PSA SCREENING

Today I want to talk about selective screening for prostate cancer based on a study by Preston and colleagues.^[1] They looked at men who were participants in the Physicians' Health Study and for whom there were 30 years of follow-up. Blood samples from the time of study initiation were obtained and then analyzed for baseline prostate-specific antigen (PSA) levels.

Men were divided into three age groups: 40-49 years, 50-54 years, and 55-59 years. They compared men who developed lethal prostate cancer with those who were not diagnosed with prostate cancer over the 30-year period.

They found that baseline PSA was very predictive of risk of developing lethal cancer in the future. For example, if men had a greater than 90th percentile PSA at baseline, the odds ratio of developing lethal cancer ranged from 6.9 [55-59 years] to 12.6 [50-54 years] over the 30-year follow-up period.

The study is extremely well done and raises some interesting and provocative questions. But first, I have some concerns. There were wide confidence intervals around each of the data points; thus, the robustness of their findings may be far less than presented. The study authors suggested that if a man has a baseline PSA at the age of 45 years that falls below the median for his age group, then he need not undergo another PSA for at least 5 years, and then only periodically thereafter. Men aged 60 years or older who fall below the median for their age group can stop screening entirely.

If we tell men over age 60 years that they no longer need to be tested because their median PSA is so low, does that guarantee that they will never develop lethal cancer? The answer is: no. The odds are low, but they are not zero. The same is true for men who are 45 years old. Their odds of developing lethal cancer are also low, but they are not zero. There could be medicolegal implications of telling men to either not be screened anymore or to be screened less often, because some will ultimately be diagnosed with a lethal cancer.

Another question is, what are the implications for men whose PSA levels are above the 90th percentile? How often should they be followed? At what PSA level should a biopsy be done? Should men undergo treatment, for example, if their Gleason scores are 6? These questions are not easily answered at this time and may not be determined without a proper prospective randomized trial. As we know from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), there are many problems associated with doing such a study, and of course, men may not follow the rules or suggestions anyway.

Can we use these data for a different set of recommendations to make the risk/benefit of screenings more favorable? The answer is: possibly yes. Unless a randomized study is done, there will be considerable uncertainty about whether we can save men's lives by doing a biopsy with a PSA of 1.5 ng/mL, 2 ng/mL, or 3 ng/mL, and about how often we need to screen in the first place.

For now, we have some very provocative data in a well-done study but are left with many unanswered questions. Even with these good data, it's difficult to justify making recommendations for selective screening.

I look forward to your comments. Thank you.