What the ProtecT study has taught us to date

The Prostate Testing for Cancer and Treatment (ProtecT) trial is being implemented in the UK to evaluate outcomes of three different types of treatment: surgery, radiation, and “active monitoring” in the management of localized prostate cancer. It is a randomized, controlled clinical trial in which enrollees must agree to be managed using any one of the three clinical treatments at random (which would probably prove impossible in the USA today). However, data from this study has already confirmed some expectations based on US experience.

In a newly published report, Moore et al. used data from the ProtecT study to determine the stage and grade of newly diagnosed prostate cancers identified as a consequence of PSA testing and biopsy.

The ProtecT study enrolled 94,427 men, all aged between 50 and 69 years from nine cities in the UK and from randomly selected practices of general practitioners. Men with a PSA level of > 3 ng/ml were offered a prostate biopsy. The age, PSA, stage, and grade at diagnosis of ProtecT participants with cancer were compared with data from unscreened prostate cancer patients aged 50–69 years registered with the UK’s Eastern Cancer Registration and Information Centre (ECRIC).

The results of the study to date have shown the following:

  • The 94,427 enrollees who agreed to be tested represented ~ 50 percent of all men invited to participate.
  • 8,807/94,427 enrollees (9.3 percent) had a raised PSA level.
  • 2,022/8,807 men with an elevated PSA (2.1 percent of all enrollees) had prostate cancer by biopsy.
  • 229/2,022 patients (only 0.24 percent of all enrollees) had locally advanced (T3 or T4) or metastatic cancers.
  • All other patients (1,973/2,022 or 1.9 percent of all enrollees) had clinically localized (T1c or T2) disease.

Within the ECRIC database, over the same time frame, 12,661 cancers were recorded, of which 3,714 were in men aged 50–69 years at diagnosis. However:

  • Prostate cancer cases identified in the ProtecT study had a lower age distribution and PSA level that those registered in the ECRIC database.
  • Prostate cancer cases identified through ProtecT were of significantly lower clinical stage and grade than those in the ECRIC database.

The authors estimate that the introduction of population-based PSA testing in the UK, would increase the incidence of prostate cancer to 2,660/100,000 in men aged 50–69 compared to the current rate of 130/100,000 (a 20-fold increase). They suggest that if just half of the eligible men in the UK accepted PSA testing, the annual incidence of newly diagnosed prostate cancer cases would rise to ~160,000 as compared to the current incidence of 30,000 per year.

The authors conclude that population-based PSA testing “resulted in a significant downward stage and grade migration, and most such cancers were of low stage and grade.” However, they also note that identification of many of these cancers “could lead to risks of over-treatment for some men.”

In an interview with Professor David Neal, the senior author of the report, ABC News reports Dr. Neal to have made a number of additional points, as follows:

  • Although the UK does not offer routine PSA testing as part of standard care, “all men can get the test upon request.”
  • “We’re not trying to in any way stop men coming forward to be tested.”
  • The clinical goal in the UK is to begin to identify high-risk populations of men who should be screened, and to establish which men with prostate cancer need aggressive treatment with radiation, drugs or surgery, and which men can be managed more conservatively.

While The “New” Prostate Cancer InfoLink fully appreciates the wisdom of this clinical strategy, we are also concerned about the importance of identifying prostate cancer in the (admittedly small) subset of men who can be identified with potentially clinically significant prostate cancer at ages younger than 50. We know that these men are potentially at risk for more aggressive forms of disease, and we also know that unless they are diagnosed early, they are at significant risk for prostate cancer-specific mortality by comparison with those diagnosed in their 60s and 70s (when most men are in fact diagnosed with prostate cancer).

It will be many years before the final reults of the ProtecT study are available, and by the time they are available, it is possible that we will have learned enough about how to better identify and manage prostate cancer to make the trial’s results irrelevant. In the meantime, however, what the trial data are showing is that introduction of widespread screening in the UK would have a similar impact on the incidence of low-risk prostate cancer as was observed in the USA in the 1990s, with all of the concomittant risks for over-treatment — particularly in older men with very low risk for clinically significant disease.

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