• The latest on the PSA test and prostate cancer mortality

    I drafted the following modest post before the U.S. Preventive Services Task Force USPSTF released its latest recommendation on the PSA test, which does not deviate from its draft recommendation. Sharon Begley has done fantastic reporting on the issue. And you’ll find a good post at The 141.

    In a NEJM editorial, Anthony Miller tries to make sense of the contradictory results from two recent studies of the PSA test.

    After 11 years of follow-up in the European Randomized Study of Screening for Prostate Cancer (ERSPC), Schröder et al. report in this issue of the Journal that there has been little change in the apparent benefit of screening men for levels of prostate-specific antigen (PSA), as compared with an earlier report. Both studies showed a relative reduction of 21% in the rate of death from prostate cancer in the screening group, as compared with the control group. This reduction was achieved after considerable use of resources: in order to prevent one death from prostate cancer at 11 years of follow-up, 1055 men would need to be invited for screening and 37 cancers would need to be detected. Only in the Netherlands and Sweden was the between-group difference statistically significant []. No significant between-group difference in all-cause mortality was noted.

    In a similar update on prostate-cancer mortality in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial  investigators reported no significant change from the findings of the earlier study. Thus, regarding PSA screening, the negative findings of the PLCO trial and the positive findings of the ERSPC are unchanged. […]

    What the PLCO trial seems to show is that adding organized screening to opportunistic screening will result in no benefit and many adverse effects. These effects include false positive screening tests, unnecessary biopsies, overdiagnosis, and impaired quality of life.

    In much of the rest of the editorial, Miller explains some of the differences between the two studies that might explain the divergence of results. In light of these differences, he concludes,

    We are left with an unsatisfactory situation, in which many practitioners will think there are insufficient data to recommend abandoning PSA screening for prostate cancer. However, the findings of the PLCO trial are more applicable to the situation in the United States, since the ERSPC was conducted in a largely PSA-naive population. Therefore, an intensification of PSA screening would be unwise, and I think it would be advisable to follow the [] recommendations of the U.S. Preventive Services Task Force.

    The ERSPC study is here. The PLCO study is here.


    • Do you have any idea what the data are on death from prostate CA AFTER 11 years? In my experience a lot of people with bad outcomes from prostate cancer have them around 10-15 years after diagnosis. But I don’t know what the real numbers are. This might be part of the problem with the current data as it is reported and the contradictions.

      Also – I have seen a lot of reports about “unnecessary biopsies” but isn’t the main problem unnecessary surgery and treatment? The complication rate of biopsy is real but it is low, and while PSA has a rough correlation with tumor grade it is certainly not strong.

    • “Doctor, could you inform the jury as to WHY you did not order that PSA test?”

      “The studies do not show that the test leads to better outcomes.”

      “Is it possible that if you had done the test, that earlier treatment could have been offered to my client, before the cancer had spread? Is it possible?”
      I agree, the test is statistically useless, but to a malpractice attorney, it’s still a goldmine.

      • I have a forthcoming post on this very point. 🙂 or really 🙁

      • The Merenstein case (which I assume Austin is going to discuss) was a pretty prominent example of exactly this problem.

        Merenstein was a resident who followed USPSTF recommendations and did not recommend PSA for a patient (after discussing the downsides with him). The patient went to another doctor, was given a PSA test without his knowledge, and was found to have cancer. The patient sued Merenstein and his residency, and I imagine that this suit has influenced the practice of more than a few physicians.

        Evidently, following evidence-based recommendations does not protect physicians from lawsuits, so of course they will give the PSA test. This is why there need to be malpractice protections for physicians who follow evidence-based practices.

    • This debate is an excellent example of the difficulties of putting so-called “evidence-based medicine” into practice.

      First, in the real world, many studies produce contradictory results. In part, this is because of things like publication bias and multiple comparisons, but it’s also because it’s very difficult to achieve the sort of controlled experimental conditions that lab scientists can attain. As Miller notes in his editorial, this is an “unsatisfactory” situation, but it’s also hardly uncommon. In the end, Miller argues that the PLCO trial’s results are more applicable, but this is a nuanced call, and it’s easy to imagine that many other equally qualified observers might go the other way.

      The second point is that our evaluations of medical interventions often end up involving a number of different factors that can’t be easily compared: we judge a treatment to be positive not just on the basis of treating the underlying disease, but also because of cost, side effects, drug interactions, ease of transportation and storage, etc. Miller makes this point by claiming that “This reduction was achieved after considerable use of resources” for the ERSPC study. Of course that’s a legitimate point of view, but again others can also legitimately disagree. There’s no “evidence” that can possibly resolve such a dispute, because it’s really an argument about values.

      Of course I”m in favor of “evidence-based” medicine, and I don’t think that there is really anyone out there who would disagree with that. But I also think that the data from clinical trials and epidemiological studies tends to be a lot murkier and problematic than what one might garner from just reading a textbook, and often the evidence fails to produce the sort of bright line that naive proponents seems to think is the usual result.

      By the way, this is EXACTLY the sort of thing that will re-ignite the cry of “death panels”. Let’s see just how long that takes!

    • A routine insurance application found a PSA over 10.1, a follow-up found it over 16, by surgery it was even higher. My husband was only 56. I cannot imagine just letting that go. Who would?