the United States and Europe than initially estimated.

The data clearly demonstrate that length bias and overdiagnosis may be important confounders in analyzing prostate cancer incidence and mortality trends in the PSA screening era. Prostate cancer screening and treatment patterns vary widely throughout the United States. An assessment of the age-adjusted incidence patterns among Caucasian men in nine American population-based cancer registries from the early 1970s to 1994 showed widely varying incidence of diagnosed cancers as well as use of radical prostatectomy. The regional data also suggest caution in attributing recent declines in mortality to screening. There is no geographic correlation between incidence and mortality rate (Figure 12-2). Indeed, the area with the greatest decrease in mortality, Connecticut, had the lowest rate of screening and lowest incidence during this period from 1973 to 1995.

International comparisons of rates are also useful. Comparisons of age-adjusted prostate cancer rates in Caucasian men in the United States and United Kingdom show a widely varying incidence but similar mortality. Prostate cancer screening is not as widespread in the United Kingdom as it is in the United States. Moreover, a smaller proportion of men diagnosed with localized disease are treated with radical prostatectomy. Despite consistently higher incidence rates in the United States, with a more recent dramatic rise and fall in incidence, compared to the United Kingdom, mortality rates are extremely similar from the 1960s to the 1990s (Figure 12-3). This again suggests that greater detection efforts in the United States find a higher proportion of tumors that are not clinically significant.33

Likewise, the uncertainty about the efficacy of treatment of localized prostate cancer has led to a 20-fold difference in prostatectomy rates per 100,000 among Medicare beneficiaries in the states of Rhode Island versus Alaska.34 Nevertheless, the age-adjusted mortality rates for Caucasian males in the states of Rhode Island and Alaska are very similar.35

Potential Adverse Consequences of Treatment


Much of the enthusiasm for screening stems from the desire to avoid the suffering from advanced prostate cancer that screening and treatment could, in theory, prevent. Screening and subsequent treatment, however, cause considerable morbidity. All those who receive treatment are at risk for the morbidities of therapy, including those who are cured unnecessarily and those who need to be cured but are not. The men in these two categories experience all the morbidities of local therapy but none of the benefits. In fact, they experience them sooner and for a longer time since screening advances their date of diagnosis without extending lifespan. A recent study of Medicare beneficiaries36 notes that of 3173 undergoing radical prostatectomy from l985 to 1991, less than 60% were found to have organ-confined disease. Five years after surgery, the proportion of men receiving additional therapy for cancer recurrence or persistence was about 35%. Even in men with pathologically confined cancer after radical prostatectomy, the cumulative incidence of additional prostate cancer treatment at 5 years was 25%.

The morbidities of prostate cancer treatment are better defined than the efficacy of the treatment itself. All forms of localized prostate cancer therapy have side effects but those for radical prostatectomy and external beam radiation are best described. Both are known to cause impotence, rectal injury, urinary incontinence, and urethral stricture. Literature reviews from physicians at major medical centers give impotence rates of 25 to 40%, rectal injury rates of 1 to 3%, urinary incontinence rates of 3 to 6%, and urethral stricture rates of 8 to 18%, with radiation therapy at the lower range compared to surgery.37

Morbidity is a highly subjective factor, and patient-reported morbidities from surveys are substantially higher than physician-reported morbidity rates. In a survey of Medicare patients38 undergoing radical prostatectomy from 1988 to 1992, 30% reported the chronic need for pads and urinary clamps. More than 60% reported a problem with wetting, 60% reported having no erections since surgery, and 90% reported no erections sufficient for intercourse in the month prior to answering the survey. Twenty-eight percent reported receiving follow-up treatment for recurrence of prostate cancer within 4 years of prostatectomy. It is not clear if the newer "nerve-sparing" or anatomic prostatectomy has solved the problem of postsurgical sexual impotence. In a study of patients treated with the newer procedure, the self-reported frequency of impotence and urinary incontinence was similar to that found in the survey of Medicare patients, even though the average age of those in the nerve-sparing study was younger than that in the Medicare survey.39 Although statistical power was limited, sexual dysfunction and urinary dysfunction did not seem to differ substantially between men who had undergone standard versus nerve-sparing radical prostatectomy. Radiation therapy also confers significant risk of morbidity.40 Clearly, more information is needed in this area.

Prostatectomy incurs a higher risk of treatment-related death than radiation therapy.38 While individual surgeons have reported death rates of less than 0.5% depending on patient selection and the surgeon's skill, the surgical mortality rate was 2% in a national sample of Medicare beneficiaries. Unfortunately this study included only men aged 65 years and over, but this age group does include more than 80% of all men with prostate cancer. In that same series, 8% of men suffered major cardiopul-monary complications after radical prostatectomy.

Economic Costs

It has been estimated that PSA screening for all men aged 50 to 74 years without pre-existing cardiac disease would add $12 to $26 billion in the first year of a nationwide screening campaign.41-43 Such a cost would divert the finite health care budget from interventions of proven and known effectiveness. If prostate cancer screening is not of substantial benefit, this would result in a net loss in the overall health of the nation. If screening is proven effective, therefore, it would be important to compare its

FIGURE 12-2. Prostate cancer incidence and mortality comparisons showing no correlations.

cost-effectiveness to that of other beneficial medical interventions in men.


The medical community is in a very unfortunate position because it has taken so long to put its assumptions about prostate cancer screening and treatment to definitive testing. Lead-time bias and length bias cloud interpretation of previous prostate cancer screening data. Radical prostatectomy series demonstrate that a substantial number of men treated for localized disease ultimately relapse; autopsy, observation, and epidemiologic studies suggest that many men diagnosed with prostate cancer do not have clinically significant disease given their risk for competing causes of death. Indeed, if there is some benefit, it may be counterbalanced by harm to many more.

The only way to demonstrate that screening saves lives and gauge the net benefits and harms is through a well-designed randomized trial with an "intention-to-screen" analysis of men as randomized. A randomized trial of prostate cancer screening began in the United States in 1993.37 Several other trials are underway in Europe.44 In addition, trials of definitive surgery and radiation have also begun.19 If such trials had been launched just 5 years earlier, we would likely have results by now.

The current state of knowledge does not permit a fully informed decision with regard to routine prostate cancer screening and subsequent management. Ongoing trials should inform the disagreements over screening effectiveness. Organizations taking a skeptical view of prostate cancer screening include the United States Preventive Ser-

FIGURE 12-3. Prostate cancer incidence and mortality trends in the United States and the United Kingdom (1968-1995).

vices Task Force, the American College of Physicians, and the Canadian Task Force on the Periodic Health Examination.45-49 While most organizations issuing screening recommendations have not advocated prostate cancer screening, recently the major American organizations that had previously suggested that men be screened evaluated the more recent data and moved away from a recommendation that "screening should be done" and toward informed education as to the benefits and risks of screening and patient choice. The National Cancer Institute does not have a position for or against prostate screening and is currently conducting a large prospective randomized trial testing the value of DRE and PSA testing in the screening setting. In the meantime, while results of this and other randomized trials are pending, health professionals should inform each man about the current state of knowledge, detail the known risks and theoretic benefits, encourage participation in clinical trials whenever possible, and reassure the individuals that for now there is no clear-cut right or wrong choice regarding their decision to be screened or not.


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  • Mikael
    What are the incident rate in prostate screening?
    2 months ago

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