And back to the screening controversy, yet again …

Four very recent articles and presentations have addressed issues relevant to the use of the PSA test in testing/screening for risk of prostate cancer.

An extremely detailed article by Roth et al. in this week’s JAMA Oncology has used sophisticated modeling techniques to examine the economics of testing/screening for and then treating (or just monitoring) prostate cancer.

We’re not going to get into the details. For those who are interested, the entire article is accessible on line. Basically, what Roth et al. showed, by looking at 18 different possible ways of using PSA to test for risk of prostate cancer, is that only the most conservative strategies, when combined with much higher than current use of conservative management strategies like active surveillance and watchful waiting, would have any really significant impact on the costs associated with PSA testing. The conservative forms of management that would achieve significant economic impact would lead to men getting a biopsy and early treatment only when their PSA was > 10 ng/ml. We suspect that that might not be one of the world’s better ideas! This article is also discussed on the Medscape web site.

Two presentations at the recent annual meeting of the European Association of Urology (EAU) in Munich, Germany, were focused on the increased risk that men in the USA are now less likely to get diagnosed early when they are at high risk for clinically significant prostate cancer (because of the guidance from the U.S. Preventive Services Task Force). The papers are both discussed in another article on the Medscape web site.

One of these two presentations, by Deepansh Dalela and colleagues from the Henry Ford Hospital in Detroit, suggested that men aged 75 and older (and particularly the otherwise healthy men of that age group) were 20 percent more likely to be diagnosed with high-risk prostate cancer (cT1–T3NxM0) in the 3 years after 2008 than the 3 years before (odds ratio [OR] = 1.20; P < 0.01), and were 34 percent more likely to be diagnosed with metastatic disease (P < 0.01).

The second presentation, by Christopher Meyer, from Brigham and Women’s Hospital in Boston, was focused on the risk for a similar impact in younger men. Meyer and his colleagues showed that there had been a small decline in the use of the PSA test by urologists over the period 2010 to 2012 (from 38.7 to 34.5 percent; OR = 0.34; P = 0.089). However, among primary care physicians, who are the physicians most likely to be giving younger and otherwise healthier patients an initial PSA test, there had been a far larger decrease (from 36.5 to 16.4 percent; OR =0.43; P = 0.009).

Finally, in another presentation at the annual meeting of the EAU (again reported on Medscape), Hugosson and colleagues provided an 18-year update to the data from the Göteborg screening trial in Sweden.

Initial results from this trial had shown a 44 percent reduction in prostate cancer-specific mortality at a median 14 years of follow-up, as originally reported by Hugosson et al. in Lancet Oncology back in 2010. With an additional 4 years of follow-up, the benefit has now fallen from 44 percent to 35 percent. This is a finding that The “New” Prostate Cancer InfoLink had been expecting.

In his presentation, Dr. Hugosson argued that this drop in the mortality benefit was a consequence of the ending of the screening process when men in the trial reached the age of 70 years. However, that may be a rather controversial conclusion. There may simply be a waning benefit from PSA testing over time (which is certainly what researchers at the Memorial Sloan-Kettering Cancer Center seem to believe, based on their current guidance for PSA testing).

What was clear from Hugosson’s presentation was that, at a median of 18 years of follow-up,

  • Detection of prostate cancer (i.e., overall incidence) was higher in the screened group of men.
    • 9.7 cases per 1,000 person-years in the screened group
    • 6.5 cases per 1,000 person-years in the control group
    • Hazard ratio [HR] = 4.5
  • Prostate cancer-specific mortality was lower in the screened group of men
    • 0.51 per 1,000 person-years in the screened group
    • 0.79 per 1,000 person-years in the control group
    • HR = 0.65
  • Men with less education derived more benefit from screening than those with more education.

As we always remind readers, it is important to appreciate that the Göteborg trial was carried out in a cohort of 20,000 men among whom there had been almost no use of the PSA test to assess risk for prostate cancer prior to initiation of this trial. All men with a PSA level of 2.5 ng/ml or higher were referred for a biopsy in this trial, so the likelihood of finding low- and very low-risk prostate cancers (in addition to clinically significant disease) was high.

9 Responses

  1. Let me know when a better test is available. My PSA rises were ignored and I was put on watchful waiting. … Ask me about the operations and therapies I have utilized to deal with my metastatic disease. The PSA should be used an indicator that additional investigation is worthy of consideration.

  2. Dear David:

    I am sorry to hear about the progression of your disease over time. However, if your PSA was rising and your doctors didn’t investigate why, that’s not the fault of the PSA test. Apparently the test was sending quite a clear signal of a potential problem!

  3. It seems to me that we are throwing out the baby with the bath water.

    Just because discrete PSA tests down add much clinical or financial value to screening efforts doesn’t mean that men shouldn’t have multiple (3 or 4) readings taken at spaced internals of 6 months to 1 year to establish pre-treatment patterns of fluctuation (PSA kinetics) that might provide a very useful benchmark against which to evaluate treatment outcomes should that be necessary.

    This is based on the recognition that patterns of variation, as much or perhaps more than absolute values, are important clinical outcome measures.

  4. Dear pfadtag:

    There is actually a lot of data that clearly indicate that in most cases short-term PSA kinetics are really pretty meaningless. They can be useful in a small subset of patients with aggressive disease in whom the PSA is rising fast and consistently, but that really is a small subset of men. For most men, the key question is when to give a patient a biopsy. Newer tests like the Prostate Health Index or phi test and the 4KScore test are much better at helping to determine whether a biopsy is needed than the PSA test.

  5. Unfortunately, I fall into that small sub- group of men whose cancer continued to grow aggressively after both surgery and radiation treatment.

    Glenn Tisman’s recent article on PSA,variability made the interesting point that some cancers seem to have a characteristic growth pattern which can serve as a indicator of the effectiveness of treatment. These patterns are particularly apparent when PSA data are graphed in a semi-log format which is known in my research tradition as celeration charting. When data are graphed in this way it is possible to see changes in the rate of change over time by carefully inspecting the graph, as well as by calculating measures such as doubling time and specific growth rate.

    Cancer is a biological process and even though it is an aberration of normal cellular growth it still displays a type of internal logic which can be revealed through a systematic analysis of its growth patterns. At least that is one of the lessons I have learned do far by examining my own data set and several dozen that have been shared with me by others who are trying to make sense out of patterns of variation that seem to be totally chaotic.

  6. Dear pfadtag:

    What you say is true, but there are two utterly different things going on here:

    (a) The use of PSA data to determine whether a diagnostic biopsy is needed (at which PSA data over time are, frankly, not very good, because PSA levels can be rising for all sorst of reasons)

    (b) The use of PSA data over time to determine whether and how fast there may be a disease recurrence — at which PSA data are certainly better but still far from perfect.

    While the retrospective plotting of PSA data may help to explain what has been happening in either case, the prospective plotting of such data still leave a very great deal to be desired, and we are getting very close to having much better tests to use to assess risk in both situations. Some of the developers of such tests would argue we are already there.

  7. Exactly the point I was trying to make with my baby and bath water analogy.

    Don’t demonize PSA testing just because it has been misused as a screening instrument.

    As a surrogate measure of underlying tumor activity it is imperfect but often it provides the best data rountnely available to monitor treatment outcomes.

  8. Dear pfadtag:

    As far as I am aware, no one (not even the USPSTF) is “demonizing” the use of the PSA test as a method for monitoring the outcomes of treatment for prostate cancer. Some people, however, have been and are “demonizing” the PSA test as a mass, population-based screening tool (and there is a degree of justification for this if one then rushes every patient with a PSA of > 2.5 ng/ml into a biopsy suite).

  9. I think the Roth et al. article’s really significant finding is that you get reasonable cost-effectiveness ratios of PSA testing if you use active surveillance in low-risk cases a lot, with ratios particularly good if this is combined with fairly lengthy intervals between PSA tests (e.g., 4 years). These strategies dominate the strategies that use a 10.0 threshold for biopsies.

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