Prostate-cancer screening: Guideline reflects lack of knowledgeable expert input.

The last guideline on prostate-cancer screening was published in 2014. At the time, the task force approached the Canadian Urologic Association (CUA) and asked that it provide an expert panel of “stakeholders” to provide input.

I was asked to lead this panel. I assembled a group of five knowledgeable individuals. The draft of the guideline was provided to us. We produced a detailed critique. Our critique, which was approximately 1,500 words, was evidence-based and detailed.

We found that the task force guideline utilized only data from a small number of randomized trials and ignored scores of other relevant studies. The analysis of the studies that were reviewed was superficial and the guideline was flawed.

This reflected the fact that the members of the task force, as non-experts, relied completely on a very narrow evidence base, i.e., two large clinical trials: the European Randomized study of Screening for Prostate Cancer (ERSPC), which was clearly positive (i.e., a significant prostate-cancer mortality reduction), and the U.S. Prostate Lung Colon Ovary trial (PLCO). Essentially, the task force concluded that, since one study was negative and one was positive, the outcome was a wash, i.e., no conclusive evidence for the benefit of PSA testing.

We disagreed with this interpretation. There is ample evidence from multiple publications that the PLCO trial was flawed by high levels of contamination (85 per cent of the patients in the control arm received a PSA), resulting in negative results. Further, there were many other relevant studies that were not incorporated into the task force’s deliberations.

To our chagrin, we received no response to our submission. When I inquired, I was informed that the task force’s policy was not to respond to comments or submission; rather, our criticisms were “taken under advisement.” To the best of my knowledge, our critique did not result in any change to the document. As a result, my panel concluded that the request for stakeholder input was an exercise in optics, i.e., so that the task force could claim that this input had been incorporated into the guideline development process. Consequently, our panel resigned en masse prior to publication of the guideline.

Shortly after the guideline was published, I invited the task force to provide a member to speak at a urology conference I was organizing. I was informed that a speaker would be provided only if we could promise that the task force’s guideline would not be discussed (!). The chair of the task force wanted a commitment that we would only address “unmet needs in the evidence.”

It seemed obvious that the real reason was that, as non-experts, no one on the panel had the knowledge base to discuss the topic of screening, and the appropriateness of the guideline, knowledgeably.

The 2014 guideline essentially reiterated the conclusion of the United States Preventive Services Task Force (USPSTF) 2012 guideline on prostate-cancer screening, a completely negative recommendation. The USPSTF guideline was heavily criticized, and as a result of these substantive criticisms and the increasing adoption of active surveillance, the USPSTF modified its guideline in 2016 to a neutral recommendation. There has been no movement to change the Canadian guideline that we are aware of.

In the interim, the field of prostate-cancer diagnosis, early detection and treatment has evolved dramatically. These changes include:

  • Multiple studies confirming the value of imaging prior to biopsy;
  • Maturation of the ERSPC study confirming an increase in mortality reduction with longer follow up, and publication of subsets of ERSPC showing greater benefit in those countries where the study was performed most rigorously;
  • Increasing adoption of active surveillance for low-risk disease, further reducing the overtreatment problem;
  • Increasing incorporation of liquid molecular biomarkers to risk stratify prior to biopsy;
  • Germline testing and molecular profiling to match treatment more appropriately to risk;
  • Improved treatments, including advances in radiation, surgery and energy-based focal therapies;
  • An increased utilization of “risk-based” testing to avoid overdiagnosis.

Further, there is substantial new data on the negative predictive value of a low PSA. This means, for example, that men with a PSA below 1.0 at age 60 don’t require any further testing and can be reassured that their risk of prostate cancer death is virtually zero.

None of the above has been taken into account by the Canadian Task Force on Preventive Health Care, whose guideline remains unequivocally against PSA testing. This guideline is increasingly ignored by Canadian physicians. The CUA Guideline, last published in 2022, is the following:

“The CUA suggests offering PSA screening to men with a life expectancy greater than 10 years. The decision of whether or not to pursue PSA screening should be based on shared decision-making after the potential benefits and harms associated with screening have been discussed. (Level of Evidence: 1).

“For men electing to undergo PSA screening, we suggest starting PSA testing at age 50 in most men (and) at age 45 in men at an increased risk of prostate cancer.”

These guidelines are similar to other regions around the world, including the American Urological Association, American Society of Clinical Oncology, Europe, Japan and Australia.

These recommendations are widely accepted by the urology community in Canada and by family practitioners.

We believe that the task force’s inappropriate guideline reflects the lack of knowledgeable expert input into the deliberations and the decision-making process.

Last year, I was invited, again, to provide stakeholder input into a prostate cancer guideline. I inquired as to whether, if I disagreed with the conclusions of the task force on the new guideline that is expected this fall, I would be permitted to withdraw my name. The task force now does not permit this. In other words, stakeholders are listed as providing input even if their comments are ignored and they disagree with the conclusions.

It seems the task force has learned at least this – do not permit ‘stakeholder’ resignations – from its previous experience!