New draft USPSTF guidance on screening for risk of prostate cancer (the details)

As indicated earlier this morning, the US Preventive Services Task Force (USPSTF) has issued new draft guidance on screening for risk of prostate cancer. Access to all the relevant details is provided below:

The new draft guidance now provides a level C recommendation with regard to screening for men in the age range of 55 to 69 years. The draft recommendation reads as follows:

The decision about whether to be screened for prostate cancer should be an individual one. The USPSTF recommends that clinicians inform men ages 55 to 69 years about the potential benefits and harms of prostate-specific antigen (PSA)–based screening for prostate cancer. Screening offers a small potential benefit of reducing the chance of dying of prostate cancer. However, many men will experience potential harms of screening, including false-positive results that require additional workup, overdiagnosis and overtreatment, and treatment complications such as incontinence and impotence. The USPSTF recommends individualized decisionmaking about screening for prostate cancer after discussion with a clinician, so that each man has an opportunity to understand the potential benefits and harms of screening and to incorporate his values and preferences into his decision.

However, the new draft guidance continues to recommend against screening for risk of prostate cancer among men of 70 years and older (a level D recommendation), stating simply that:

The USPSTF recommends against PSA-based screening for prostate cancer in men age 70 years and older.

The USPSTF has also put up a new, detailed web site that provides complete information for patients and their physicians designed to explain its thinking. This web site includes pages addressing all of the following:

The detailed guidance states clearly that

This recommendation applies to adult men in the general U.S. population without symptoms or a previous diagnosis of prostate cancer.  It also applies to men at increased risk of death from prostate cancer due to race or family history of prostate cancer.

This recommendation does not apply to the use of the PSA test for surveillance after diagnosis or treatment of prostate cancer.

The detailed guidance also includes a specific and appropriate subsection on “Research Needs and Gaps” which, at a first glance, appear to be highly appropriate and accurate.

While there are certainly going to be some who are distressed by the continuing D recommendation for men of 70 years and older, our initial reaction is that the new draft guidance is a vastly improved and much more accurate assessment of the value and role of PSA testing than the guidance issued formally back in 2012, and if nothing else the USPSTF is to be congratulated on the thoroughness of its new review that has led to this set of new recommendations.

17 Responses

  1. Better USPSTF Position, But Still Lack of Understanding

    Thanks very much, as always, for your timely reporting!

    I’m looking forward to reading the extensive details, but at first glance it is encouraging that the Task Force finally recognized that there is a benefit to screening (a mildly positive Grade C, instead of a negative Grade D). Still, their words are in the nature of “damning with faint praise,” and it looks like they have once again grossly over-estimated the harms of screening if active surveillance is adequately appreciated as an option. That is a critical point! They have also apparently under-estimated the benefits of screening.

    The cut-off at 70 is distressing, but, based on their history, not surprising.

    At least this is a draft, and we have a chance to bring this recommendation closer to what it needs to be.

  2. The American Urological Association has already issued preliminary comment on the new draft guidance that appears to be generally positive in nature.

  3. Obamacare Coverage of Screening?

    I believe that a grade C recommendation, if finalized, would mean that screening would be covered as a free test under the Obamacare law. Is that correct?

  4. I would like to hope so, but given the current political chaos about our healthcare system, frankly, who the heck knows?

  5. At 13 years of median followup, a test for statistical heterogeneity in prostate cancer mortality results across ERSPC sites was not statistically significant (p=0.43) (Appendix E Table 5).

    i.e. the null hypothesis that prostate cancer mortality reduction was different in every site from all the others was not rejected. Of course, what they should have tested was whether the prostate cancer mortality reduction was the same as the overall average at every site, which would have rejected Sweden from homogeneity with the overall average.

    Yet another group of MDs who are incompetent at statistics. But as we all know, urologists are more than happy to be supported by incompetent statistics.

  6. Dear Mr. O’Neill:

    If there is one thing that a group of experienced epidemiologists is certainly not going to be incompetent at, it is statistics!

    Your problem is probably with the trial design, which was poor in many ways, and which probably did not set out to measure whether the mortality reduction was the same as the overall average at every site.

  7. National Cohort Differences Among the Countries Participating in the ERSPC

    Chris: I’ve seen Sitemaster’s apt point about the experienced epidemiologists who have been in charge of these statistics. The following provides some more detail and a pertinent link regarding the statistics and is a rebuttal to your point that “Of course, what they should have tested was whether the prostate cancer mortality reduction was the same as the overall average at every site, which would have rejected Sweden from homogeneity with the overall average.”

    If you look at the national figures for the 13 year follow-up and the supporting text, you can see that there were great differences among the participating nations, with some having a much more effective trial design and execution for the purpose of determining whether there was a mortality benefit to screening, and those with more effective and better executed protocols showing superior results. You can get a pdf copy of the report at , including all the published tables.

    Here’s a brief overview from Table 1 from this report:

    – The follow-ups at the published 13 year point differed greatly, ranging from an average (median) of 13.0 years in the Netherlands, Belgium, Sweden and Finland, with 12.6 in Italy and 12.7 in Spain, with Switzerland lagging at 10.2 years, for an average excluding France of 13.0, with France at just 6.4 years at one center and 7.5 at another.

    – The sizes of the national groups of men who were randomized differed greatly among the seven nations with about 13 years of follow-up plus Switzerland at 10.2 years: from 80,379 in Finland, to 34,833 in the Netherlands, to 14,517 in Italy, to 11,852 in Sweden, to 9,903 in Switzerland, to 8,562 in Belgium, and just 2,197 in Spain. France comes in at 79,011 at its two centers, but, as noted above, the follow-up was short. That’s why results were analyzed with France, with its relatively large number of participants, set apart, and then included for an overall view.

    A few other important considerations, among others that could be noted:
    Belgium ran short of funding after its initial screening work, resulting in a less robust trial.
    The screening interval was rather long – 4 years in all nations except Sweden, where it was 2 years, with a 2 year interval more likely to catch especially dangerous cancers in time and therefore reduce the mortality numbers, thereby more likely to show a benefit for screening.

    The effects of “non-compliance” and “contamination” with randomized assignment resulted in a substantial underestimate of the benefits of screening, as has been indicated by published work.

    It is also critical to realize that (1) prostate cancer is generally a disease with a long fuse (but devastating impact for those with serious prostate cancer either from disease burden, mortality, or both), and (2) that follow-up in the ERSPC FROM DIAGNOSIS, even at the “13” year point, was quite short compared with the natural history of the disease: “. Although the follow-up from randomization is 13 years, the median follow-up from diagnosis of PCa is only 6.4 and 4.3 years in the intervention and control arms (data not shown), and previous studies have shown that the natural course of early PCa usually is in the range of 15–25 years21, 22.“ Thus, even though the key follow-up was remarkably short and premature, even with the adverse effects of non-compliance with randomization, and even with the inclusion in the mortality averages of national results where the protocols were weaker, the trial was STILL SHOWING A SUBSTANTIAL BENEFIT FOR SCREENING! (This is in the section Differences Between Age Groups And Centers.)

    These are some of the facts and reasons why it is important to look at individual nation results from the trial and not lump everything together as the best indicator of truth.

  8. According to article on Medscape the previous recommendation against screening was age 75. It has been lowered to 70. Hopefully this will be explained in the documentation for the new “guidance”.

  9. Dear John:

    I haven’t read the Medscape article you are referring to, but the USPSTF’s 2012 recommendation was against screening for all men, regardless of their age, so I don’t know why anyone would think the new guidance had “lowered” the age to 75 years. It is possible that the Medscape article was referring to guidance from other organizations (e.g., the AUA), which (I think) suggests limited value of screening for men of 75 and over.

  10. Impressions of the USPSTF Draft Statement and Supporting Documents

    I have now read the draft statement, which is 16 pages long, and glanced at the Evidence Synthesis attachment, which has a nine page introductory segment plus 216 numbered pages. Whew!

    There is a lot to like in this draft, as well as some concerns I hope the Task Force will address:

    Grade “C”: The move from a grade “D” recommendation to a grade “C” recommendation is critically important and most welcome.

    Active surveillance: The current Task Force, in sharp contrast to the previous Task Force, understands active surveillance, its general role in reducing over-treatment, and the steeply rising trend in choice of active surveillance for appropriate patients. However, the draft document still emphasizes harms of diagnosis and treatment without adequate recognition that active surveillance basically wipes away harms of unnecessary treatment. I hope a lot of us will submit comments to the USPSTF on that. Also, the role of active surveillance as a staging tool to smoke out aggressive cancer that may be stealthy is not appreciated adequately: the Task Force’s faulty view is that there is no good way to assess whether an aggressive cancer is likely. While it’s true there is no simple and quick test, we know now that active surveillance is highly effective in smoking out stealthy aggressive cancer in a timely way, and active surveillance technology is ever-improving. The Task Force needs to grasp this central fact.

    More than just mortality: It is most welcome that this Task Force recognizes and reports the importance of preventing metastasis, a movement beyond a narrow focus on mortality that plagued the previous panel.

    The PLCO trial: This Task Force mostly recognizes that PLCO trial results are not useful in measuring the benefits of screening – a most welcome development. However, it still gets some minor, stray credit in the discussion of screening for African Americans.

    The ERSPC trial: This Task Force leans heavily on the 13-year update of the European screening trial, and, in another most welcome development, appreciates at least somewhat the important differences in protocols and results among the participating European nations. However, my impression is that they are leaning too much on overall results, which dilute the impact of screening due to weaknesses in some nations’ protocols and trial execution. Also, I haven’t yet seen an awareness of the impact of non-compliance with protocols, which has been analyzed in published papers; these papers show an increased impact of screening when only those actually screened and actually not screened — regardless of randomized assignment — are considered.

    Key trials results: Their statement of key ERSPC trial results, especially the number needed to invite to screening to save one life (781 in the 13-year update), will no doubt be widely quoted and noted by doctors, but that number is not put in perspective: there is no indication that the original 9-year report set that number at 1,410, nor that 2 years later it had plummeted to 1,055, with a further sharp drop to 781 in just two more years. Moreover, there is no context provided that a further drop can be expected, that more effective national trials resulted in much steeper drops, and that filtering out effects of non-compliance further enhances the evident effectiveness of screening. I have not seen any awareness that follow-up from diagnosis in the ERSPC is still premature: 6.4 years in the screening arm, and 4.3 years in the control arm (reported in the 13-year results paper). However, last night it was evident that at least one voting member of the panel, Dr. Alex H. Krist, did recognize and appreciate the importance of the sharp decline in screenings needed to save a life or prevent progression to metastatic cancer.

    Discussions with patients whether to screen: I’ll put this in a separate comment as it is so important and lengthy.

    No discussion of use of high-volume centers to reduce harms: Harms of unnecessary treatment can be minimized by active surveillance, and we know that harms of necessary treatment can be minimized by treatment at high-volume centers. I do not see this discussed at all.

    Other concerns: I have some other concerns, but they are lower level, such as an absence in recognizing the role of oncologists in treating prostate cancer and achieving success with cases that are not localized.

  11. Dear Jim:

    A number of your comments about this report seem to address issues that are way beyond the scope of the USPSTF’s responsibilities.

  12. Hi Sitemaster,

    As ever, your comments help me think.

    The “Other concerns” at the end may be what caught your attention in your comment of 7:20 am. On reviewing this, there is a lot of attention in the statement to radiation, which mainly involves radiation oncologists. However, in the “Potential Benefits of Treatment” section that starts on the tenth page, they looked at “three good-quality randomized trials of treatment of localized prostate cancer and nine observational cohort studies to understand the potential benefit of active treatment (radical prostatectomy or radiation therapy … on overall mortality, prostate cancer-specific mortality, and progression to metastatic prostate cancer (3).” They may not be seeing the added benefit that modern oncologists and drug treatment can provide, unless those cohort studies look beyond “localized” prostate cancer.

    This seeming shortcoming is not a key part of this statement on screening, but it does involve important territory related to benefit of treatment against the potential or occurrence of metastatic and lethal prostate cancer, avoidance of which is a key benefit, does it not? I hope to look at those “nine observational cohort studies” to see if they do in fact cover this ground.

  13. No Jim.

    My point was that you are asking the USPSTF to make comments on issues that are way beyond the scope of their responsibilities. It’s not their job to get into the details of how active surveillance can be used to monitor appropriately selected men at risk, any more than it is their responsibility to advise on how the conversation between a patient and his doctor about PSA testing is conducted. It’s also not their job to comment on the outcomes of treatment at different centers. Their task is only to determine whether or not testing of individuals for their risk of prostate cancer is an appropriate medical imperative.

    They have recommended that this is very much a matter of the individual wishes of the individual patient, which I believe to be entirely correct (although I also think this applies to some men of 70+ years of age with a life expectancy of 10+ years). The things that they commented on are relevant to that decision. Most of the things you are criticizing them for not doing are not relevant to that decision. And I am 100% certain (as an example) that the members of the USPSTF are well aware that active surveillance has lower risk for side effects and complications than any form of immediate treatment (but it still has risks, including those associated with multiple biopsies over time).

    You are also asking the Task Force to “put into perspective” the idea that the number needed to screen to save a life in the ERSPC trial will continue to fall, but I have pointed out before that that is not necessarily the case at all, and actually it would be highly inappropriate for the Task Force to make such a projection.

  14. Interesting that the suggested cutoff for PSA monitoring is 70 years … many Viet Nam vets are in this group. My husband, age 75, served two tours in Viet Nam as an infantry officer, and was just diagnosed with intermediate-risk, Gleason 7 (4 + 3) prostate cancer. It was caught due to a rise in his PSA which led to a DRE and biopsy. I didn’t read the full report, but since the government has acknowledged that exposure to Agent Orange — even one visit to Viet Nam by blue water sailors — has been linked to prostate cancer , one would think that that veterans would be specifically urged to continue PSA testing.

  15. Dear KL:

    I completely understand your perspective. However, I also think you need to appreciate that (based on the details of your husband’s case, all of which would be very important) his risk of actually dying of prostate cancer within the next 15 years might be very low indeed — even if he had no treatment whatsoever.

    If you and he want to be able to get a perspective on that, you would need all of the relevant medical data and you could then use the Prostate Cancer Male Life Expectancy calculator on the web site of the Memorial Sloan-Kettering Cancer Center to calculate his risk for prostate cancer-specific death (as opposed to his risk of death from other causes) at 10 and 15 years from now.

  16. Re recommendation of no screening for those 70 and older by USPSTF

    My understanding is that the key reason for the draft (still!) negative recommendation is that this age group was not well studied in the trials, especially the key European trial. The USPSTF tries to be a very data-oriented group, though it is clear that their absence of substantial expertise with prostate cancer has been a severe handicap. Therefore, the absence of good data, such as for those 70 and older in screening trials, effectively puts blinders on the USPSTF. Let’s hope those blinders don’t lead to more blunders, as in the past.

  17. Any Clue as to Why the Final Recommendation on Prostate Cancer Screening Has Still Not Been Released?

    I just checked the USPSTF site and confirmed that the recommendation is still pending! This seems like an unusually long period of review without issuance of a recommendation, but I am not familiar with their track record. It has been about 9 months since the deadline for comments on the draft recommendation.

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