Letters to the Editor on interpretation of data from the ProtecT trial

In September last year, Hamdy et al. published the initial results of the ProtecT trial — a trial designed to compare overall outcomes at 10 years among > 1,600 men diagnosed with low- and intermediate-risk, localized prostate cancer and randomized to treatment by surgery, by external beam radiation therapy, or by active monitoring (a very basic form of active surveillance). The original trial data can be reviewed in two papers published in the New England Journal of Medicine (see here and here).  Our initial comments on the published data can be found here and here.

This week’s issue of the New England Journal of Medicine carries several Letters to the Editor representing differing viewpoints about the interpretation of data from the ProtecT trial. The full texts of all these Letters to the Editor are accessible to any interested reader. Your sitemaster wishes to be clear that his interpretation of the data from this trial is very closely analogous to those expressed by Drs. Klotz, Kibel, Kelleher, Hamdy, Donovan, and Neal in these Letters to the Editor. However, the points made by the other contributors to this discussion are certainly important and will need to be carefully addressed over time.

In interpreting the data from the ProtecT trial, it is critically important for all readers to understand that the “active monitoring” used in this trial was much less sophisticated than the form that most experts in active surveillance would use today, and is much closer to the form of active surveillance used by Klotz and his colleagues when they first started their process of actively monitoring low-risk and some intermediate-risk patients back in the early 1990s. It is therefore hardly surprising that the results of the ProtecT trial — as far as the men undergoing active surveillance are concerned — seem to closely mirror the earliest results from the Sunnybrook series after 10 years of follow-up.

It is also important to appreciate (to Dr. D’Amico’s point in his original editorial comment and his additional comment in the new Letters to the Editor) that the form of active monitoring initially used by Klotz and his  colleagues and also used in the ProtecT trial would not be one that most clinicians would consider to be appropriate for a 53-year-old man initially diagnosed with low-risk or favorable intermediate-risk prostate cancer today. While such a man with low-risk disease may well still be an excellent candidate for active surveillance, we would now expect such a  patient to receive at least a multiparametric MRI and a follow-up mpMRI/TRUS-guided or MRI-guided re-biopsy within 12 months of his initial diagnosis; probably some form of genetic/genomic analysis of his biopsy specimen; and probably also a repeat, annual mpMRI, as well as regular monitoring of his PSA levels and re-biopsies as required based on the results of these tests. None of these modern  forms of monitoring (i.e., only the regular monitoring of PSA levels and necessary re-biopsies) were built into the form of active monitoring used in the ProtecT trial. Active monitoring as a management option has become a great deal more sophisticated over the past 15 to 20 years.

Despite all the subanalysis of the data from this trial, we would remind readers of the basic, bottom-line results reported by Hamdy et al.:

  • “Prostate-cancer–specific survival was at least 98.8% in all groups, and there was no significant difference among the three randomized groups (P = 0.48 by log-rank test).”
  • “There was no evidence that between-group differences in prostate-cancer mortality varied according to age, PSA level, Gleason score, or clinical stage ….”
  • “Deaths from any cause were evenly distributed across the treatment groups ….”

It is also worth remembering that Hamdy and his colleagues had originally expected to see many more men enrolled in the ProtecT trial die of prostate cancer specifically and of all causes during the course of 10-year follow-up in this trial as the numbers who actually did (just 17 deaths from prostate cancer and 169 deaths from any cause over the first 10 years of follow-up).


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