Reviewer's report
Title:Views of general practitioners on the role of CA125 in primary care to
diagnose ovarian cancer
Version: 2Date:24 April 2012
Reviewer: Marcia Hall
Reviewer's report:
My comments are below. I should disclose that I was a participant on the NICE
group that recommended that GPs have access to CA125 as part of their tools to
identify women with ovary cancer.
1. Is the question posed original, important and well defined?
The question is important although not exactly original. However given the very
recent adoption of the NICE guidance in the UK, and so no previous work has
been published on this in this country other than the papers quoted. The
endpoints are certainly not clear and this is really a descriptive piece of work
based on a very small response to a survey.
2 Are the data sound and well-controlled?
Not really applicable to this submission – yes as far as they are presented
3 Is the interpretation (discussion and conclusion) well balanced and supported
by the data?
Although the limitation of poor response to the survey (8%) has been mentioned
– it should be mentioned again within the body of the discussion and conclusion
text. Eg within the first para as this states that GPs are well aware of the typical
symptoms... well the 8% that answered are aware.
The data is clearly presented, such that it is, but great emphasis is placed on the
referral into secondary care of women with raised CA125 but no US evidence of
ovary cancer. Although seemingly contrary to the NICE guidance it would be
more helpful to explore why this is so rather than state it factually – simply
because women can have ovary cancer with normal imaging.
However, mention is made of the acceptance that women with ovary cancer can
have a normal CA125, confirming the general opinion that both US and CA125
are both important parts of a difficult jigsaw. It would make more sense to point
out that this survey of well informed and self-selected participants confirms this
fact!
It would be interesting to mention in the discussion if NICE had NOT
recommended that GPs have access to CA125 would there be any impact? –
questions on this would have been helpful too – eg reassure patients whose
CA125 is normal and reassure GP too! Fewer GPs involved on NICE group
agreed but in fact GP don’t see it very often....and the 6 secondary care doctors
were – radiologist, 2 x gyn onc surgeon, 2 x med onc and 1 x cancer unit
gynaecologist. The scope for development of these guidelines was very broad –
ranging from the diagnostic issues discussed here but also including whether
lymph node dissection should be done – what radiology was appropriate, was
histology always required and what chemotherapy was needed – hence the
inclusion of all the secondary care doctors.
It would be sensible to discuss the limitations that the NICE process has in
forming guidelines – it HAS to be (apparently) didactic and direct (NO ambiguity
allowed). Health economics are also an integral part of the NICE process. These
are the two reasons why the algorithm states CA125 first (cheaper than US for
everyone) and will not allow both investigations at once (although practically it is
very likely that this is what will happen).
Finally although mention is made of the aim of these guidelines in expediting the
diagnosis of such patients in order to improve treatment outcomes, the
discussion also needs to reiterate the latest theory that many of these serous
cancers probably arise from the fallopian tube and are thus ‘advanced’ (stage
II/III) from the start whenever this happens to have been discovered. Expediting
confirmation of this will therefore only reassure the patient that there is indeed
‘something wrong’ but is most unlikely to alter outcomes until our therapy has
improved. Explaining these unpleasant facts is often the most important and
helpful way for a GP to ease some of the anxiety induced by waiting for results.
4. Are the methods appropriate and well described and are sufficient details
given to evaluate and / or replicate work?
Yes methods well described although of limited application given very poor
response. Pity that the same survey couldn’t have been given to a captive
audience say at GP seminars on cancer and perhaps on another unrelated topic
(in order to reduce self-selection issue). I think the addition of such replica
surveys, although of smaller numbers might strengthen your case. Somewhat
surprised that GPs do not recognise endometriosis as likely precursor to
malignancy.
5. What are the strengths and weaknesses of the methods?
There was a distinct lack of any questions about bowel habit. This is a major
symptom of ovary cancer – many patients will be labelled as having irritable
bowel syndrome because of their frequent complaints of alternating diarrhoea
and constipation. Patients rarely offer up these symptoms, particularly if
something else is troubling them but very often the co-existence of bowel
problems significantly raises your concern about ovary cancer. This is a very
common feature of patients with serous ca ovary and these patients often get
referred to the gastroenterologists and then onto oncology. Also important to
remind GPs that IBS is part of ‘normal’ spectrum – just that these people’s
bowels reflect stress more readily than the average. Additional questions such as
what do GP’s think abdominal bloating is ? can it be “normal” (YES)
See above answer. Case histories are so borderline there wasn’t really any
correct answer for either scenario – so I am not sure exactly what they were
designed to show except that any pathway could have been correct for these
patients. Would be more helpful to have given ‘correct’ answers – so more likely
to refer 2WW if post menop but probably no real necessity for urgent referral and
review of bloating and repeat CA125 more sensible in younger age group. Again
– no information on bowel habit which GP should have asked about if bloating
main symptom.
6. Can the writing, organisation , tables and figures be improved?
What revisions are requested.
Cannot really draw conclusions from survey as it stands – not only very few GPs
answering but also no bowel symptoms included in any of the survey. I cannot
recommend this for publication but if the survey were repeated and perhaps
validated as discussed above it might then be a more helpful addition to the
literature
Are there any ethical or competing interests issues you would like to raise
No ethical / competing issues