THE "NEW" PROSTATE CANCER INFOLINK

We have frequently referred to an ongoing trial in the UK known as the ProtecT trial. That trial is comparing the effectiveness and safety of surgery, radiation therapy, active surveillance as treatments for well-characterized men diagnosed with localized prostate cancer … but there is something else important we hadn’t realized …

The ProtecT trial has already completed enrollment of just under 95,000 patients … but to be able to enroll those patients, the study managers needed to be able to identify every potential candidate they could find, and in doing this they were able to carry out another, associated study — the so called “Cluster randomized triAl of PSA testing for Prostate cancer” or CAP trial. This trial is not listed on ClinicalTrials.gov, but information is available on a similar international database known as the ISRCTN Register.

A recently published paper by Turner et al. in the British Journal of Cancer has just provided us with detailed information on this trial … which will be the single largest and, seemingly, the best study (at least to date) of whether prostate cancer screening through the use of PSA testing can truly affect risk for prostate cancer mortality.

Between 2001 and 2007, the CAP study randomized several hundred general practitioner (GP) practices in many geographical areas of the UK (the “cluster” units) into the trial and then approached each practice to see if it would agree to participate. The practices were randomized into one or other of two groups:

• The population-based PSA testing or “intervention” group (within which all men aged between 50 and 69 years of age attending the practice would be invited to undergo PSA testing)
• The “standard care” or “control” group (within which all men aged between 50 and 69 years of age attending the practice would receive “standard care”, i.e., no PSA testing unless there was good clinical reason for such a test)

Here are the results of this study to date:

• 911 GP practices in the UK were initially randomized.
• Of these 911 practices
  • 52 were excluded because because of the absence of matched intervention or control practices in the area.
  • 42 practices randomized to the intervention group were ineligible.
  • 32 practices randomized to the control group were ineligible.
  • Another 212 practices refused to participate for a variety of reasons.
• In the end, 573 GP practices ended up enrolling eligible patients into the trial.
  • 271/573 practices were randomized up front to enroll patients into the intervention arm.
  • 302/573 practices were randomized up front to enroll patients into the control arm.
• These 573 GP practices then enrolled a total of 416,387 eligible men into the screening trial through to June 2013.
  • 196,474 men were randomized into the intervention group (based on their GP’s practice).
  • 219,913 men were randomized into the control group (based on their GP’s practice).

As anyone familiar with the data from the PLCO and ERSPC trials will be aware, the CAP trial has therefore enrolled a truly massive number of patients from a very large number of trial centers, and all of these men were either screened or not screened according to a single protocol in a nation in which frequent PSA testing has been less than commonplace, thus lowering the risk for the types of non-compliance and contamination seen in the PLCO trial and eliminating entirely the variances in screening processes observed from country to country in the ERSPC trial.

For purposes of comparison, the PLCO trial here in the USA enrolled just 76,693 men at 10 study centers, and the ERSPC trial in Europe enrolled 162,243 men (of whom > 70,000 were enrolled in Finland).

How is the CAP trial connected to the ProtecT trial previously mentioned? All men diagnosed with prostate cancer as a consequence of their participation in the intervention arm of the CAP  study were immediately potential candidates for enrollment in the ProtecT trial, thus facilitating the prompt identification of the tens of thousands of men needed to complete enrollment in ProtecT.

The primary and secondary outcomes of the CAP trial are as follows:

• The primary outcome is “definite” or “probable” prostate cancer-specific mortality at a median follow-up of 10 years. This is projected to occur in 2016.
• Secondary outcomes include
  • All-cause mortality at a median follow-up of 10 and 15 years
  • “Definite” or “probable” prostate cancer-specific mortality at a median follow-up of 15 years
  • Disease status and staging
  • Cost-effectiveness

Clearly it is going to be a little while before we know the primary result of the CAP trial — but not that long, and we are horrified that we weren’t aware earlier that this study was ongoing. It does seem to us that this trial is both large enough, straightforward enough, and robust enough to finally answer the outstanding question of whether PSA testing can actually be used to screen men of 50 to 69 years of age for risk of prostate cancer. This won’t help men under 50 years of age who may be at high risk for other reasons, but if the CAP trial can finally resolve the fundamental question that has not been effectively resolved by either the ERSPC or the PLCO trials, that would be a major step forward, most particularly for the 50- to 69-year-old men who are by far the largest at-risk group for a diagnosis of prostate cancer.

Turner and her colleagues write that the CAP trial is

powered to detect an overall prostate cancer mortality rate ratio of 0.87 (13% relative reduction). Reductions in prostate cancer mortality of  the order of 15-20% are likely to be important to the [National Health Service].

This trial could never have been done in America, and it could probably only have been done in a nation with a very large population, a nationalized healthcare system, and a sophisticated GP-based health management system. We congratulate all the investigators and all of the tens of thousands of clinicians and participants who must have worked closely together to make this study possible … and not least Cancer Research UK and the UK Department of Health who committed to the funding for a study of this size.

The “New” Prostate Cancer InfoLink would also like to thank Dr. Emma Turner of the University of Bristol for so promptly responding to our request for a full-text copy of this very important paper.

Filed under: Diagnosis, Risk | Tagged: mortality, PSA, risk, screening, trial |