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PSA screening controversy increases with release of mortality studies with conflicting results, modest benefits

Wednesday, April 08 2009 | Comments

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What's This? The controversy surrounding prostate-specific antigen (PSA) screening is only going to increase following the release of data from 2 studies that showed either no mortality benefit from PSA screening or a small benefit that was overshadowed by overdiagnosis and overtreatment concerns.

In the first study, the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial, no difference was seen in mortality rates between patients who underwent PSA screening and those who did not, while in the second trial, the European Randomized Study of Screening for Prostate Cancer (ERSPC), PSA-based screening reduced the mortality rate from prostate cancer by 20% but resulted in a large number of men who would need to be screened and then treated to prevent a single prostate cancer death.

The PLCO trial included 76,693 men who were randomized to receive annual screening (n=38,343)--annual PSA testing for 6 years and digital rectal examinations for 4 years--or usual care (n=38,350). Sometimes screening was done in the usual care group, as recommended by some organizations.

An intention-to-screen comparison of prostate-specific mortality between the 2 study groups was the primary outcome, calculated as event rates (defined as the ratio of the number of events in a given time period to the person-years at risk for that event).

After 7 years of follow-up, there were 2,820 cancers in the screening group and 2,322 cancers in the control group, which translated to an incidence of prostate cancer per 10,000 person-years of 116 in the screening group and 95 in the control group (rate ratio [RR], 1.22; 95% CI, 1.16-1.29). After 10 years of follow-up, there were 3,452 cancers in the screening group and 2,974 cancers in the control group (RR, 1.17; 95% CI, 1.11-1.22).

There were 50 deaths in the screening group and 44 deaths in the control group after 7 years, which translated to an incidence of death per 10,000 person-years of 2.0 in the screening group and 1.7 in the control group (RR, 1.13; 95% CI, 0.75-1.70). After 10 years, there were 92 deaths in the screening group and 82 deaths in the control group (RR, 1.11; 95% CI, 0.83-1.50).

"Risks incurred by screening, diagnosis, and resulting treatment of prostate cancer are both substantial and well-documented in the literature," the authors concluded. "To the extent that overdiagnosis occurs with prostate cancer screening, many of these risks occur in men in whom prostate cancer would not have been detected in their lifetime had it not been for screening." (Andriole GL, et al. N Eng J Med 2009;360:1310-1319.)

The ERSPC trial included 162,243 men aged 55 to 69 years who were randomized into a group that was offered PSA screening at an average of once every 4 years or to a control group that was not offered such screening. Prostate cancer mortality rate was the primary endpoint of the trial.

Of the men in the screening group, 82.2% accepted >=1 offer of screening.

Results from a median follow-up of 9 years showed that the cumulative incidence of prostate cancer was 8.2% (n=5,990) in the screening group and 4.8% (n=4,307) in the control group.

A total of 214 deaths were recorded in the screening group, versus 326 deaths in the control group. The unadjusted risk of death was 20% lower in the screening group as compared with the control group (RR, 0.80; 95% CI, 0.67-0.95; P=.01) and remained similar after adjusting for other factors (RR, 0.80; 95% CI, 0.65-0.98; P=.04).

The absolute difference between the groups was 0.71 prostate cancer death per 1,000 men, meaning that 1,410 men would need to be screened during a 9-year period to prevent 1 prostate cancer death. In addition, 48 men would have to be treated in this period to prevent 1 death.

"The high number of men who would need to be treated could be improved by avoiding the diagnosis and treatment of indolent cancers during screening or by improving treatment in the remaining men with cancer," the authors commented.

"Although the results of our trial indicate a reduction in prostate cancer mortality associated with PSA screening, the introduction of population-based screening must take into account population coverage, overdiagnosis, overtreatment, quality of life, cost, and cost effectiveness," they concluded. (Schroder FH, et al. N Eng J Med 2009;360:1320-1328.)

In an editorial roundtable published in the same issue of the journal, Drs. Mary McNaughton-Collins and Philip Kantoff debated the significance of the findings.

Both physicians acknowledged that there was a lot of uncertainty about the benefits of PSA screening versus the risks of overdiagnosis and overtreatment.

Dr. McNaughton-Collins said she thought the PSA screening controversy would die down once the medical community has the ability to distinguish indolent cancers that do not need to be treated from aggressive ones that do need to be treated.

Dr. Kantoff said he would like to see the whole process of PSA screening disassociated from treatment, "because I do believe that many people who get diagnosed with prostate cancer do not need to be treated." (Lee TH, et al. N Eng J Med 2009;360:e18.)

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