“Toward a rational strategy for prostate cancer screening …”

The heading above is the first part of the title of a paper to be presented by Lilja et al. at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. The data from this study needs to be seen in conjunction with data presented just the other day by Vickers.

Vickers, Lilja, and others from their research group have now spent several years mining data from the 30-year-long Malmö Prevention Project and similar, long-term studies to try to define a new, risk-based model for prostate cancer risk assessment and monitoring. While it would be wrong to say that we now have a well-defined “better way” to think about the use of PSA testing to manage prostate cancer risk, it is certainly true to say that, based on the research from this group, we appear to be much closer to a rational strategy.

At the American Urological Association meeting in Washington, DC this week, Vickers et al. used data from the Malmö cohort to present data on the ability to accurately predict high-risk disease in men aged between 44 and 50 years of age (see AUA abstract no. 986). They had previously reported that there was a strong association between PSA levels measured within this age range and diagnosis of prostate cacner up to 30 years later. In this specific presentation, Vickers showed that:

  • A single PSA test between ages 44 and 50 was “strongly predictive” of prostate cancer-specific mortality at a median of 27 years follow-up.
  • 44 percent of prostate cancer-specific deaths in the cohort occurred in men with baseline PSA levels in the highest 10 percent of the cohort.
  • 42 percent of patients progressing to have metastatic disease occurred in men with baseline PSA levels in the highest 10 percent of the cohort.

Vickers et al. concluded that: (a) long-term risk of prostate cancer-specific mortality could be predicted on the basis of a single PSA test in men < 50 years of age and (b) careful targeting of a small proportion of men with high baseline PSA levels prior to age 50 and the application of an early intervention strategy for such men (with regular PSA tests, careful compliance monitoring, and possibly chemoprevention) might be able to prevent about half of all prostate cancer deaths.

In their paper to be presented in Chicago in a couple of weeks time, Lilja et al. take the logical “next step” by using additional data from the same cohort of men in the Malmö study to describe a long-term prostate cancer risk management strategy. This strategy basically takes a series of steps over time:

  • It is assumed that some men known to be at very high risk for prostate cancer may need an initial baseline PSA test at 40 or younger.
  • All men should get a baseline PSA test (and probably a DRE) between the ages of 44 and 50.
    • If the results of this test shows a PSA value in the top 10 percent, they should be enrolled in an annual PSA testing and risk compliance regimen.
    • A small number of men may well require biopsies and perhaps treatment based on data collected at this time.
  • The remaining 90 percent of men should get a second PSA test (and presumably a DRE) at age 51 to 55.
    • Again, men with a PSA that is significantly elevated (those in the top 10 percent again?) should be enrolled in an annual PSA testing and risk compliance regimen.
  • The remaining 81 percent of men should get a third PSA test (and presumably a DRE) at age 60.

Based on this testing strategy, using intense surveillance of a small proportion of the men with the highest PSA levels at age 44 to 50 years, Lilja et al. state that:

  • Close to half of all prostate cancer deaths deaths could be prevented.
  • Men with lower PSA levels at age 44 to 50, would be re-tested at age 51-55 and at age 60, which is sufficient to capture risk of prostate cancer metastases or death 10+ years in advance.
  • About 50 percent of men would need to have no more than three PSA tests during their lifetime.

Now it seems likely to The “New” Prostate Cancer InfoLink that this strategy will need s0me refinement, and there are always exceptions to every rule, but if one was to generalize this strategy, it looks as though we are talking about a 5-year interval between PSA tests and DREs starting at age 40 for men who show no signal of risk for prostate cancer, with a last test needed at 65 or perhaps 70 years of age for men who continue to show no signal of risk at that time. Men who show a clear signal of risk at any point along the timeline would then be given more intensive surveillance.

Even Dr. Brawley over at the American Cancer Society seems to think that this type of risk profiling and follow-up strategy would be better than what we have today (according to a report on Bloomberg.com)!

Of course the hard part in the application of such a risk management strategy will still be getting men to go in for those early baseline and 5-yearly PSA tests, but at least the test can most certainly be done easily enough — right along with the blood to test cholesterol levels and other general health indicators.

Would we still prefer it if a better test was available? Absolutely, but that test may well be most appropriate if reserved for the men who meet the preliminary risk levels suggested by a 5-yearly PSA test.

11 Responses

  1. Is there information available as to where the “PSA value in the top 10 percent” cutoff levels are? Would it be the same level for all men between 46 and 50, or would it be more specific with a different cutoff for each age in years? And why not apply this strategy starting at an earlier age? I would be interested to test such against my own situation, which was a PSA of 2.5 at 43 years, and a PSA of 4.5 and T3 cancer at 45 years.

  2. Dear Richard:

    (1) I am sure that the publications of Lilja, Vickers, and their research team would contain the data on the top 10% of patients in the Malmo cohort, but that is just one series of patients, and the concept they are proposing needs to be tested in other series of patients.

    (2) Based on the accumulated Lilja and Vickers data, you were at significant risk for prostate cancer at age 43 with a PSA of 2.5 ng/ml, and should probably have had a biopsy at that time (if there was no other good reason for an elevated PSA level, such as a urinary tract infection), which might well have found your cancer earlier. Even if you had had a negative biopsy at age 43, they would argue that you should have started to have annual PSA tests at that point.

  3. Yes, I know that this early PSA reading should have been followed up. It came together with a %free PSA of 13 which is low and should have also been a big red flag also. Unfortunately my doctor did not know how to interpret these numbers. Which I think raises another issue: how do you educate the general doctors to follow a complex set of guidelines and interpret the results correctly?

  4. Family practitioners today are under enormous pressure. It is not reasonable for society to expect them to be expert in the diagnosis and work-up of all of the thousands of different diseases we now know how to manage.

    In retrospect it is easy to say that your GP/FP should have referred you to a urologist immediately, but we also have to accept that prostate cancer is a relatively rare finding in a 43-year-old male. That is why I was asking whether there were any other signals that led to your GP/FP giving you the PSA test in the first place.

    It would be wonderful if we could get better agreement on the indicators for prostate biopsy in men at risk, and consensus on the consequent educational priorities for the primary care community. For men like you, who very likely should have received an immediate biopsy, this is obviously a disturbing issue. On the other hand, if we were to start biopsying every man of 40-50 years of age who had a single elevated PSA level (which can be caused by all sorts of factors that have nothing to do with prostate cancer), we would have a different type of catastrophic problem to deal with.

    Clearly your GP/FP could have sent you to a urologist immediately for further investigation of the results of your PSA and %free PSA tests. Whether s/he should have done so is a more complex question.

  5. Based on the online calculators that I have tried, the chances of me having prostate cancer was more than 30%, based on the PSA and %free PSA test results. Surely that is enough to say that she “should” have referred me to a urologist for further investigation or at least monitoring?

    My doctor did the PSA and %free PSA tests because she wanted me to take DHEA supplements. DHEA is contraindicated in men who have prostate cancer because it can increase testosterone and may have other androgenic effects. She knew enough to do the tests, but not enough to interpret them. I had no idea what the results meant at the time, as prostate cancer had not even entered my consciousness. I did take DHEA for 2 years following my doctor’s advice, only stopping when a subsequent test showed a PSA of 4.5, which was labeled as high on the lab report. I don’t know for sure if the DHEA contributed but I sure wish she had sent me to a urologist from the beginning for further investigation, or at least closer monitoring.

  6. Richard:

    That is fair comment, so now my question is, “Why did she think you needed to take DHEA?”

    If she gave you the PSA and %free PSA tests because she thought you were hypogonadal (had low testosterone levels), got the results that she did, and then still prescribed the DHEA, there are plenty of people who might be willing to argue that her recommended treatment was at least unwise without conduct of other tests to rule out the possibility of prostate cancer.

    We can never know for sure that the DHEA did or didn’t contribute to your prostate cancer, but see (for example) this article from just a few days ago. The treatment of hypogonadal men with DHEA is closely comparable to treating them with testosterone supplements.

  7. My serum testosterone at the time of the first PSA test was 335 ng/dl. So low-normal. Serum DHEA was also low-normal. I was visiting the doctor because I was experiencing low energy/fatigue. She thought that DHEA supplements might help that situation.

    I think she did not really understand how to interpret the PSA results. Not too surprising as it is a complex issue as you have said. But in particular she thought that low %free PSA was good, i.e., she read it backwards. I don’t think she should have been messing around with androgen supplements without a better understanding of prostate cancer issues. On the other hand at least I did get treated 2 years later and maybe the DHEA was not a factor. It could have been worse.

  8. Well … Let’s hope that your primary care doctor now has learned how to read a %free PSA test result … and that your experience has contributed signifciantly to her continuing medical education.

  9. Other details of this study:

    — PSA data are available for 1,167 men; 163 of these died of prostate cancer.
    — 10% (117/1,167 men) had a PSA > 1.5; 44% of these (51/117 men) died of prostate cancer (i.e. 31% of all those who died of prostate cancer).

    So, 112 men with a lower (or not measured?) PSA died of prostate cancer as well.

    Suppose you are able to treat (AS included) these 117 men; you need to find something else for the remaining 70% (112).

    Not an easy task.

  10. Actually, we don’t know if the 163 who died of prostate cancer were from those for whom PSA data are available, or from the total population of 20,000 — or do we?

  11. Wolfram:

    I am having a hard time following your logic, but I have a strong feeling that you are muddling data from different subsets of men out of the total Malmo cohort. I don’t think it will be simple to follow any of this without a full publication (or a detailed poster) to work from.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this: