According to a newly published, prospective study in the Journal of Urology, a research team at the Mayo Clinic has confirmed prior reports (based on retrospective data) that a baseline PSA in men aged between 40 and 49 years can be used to categorize men into low and higher prostate cancer risk groups.
This new paper (by Weight et al.) reports the results of a long-term, prospective study of 268 randomly selected males, all living in Olmsted County, Minnesota, and all aged between 40 and 49 years of age at time of initial enrollment. (The full text of this article will be freely available on line until November 20, 2013.) As far as we are aware, this is the first-ever report of the long-term follow-up of a prospectively studied group of younger men for risk of prostate cancer.
Since 1990 this group of men has been followed every 2 years (i.e., biennially) with physician visits and evaluations that have included a urologic questionnaire, PSA testing, and a physical examination.
Here are the key findings of the study:
- Average (median) patient follow-up was 16.3 years.
- 192/268 men (71.6 percent) had a baseline PSA of < 1.0 ng/ml.
- 76/268 men (28.4 percent) had a baseline PSA of ≥ 1.0 ng/ml.
- 18/268 men (6.7 percent) were diagnosed with prostate cancer during the follow-up period.
- There were no deaths from prostate cancer in this cohort during the follow-up period.
- For those men with a baseline PSA level of < 1.0 ng/ml
- Risk for a subsequent diagnosis of prostate cancer with a Gleason score of 6 by age 55 years was 0.6 percent.
- Median time to diagnosis of prostate cancer was 14.6 years for the 6 patients diagnosed during the entire follow-up period.
- 0/195 men (0 percent) developed either intermediate- or high-risk prostate cancer during the entire follow-up period.
- For those men with a baseline PSA of ≥ 1.0 ng/ml
- Risk for a subsequent diagnosis of prostate cancer with a Gleason score of ≥ 6 by age 55 years was 15.7 percent.
- Median time to diagnosis of prostate cancer was 10.3 years for the 12 patients diagnosed during the entire follow-up period.
- 2/73 men (2.6 percent) developed either intermediate- or high-risk prostate cancer during the entire follow-up period.
Weight et al. conclude that:
Men (aged 40-49 years) can be stratified with a baseline PSA. If it is below 1.0 ng/ml, there is very little risk for developing a lethal [form of prostate cancer], and as many as 75 percent of men might be able to avoid additional PSA screening until 55 years. Conversely, men aged 40-49 years with a baseline PSA level > 1.0 ng/ml had a significant risk of [prostate cancer] diagnosis and should be monitored more closely.
This study would certainly appear to be a strong validation of the earlier work of Lilja, Vickers, and colleagues that originally suggested (based on retrospective data from Swedish patients) that a single PSA test taken in a man in his 40s can be used to stratify men into prostate cancer risk groups. However, Weight et al. are very careful to observe that
Although we have nearly 20 years of follow-up, this still might not be enough to determine the lifetime risk of [prostate cancer] or risk of death from [prostate cancer].
Filed under: Diagnosis, Risk | Tagged: baseline, Diagnosis, PSA, risk, testing |
THE "NEW" PROSTATE CANCER INFOLINK 
AGGRESSIVENESS OF SCREENING IN THIS STUDY VERSUS THE ERSPC: IMPACT ON EFFECTIVENESS OF SCREENING
For a long time many of us have suspected that the level of screening in the screening arm of the European Randomized Screening for Prostate Cancer Trial (ERSPC) was too loose to detect a substantial portion of the aggressive cases in a timely manner. In the ERSPC, men in the screening arm were given a PSA test just about every 4 years, and a number of deaths from prostate cancer occurred. In this just published US study by Weight and the Mayo Clinic group, screening was every 2 years — twice as often as in the ERSPC, and there were no deaths from prostate cancer with a median follow-up of 16.3 years. Median follow up of 9 years, 11 years, and about 12.5 years has been published for the ERSPC, all well short of the median for the US study, which underscores the result of no deaths from prostate cancer in the US study compared to the European study.
I’m thinking the more aggressive US screening — every 2 years — may be partly or largely responsible for the absence of deaths in the US study. Of course, other factors, such as the median age at entry in the US versus the European study, would also make a difference.
I’m throwing this open for thought.
I’m also thinking about some other insights this US study may provide into the ERSPC results.
Is this (testing before the age of 50) any more useful than doing a test at the age of 50?
Dear Jim:
You are comparing apples not to oranges but to something more like cantaloupes! The men in the study by Weight et al. were something like 20 years younger than the men in the ERSCP, and the4 men in the Goteborg group of the ERSCP were actually tested evgery 2 years.
The only conclusions that can be drawn from the study by Weight et al. are conclusions that relate to 40- to 49-year-olds. It is utterly unsurprising that there wasn’t a single prostate cancer-specific death in their study. Why? Becuase they only identified two patients in the entire study who had intermediate-risk disease at diagnosis, and not a single one with high-risk disease. This confirms the rareity of aggressive prostate cacner in men in their 40s, which we already know to be very low indeed. What will be interesting is additional data from this study by Weight et al. in another 20 years time, when the same group of men have been followed for something like 35 years. At that point, when their cohort of patients are all in the 70s, we may have a much clearer idea of just how accurately a low PSA value in one’s 40s is at projecting any risk for clinically signifciant prostate cancer.
I just hope that Weight et al. can persuade their patient cohort to stay in their study for another 20 years!
Chris:
We don’t have appropriate data to answer that question yet.
I don’t see any usable conclusions here. It is safe to say that a trial would require far more than 268 men. I have access to a biostatistician. Perhaps you can help me frame the question and see how many men would be required for a usable trial? My guess would be probably 100,000 men in trial over 30 years? The end points should be mortality … all cause versus prostate cancer-specific.
So how does this study “support” psa testing for men in their 40s as opposed to waiting until they’re 50?
Tony:
No one’s ever going to do that trial. Within 10 years I suspect the PSA test will be history.
Chris:
Several studies have now shown that a baseline PSA level of < 1 ng/ml in one's 40s is predictive of very low risk for prostate cancer for between 15 and 25 years. By having that early PSA test, one is able to make a decision about whether one needs regular monitoring of one’s PSA or not. Since about 75% of men seem to meet that < 1 ng/ml threshold, it makes it a lot easier for the patient and his doctor to determine who needs regular PSA tests and who doesn't. If one waits until one is 50, then one's risk for BPH starts to climb (along with one's risk for an elevated PSA as a consequence).
Agreed Mike. Maybe sooner we can move past the PSA test. After working on the DoD stuff last month, there are a lot of bright young researchers coming through the pipeline. And working with ASCO and SWOG, the focus is strong to fix the screening issues.