Will we ever be able to prove the value of screening for prostate cancer?

The results of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), which have been published today in The Lancet, offer us some interesting insights into whether we will ever, actually, be able to prove that screening men for risk of prostate cancer reduces the risk of prostate cancer-specific death.

The full text of the results of UKCTOCS are available on line in this article by Jacobs et al. No one is going to suggest that this trial wasn’t well planned and well conducted. And in the end it seems to have demonstrated that screening women of 50 to 74 years of age does, in fact, lower their risk of dying of ovarian cancer by some 20 percent (once prevalent cases, i.e., the cases found at the time of initial testing) were excluded — even though the primary endpoint of the trial was not met because of a trial design decision made many years ago.

It is very important to understand the importance of the exclusion of deaths of women diagnosed after an initial screening test. There is a high likelihood (at least in ovarian cancer) that you are not going to be able to prevent a death from a cancer like this that is found on an initial screening test.

So why is any of this relevant to the question of screening of prostate cancer?

Well, here’s why:

  • Between June 1, 2001, and October 21, 2005, UKCTOCS invited > 1.24 million women to participate in the trial
  • They successfully recruited 205,090 women, and 202,638 women were actually randomized in a 2:1:1 format to either no screening or to one or other of two forms of screening for risk of ovarian cancer.
  • The final cohort of women eligible for analysis at the end of the study numbered 202,546 ( or > 99.9 percent of the women randomized, which is a remarkable retention rate).
  • The two different forms of screening had similar levels of effectiveness in identifying women at risk for ovarian cancer (although one was slightly better than the other).
  • The UKCTOCS investigators followed their patients for a median of 11.1 years.
  • At the predetermined trial endpoint (December 31, 2014), 649  of the women screened (0.32 percent) had died of ovarian cancer: 347 in the no screening group and 302 in one or other of the screening groups.
  • Most of the non-prevalent ovarian cancer-specific deaths occurred in years 7 to 14 of trial follow-up.

Now prostate cancer is about 11 times more commonly diagnosed (prevalent) than ovarian cancer. Here in America, as of 2015,

  • There are about 138 new cases of prostate cancer diagnosed per 100,000 men per year.
  • There are about 21.4 prostate cancer-specific deaths per 100,000 men per year.
  • The percentage of men with a diagnosis of prostate cancer who survive for 5 years after diagnosis is 98.9 percent.

By comparison,

  • There are about 12 new cases of ovarian cancer per 100,000 women per year.
  • There are about 7.7 ovarian cancer-specific deaths per 100,000 women per year.
  • The percentage of women with a diagnosis of ovarian cancer who survive for 5 years after diagnosis is just 45.6 percent.

So even though many more men are diagnosed with prostate cancer each year, it takes much, much longer for those men to actually die of prostate cancer (or even to progress to having metastatic disease).

If the goal of a well-designed screening trial in America was to measure the impact of any screening test (however good) among men of 45 to 74 years of age on risk for prostate cancer-specific mortality, we might reasonably expect that it would take at least 20 years of follow-up and more like 500,000 enrolled patients before we got an answer. And there’s a strong possibility that the answer might still not be definitive at the end.

Having said that, we should point out that we are still waiting (with somewhat bated breathe) for any data whatsoever from the UK’s Cluster Randomized Trial of PSA Testing for Prostate Cancer (the so-called CAP trial). We discussed this trial on this web site back in 2014. As of June 2013, the trial had enrolled a total of 416,387 eligible men — 196,474  were randomized to the PSA screening cohort and 219,913 men were randomized to the control group. At least the number of men would seem to be of the right order of magnitude!

One Response

  1. Excellent . Nice to see collaboration having positive impact!!

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