Question asked by: 
Attendee at Being Together Plymouth
Date asked: 
Oct 2015

Some women say their CA125s weren’t particularly raised prior to diagnosis. Could they be better followed up with CT PET scans, HE4 or the use of other algorithms?

Could PET scans, HE4 or other algorithms be used as markers of recurrence?
There are three parameters that you look for to pick up relapse. Symptoms and clinical examination, CA-125 and imaging.
Response by Guest experts from Being Together Plymouth

The question really is how do you pick up relapse and what do you do with it? There are three parameters that you look for to pick up relapse. One is the patient’s symptoms and clinical examination. Second, the CA125. Third, imaging of some description. You have to put all three into the melting pot. The patient’s symptoms are obviously very important. There are people who have disease, are totally asymptomatic and it’s low volume disease, doing no harm, and you can watch them for some time before you need to treat them. On the other hand, there are patients who complain of symptoms before the scan changes, and you have to listen. 

The scan is important but the frequency of doing scans will vary, and it will also vary on each individual patient as to whether you have an ultrasound or CT scan. Every so often, particularly in high risk patients, they need a scan to check things are okay. PET CT scan can be done from time to time. It’s not absolute and should not replace a standard CT scan. It gives a lot of radiation, but there are times when an ordinary CT scan does not pick up the cancer, the patient has symptoms and CA125 is rising, and a PET scan can be very useful in that situation. Unfortunately, it can also be negative. So it is not an absolute test. The third is the level of the CA125. CA125 can rise before the patient has any symptoms and before the scan becomes abnormal. You do not necessarily need to treat rising CA125, but it’s a warning shot to say, ‘Keep an eye out of things.’

There was a trial that came out of Mount Vernon Hospital in London that showed that treating just on CA125 without any CT evidence of disease or clinical symptoms does not necessarily give a benefit. However, I do feel that that trial has been overinterpreted in some places to say, ‘Stop doing CA125.’ 

I come back to where I started, I think that in the recognition of relapse, the three key things are the patient’s symptoms and signs, imaging and the CA125. You put everything into the melting pot to make an appropriate judgement on how best to treat that lady. 

HE4 (Human epididymis protein 4) is a different protein associated with ovarian cancers.  In the States it’s licensed to use for detection.  It’s not licensed here.  We have been involved in a trial with HE4 and it seems its main role is really to differentiate between women who have benign disease at the onset and who have cancer, and who should operate on them and what extent of surgery they should have.  It does seem to perform better in that setting.  In terms of follow up, if CA-125 is difficult to interpret and we know it is a good marker for a lot of women, then it’s difficult to believe that HE4 is going to be better in terms of when to have chemotherapy and when to start if it recurs.  The message about HE4 and follow up is that it’s not likely to be better than CA-125, is the way I would look at it.

I think a lot of what we learn about things is what we pick up in the media. It’s terrible when you’re a patient, because it’s almost every day there is something.  Hopefully my colleagues will say that if there’s something that really is obvious then we’ll be using it in the NHS. We have to, because there’s limited funds, but they’re not that limited if there is an obvious thing that we should use.