Platinum Priority – EditorialReferring to the article published on pp. 530–539 of this issue

Screening for Prostate Cancer: Can We Learn from the Mistakes

of the Breast Screening Experience?

Michael Baum *

University College London, Division of Surgery, London, UK

In the days when I had the pleasure of teaching young

undergraduates, I would always start by explaining what to

me was the self-evident truism that the only meaningful

outcome measures in the practice of medicine were

improving the length and quality of our patients’ lives.

All other measures are surrogates that may or may not

translate into length of life (LoL) and quality of life (QoL).

When I then asked them why we screened for cancer, the

inevitable answer was, ‘‘To catch it early, sir.’’ ‘‘Wrong,’’ I

would shout in mock fury, ‘‘catching it early is a surrogate

end point that may or may not translate into improvements

in LoL and QoL.’’

The European Randomised Study of Screening for

Prostate Cancer (ERSPC) that involved 182 160 men was

first published in full in 2009 [1] and demonstrated a 20%

relative risk reduction in prostate cancer (PCa) deaths

associated with an almost 60% increase in the apparent

incidence of the disease in the screened group. Translating

the relative numbers into absolute values, you would need

to screen 1410 men for 10 yr to avoid 1 cause-specific death

and to incur the cost of the overdiagnosis or overtreatment

of 48 men, with no detectable difference in all-cause

mortality. A very well-conducted study with large numbers

recruited convinced me, as a purist, that there was no

evidence that this intervention improved LoL or QoL.

In this issue of European Urology, the Rotterdam section of

the ERSPC breaks ranks and describes its own results [2]. The

first question I ask myself is whether this provides added

value to the analysis of the totality of the patients in the

ERSPC. Is there any a priori belief that Rotterdam men

behave differently or develop more aggressive phenotypes

of the disease? I think not. Has there been a test for

heterogeneity among the eight national groups contributing

to the overall outcome, showing Rotterdam as an outlier? I

think not. So let’s see if anything new emerges.

The sample size is now only 42 000 [2], give or take, but

the median follow-up is 13 yr, almost 4 yr longer than in the

initial publication [1]. The relative risk reduction in cause-

specific mortality is still 20% overall; however, if you

confine the analysis to the 55–69 age group and then apply

a ‘‘fudge factor’’ correction for noncompliance, you can

boost your results to a magnificent level of 33%.

One then has to ask whether the subgroups of ages

55–69 versus 70–74 were predetermined in the statistical

plan. If so, then an alert must go out that screening the

70–74 age group is associated with a 14% excess of PCa

deaths. Furthermore, I cannot believe that you can correct

for noncompliance because of the inherent ‘‘attendance

bias,’’ one of the cornerstones of screening theory. On the

down side, the Rotterdam study confirms massive overdi-

agnosis, with nearly double the numbers of PCas in the

study arm than in the control arm. I then set about

searching for all-cause death. There is no mention of this in

the text, but the devil is in the detail, and the detail can be

found in Table 3 [2]. All-cause deaths after four screening

rounds amounted to 771 in the screened arm versus 483 in

the control arm! My reaction to this paper was that it

corroborated the initial results of the whole trial after more

mature follow-up, yet the conclusions of the authors

provided a new spin when they stated that PSA screening

is ‘‘hampered by the inability to identify all men at risk of

developing a potentially aggressive or deathly PCa.’’ True,

but it follows that even if we could identify such men who

are programmed to produce such aggressive cancers, these

would be all the more likely to slip through the screening

net and appear as ‘‘interval’’ cases.

E U R O P E A N U R O L O G Y 6 4 ( 2 0 1 3 ) 5 4 0 – 5 4 3

avai lable at www.sciencedirect .com

journal homepage: www.europeanurology.com

DOI of original article: http://dx.doi.org/10.1016/j.eururo.2013.05.030.* University College London, Division of Surgery, 2 Cotman Close, London, NW11 6PT, UK.E-mail address: michael@mbaum.freeserve.co.uk.

0302-2838/$ – see back matter # 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

I am not a urologist, but I know a fair bit about screening

for cancer. I was one of the architects of the National Health

Service Breast Screening Programme (NHSBSP) in the

United Kingdom in the late 1980s and also have enjoyed

the privilege of acting as independent chairman of the

Prostate Testing for Cancer and Treatment (ProtecT) trial of

PCa screening in the United Kingdom for the last 12 yr [3].

I was also one of the first to break ranks with the NHSBSP as

emerging data started to suggest that breast cancer screening

was failing to live up to its promise. Most recently, I published

a paper in the BMJ in which I returned to basics and posed the

question in the introduction of the editorial, ‘‘Does screening

for breast cancer improve LoL and or QoL?’’ The answer was a

resounding no [4].

If we are not to repeat the errors of the past, then all

cancer-screening trials must be reported using absolute

numbers, numbers needed to screen to avoid a cause-

specific death, all-cause mortality, and some measure of

QoL. Impotence and incontinence might be good surrogates

for the latter.

Some biostatisticians get very cross with me when they

argue that the trials were not powered to determine any

impact on all-cause deaths. Yet hundreds of thousands of

men have been randomised in screening trials, so if the

signal has been lost in the background noise, it must be a

very small signal. If that is indeed the case, there is the issue

of opportunity costs when the same money might be used

with greater wisdom to save more lives.

I am confident that the ProtecT trial will not repeat the

mistakes of the past.

Conflicts of interest: The author has nothing to disclose.

References

[1] Schroder FH, Hugoson J, Roobol MJ, et al. Screening and prostate

cancer mortality in a randomised European study. N Engl J Med

2009;360:1320–8.

[2] Roobol MJ, Kranse R, Bangma CH, et al. Screening for prostate

cancer: results of the Rotterdam Section of the European Ran-

domized Study of Screening for Prostate Cancer. Eur Urol 2013;

64:530–9.

[3] Lane JA, Hamdy FC, Martin RM, Turner EL, Neal DE, Donovan JL.

Latest results from the UK trials evaluating prostate cancer screening

and treatment: the CAP and ProtecT studies. Eur J Cancer 2010;46:

3095–101.

[4] Baum M. Harms from breast cancer screening outweigh benefits if

death caused by treatment is included. BMJ 2013;346:f385.

http://dx.doi.org/10.1016/j.eururo.2013.05.053

Platinum Priority

Reply from Authors re: Michael Baum. Screening forProstate Cancer: Can We Learn from the Mistakes of theBreast Screening Experience? Eur Urol 2013; 64:540–1

Screening for Prostate Cancer: We Have Learned and Are

Still Learning

Monique J. Roobol a,*, Ries Kranse b, Chris H. Bangma a,Suzie J. Otto c, Theo H. van der Kwast d, Leonard P. Bokhorst a,Harry J. de Koning c, Fritz H. Schroder a

a Erasmus University Medical Center, Department of Urology, Rotterdam, The

Netherlands; b Comprehensive Cancer Center, Rotterdam, The Netherlands;c Erasmus University Medical Center, Department of Public Health, Rotter-

dam, The Netherlands; d Erasmus University Medical Center, Department of

Pathology, Rotterdam, The Netherlands

In the days when we had the pleasure of being young

undergraduates, we learned one important thing: The most

important question in medicine is not what the doctor

wants or thinks is best for the patient but rather what the

patient wants or thinks is best for the patient. The duty of

the doctor is to guide the patient through the best available

evidence so the patient can make a choice about what is best.

That said, we greatly appreciate the thoughtful words of Dr.

Baum on the issue of prostate cancer (PCa) screening [1]. The

goal of cancer screening is, as is correctly stated, not to catch

the disease early. On the contrary, detecting the disease early

and hence being a cancer patient for a longer period is one of

the most important issues in evaluating the harms and

benefits of cancer screening. The European Randomized

Study of Screening for Prostate Cancer (ERSPC; http://

www.erspc-media.org/erspc-background/) has PCa mortali-

ty as a main end point. However, length of life (LoL) and,

perhaps even more important, quality of life (QoL) are also

end points extensively studied within ERSPC [2].

Starting with PCa mortality, Baum refers to our first

paper published in 2009 in the New England Journal of

Medicine [3]. Looking at the number needed to invite (NNI;

1410), one could conclude that it is not impressive enough

to consider PCa screening as a way of increasing LoL. There

is, however, more than meets the eye, and more published

data from the ERSPC are available. The results published in

2009 reported on PCa mortality at 9 yr of follow-up. At that

time, only 15% of the study population of both arms had

died. At the 11-yr follow-up report [4], the NNI decreased

to 936, with 20% of the study population having died. In

the current report on the Rotterdam section, with 13 yr of

follow-up (and 25% of men having died), the NNI

decreased to 392 [5]. This shows that the NNI is heavily

dependent on the proportion of participants that reached

the end point. The true NNI can be given only if all

participants pass away.

For now, to be able to make assumptions about the true

effect of screening on a population-based level, we have to

DOIs of original articles: http://dx.doi.org/10.1016/j.eururo.2013.05.030,http://dx.doi.org/10.1016/j.eururo.2013.05.053.* Corresponding author. Erasmus University Medical Center, Depart-ment of Urology, PO Box 2014, 3000 CA Rotterdam, The Netherlands.E-mail address: m.roobol@erasmusmc.nl (M.J. Roobol).

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