The PSA storm
BMJ 2002; 324 doi: https://doi.org/10.1136/bmj.324.7334.431 (Published 16 February 2002) Cite this as: BMJ 2002;324:431
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I was surprised to find no mention in the debates on PSA screening of
how many men need to be tested (NNT) to identify one prostate cancer or
prevent one related death. I believe that an agreed upon estimated NNT
(or range of NNTs) should be the first step to address this controversy.
For every 1000 men age 55-74 who undergo initial PSA screening and
digital rectal examination, 189 would have PSA greater than 4 ng/mL and 27
of whom would have biopsy-proven prostate cancer.(1,2) If we exclude
patients with minimal disease who require no treatment and those with
incurable advanced disease, there are left 14 patients (50%)(3-5) with
potentially curable, localised disease. About 10 of these patients (70%)
would be cured with prostatectomy(6-8) or radiation,(9-12) assuming cure
as being alive and disease-free 10 years after treatment.
In other words, PSA screening could prevent 10 prostate cancer-
related deaths per 1000 men tested, or an NNT of 100. Whether this NNT is
too high or too low depends on many other factors, such as the risks
associated with PSA testing. However, I suspect that many involved in
this debate have very different NNTs in mind, and hence their apparently
irreconcilable differences.
1. Mettlin C, Murphy GP, Ray P, et al. American Cancer Society--
National Prostate Cancer Detection Project. Results from multiple
examinations using transrectal ultrasound, digital rectal examination, and
prostate specific antigen. Cancer 1993;71(3 Suppl):891-8.
2. Schroder FH. The European Screening Study for Prostate Cancer. Can
J Oncol 1994;4(Suppl 1):102-5; discussion 6-9.
3. Epstein JI, Walsh PC, Carmichael M, et al. Pathologic and clinical
findings to predict tumor extent of nonpalpable (stage T1c) prostate
cancer. JAMA 1994;271(5):368-74.
4. Polascik TJ, Oesterling JE, Partin AW. Prostate specific antigen:
a decade of discovery--what we have learned and where we are going. J Urol
1999;162(2):293-306.
5. Tumor Characteristics of Prostate Cancer Patients. National Cancer
Data Base (NCDB). 1995. Available from
http://www.fac.org/dept/cancer/ncdb/prostat3.html. Accessed 31 August,
2001.
6. Trapasso JG, deKernion JB, Smith RB, et al. The incidence and
significance of detectable levels of serum prostate specific antigen after
radical prostatectomy. J Urol 1994;152(5 Pt 2):1821-5.
7. Zincke H, Oesterling JE, Blute ML, et al. Long-term (15 years)
results after radical prostatectomy for clinically localized (stage T2c or
lower) prostate cancer. J Urol 1994;152(5 Pt 2):1850-7.
8. Pound CR, Partin AW, Epstein JI, et al. Prostate-specific antigen
after anatomic radical retropubic prostatectomy. Patterns of recurrence
and cancer control. Urol Clin North Am 1997;24(2):395-406.
9. Bagshaw MA, Cox RS, Ray GR. Status of radiation treatment of
prostate cancer at Stanford University. NCI Monogr 1988(7):47-60.
10. Zagars GK, von Eschenbach AC, Johnson DE, et al. The role of
radiation therapy in stages A2 and B adenocarcinoma of the prostate. Int J
Radiat Oncol Biol Phys 1988;14(4):701-9.
11. Perez CA, Lee HK, Georgiou A, et al. Technical and tumor-related
factors affecting outcome of definitive irradiation for localized
carcinoma of the prostate. Int J Radiat Oncol Biol Phys 1993;26(4):581-91.
12. Hanks GE, Krall JM, Hanlon AL, et al. Patterns of Care and RTOG
studies in prostate cancer: long-term survival, hazard rate observations,
and possibilities of cure. Int J Radiat Oncol Biol Phys 1994;28(1):39-45.
Competing interests: No competing interests
I consider myself to be reasonably well informed about cancer (a
close relative has cancer). I am aware that the PSA test can yield false
positives and false negatives, so the key question is "what else can be
done to verify, or not, a PSA result?
Competing interests: No competing interests
The PSA Storm
I applaud the courage of Gavin Yamey and Michael Wilkes who dared to
say, “the Emperor has no clothes”. The predictable tidal wave of
invitations to rest upon their own scalpels only serves to confirm how
American vested interests fear their simple truth. The fact is that we do
not know whether PSA testing does more harm or good.
Prostate cancer screening is creeping in by default because no one
has cared to stop it. The entrance fee (PSA-test) is cheap but worth
little more than six free numbers in a lucky draw mail-shot. The final
cost to the patient (and the NHS) can be colossal. Tickets for the
Colonoscopy-show are much more expensive but the rest of the programme is
relatively cheap and effective, and likely to have a happy ending. PSA
screening is a high budget epic that may yet flop. Colon cancer screening
is Oscar material but frozen on storyboard by inadequate resources.
Medico-political woolly-thinkers and urological Holy-grail-spotters
seem to have side-stepped the hard scientific and financial questions and
allowed, or encouraged, the public to select prostate cancer rather than
colon cancer screening. In the UK, suffrage-based medicine simply allows
such practices to flourish. In the USA, PSA-testing is the raw material
for a major dollar-rich industry producing thousands of impotent and
almost-continent men every year. Iconoclasts like Yamey and Wilkes and
fellow urosceptics may take cover.
But PSA screening is not the only regal streaker. Dare I mention MRSA
swabbing of patients but not of staff ? – I guess not!
Robin Brown
cholesterol 6.5, PSA unknown, MRSA +ve (probably)
Surgeon
Surgical directorate,
Daisy Hill Hospital, Newry. N. Ireland
Yamey G, Wilkes M. The PSA Storm. BMJ 2002; 324: 431. (16 February).
Competing interests: No competing interests
Yamey and Wilkes continue to insist that they are the injured parties
in this discussion but continue to use the same tired arguments. They see
conspiracy at every turn and continue to malign those that disagree with
men.
You have called this a DEBATE yet use the podiums that you own to
selectively quote and promote your sad stories of harm and being compared
to Nazi's and others - who by the way also controlled the press outlets
and chose to publish half-truths and exaggerations. Like those cads sixty+
years ago the light of truth and truly free speech opens the eyes to a
public ready, willing and able to make an informed decision when presented
the full story.
A challenge to a true debate on the subject of early detection of
prostate cancer was issued publicly weeks ago (including in the BMJ) and
yet not a single word from either Yamey or Wilkes has been heard. Why? I
personally offered to pay for this true debate (defined by all but
apparently the BMJ as a two sided discussion) out of my own pocket and yet
for weeks all we have been subject to is the same drivel trying to sway
public opinion to believe that these two fine professionals with the only
truth are being savagely attacked by people too stupid to understand that
they are pawns of "a very wealthy and powerful pro-screening lobby that
stands to make money from encouraging men to get tested."
Get off it gentlemen. If you had the power of your opinions and the
strength of your convictions you would not hide behind your corporate
sponsored ivory covered walls and advertiser funded media outlets (which
you conveniently forget to disclose while touting the U.S. citizen tax
supported funding you receive to tell us how we must be protected by you
because we are too ignorant to make an informed decision on our own). Do
the public some good by openly debating two professional colleagues. The
problem is that such a debate would require some professional backbone and
data more recent than 1996. It would also require some dedication to truly
helping men make an informed decision and not simply throwing bombs and
then wrapping yourself in the first amendment.
Instead, you continue to whine and cry foul while basing the motives
of others - the same sleezy tactics you have usedsince day one. Sorry
gentlemen, my six year old does a better job of supporting her decisions
and standing up and supporting her opinion when others disagree.
John Page
Competing interests: No competing interests
This letter concerns The PSA Storm and the letter to the San
Francisco Chronicle criticizing the use of PSA.
The PSA controversy will continue with us until sufficient data paves
a clear way for us on the relationship of PSA and the relative merits of
the modalities used to treat...whatever it is we are treating.
Irrespective, other matters are worth commenting upon in the letter.
In the opera, The Phanthom advises his love that "Hearing is
believing...the truth isn't what you want to see, in the dark it is easy
to pretend, that the truth is what it ought to be...open up your mind, let
your fantasies unwind, in this darkness which you know you cannot fight.
Close your eyes start a journey through a strange new world, leave all
thoughts of the world you knew before." This is not so easy as it may
seem.
Today, it seems, no one has clean hands when it comes to taking a
position on the value of the use of PSA. Agendas are everywhere. The
paradigm, 'elevated PSA, do something', has a rational appeal to our
simplistic thinking that is so often correct. Although benign factors may
be the cause of an elevated PSA, missing a malignancy seems genuinely more
serious. Yet, in the realm of knowing, strong as it is in some
disciplines, we still falter when it comes to the biological sciences.
The early finding of an elevated PSA and the curative removal of the
prostate do not necessarily coincide. Nothing is more disheartening than
to remove a prostate in a young person with seemingly minimal and
localized disease only to have he PSA re-present itself later. What it
demonstrates is not that a lobby has been busy or successful in getting
doctors to use the test in anticipation of offering some modality, but
rather that we are still searching. Doing nothing about the situation is
not doing enough.
Yet, knowledgeable and committed scientists contend that any cancer
at presentation is de facto systemic disease. Here, one hears the call
for work on the causative end. Against this fatalistic philosophy are the
abundance of cases with no evidence of recurrent PSA or prostate cancer
for many years post radical prostatectomy.
The fact that the value of breast mammography is being challenged
presently in no way supports demeaning the use of PSA and its possible
association with early curable prostate cancer. Breast mammography is a
radiological study; PSA is a biochemical test. There are certainly
difference spatially in the function of a cell and the calcification of
cells. One cannot see noncalcified malignant breast cells by mammography.
And that is not what we are trying to see with PSA; we are assuming a
change in cellular behavior at the breaking point. At least this seems to
be the case.
I have had no experience with the 'dominance of the pro-screening
lobby' and my colleagues seem earnest in their contention that a rising
PSA in the face of a biopsy proven malignancy cannot mean spring is around
the corner; these seeds should be considered bad.
What the authors mean that the 'PSA test was unreliable, that it
often picked up innocuous tumours, and that picking up such tumours harmed
men by causing anxiety and by subjecting them to unnecessary cancer
treatments with serious side effects,' defies comprehension. What is
unreliable about an elevated PSA and what do they mean by innocuous
tumours?
A brief window of opportunity is here in which to take a position.
It may not last; governments falter in their promises of health care. It
is unrealistic to expect the British to be interested in assessing the
screening value of PSA; the cost to the Crown would be staggering and as
someone once wrote, England is only a little larger than two times Lake
Victoria. In the same vain, America's promise is beginning to falter,
explaining the sudden rash of new modalities in the treatment of either
benign or malignant prostate disease. The window is to let things alone
and see what works best in the end.
Reflecting, it is worthwhile to muse on Hunter's advice to
Jenner who asked on whether to vaccinate; "Why think," responded Hunter,
"Try the experiment." The world knows the end of that. Rather than
berating one another we should respect differing stances and await the
ultimate assessment. The truth has a way of floating to the top.
Competing interests: No competing interests
Re: PSA screening - what is the NNT (number needed to test)?
The NNT figures given by Dr de Lemos should be taken with a
pinch of salt. The assumption is made that the patients with screening
detected prostate cancer who are selected for treatment will die of
prostate cancer if not treated. This is not necessarily the case,
particularly for the majority who develop the disease in later life. As Dr
De Lemos suggests there is wide uncertainty as to the true NNT. This is
due largely to the uncertainty of the true benefit of radiotherapy and
prostatectomy. Randomised trials were previously difficult due to the long
follow-up period required and firm beliefs of surgeons or radiotherapists
regarding their own modalities. Now randomised trials are difficult due to
increasing pressure towards treatment rather than 'watchful waiting'
Inevitably, with screening more patients will be exposed to the side-
effects of these treatments and the NTP (number treated pointlessly) will
increase.
Competing interests: No competing interests