Saturday, December 01, 2007

Cancer Scare Story

A headline in today's Times of London highlights Government plans to 'target' cancer treatment in the NHS. Stung by reports that cancer patients survive less well in the UK than elsewhere in Europe they are to concentrate resources on cancer care.

My first response is that someone is riding a hobby horse. I suspect it is the College of Radiologists who are trying to get the Government to buy more radiotherapy machines. Now that may well be a good thing, but it certainly lowers morale for cancer sufferers if they think that they are not getting the best that is available.

I strongly suspect that cancer statistics are inaccurate. I once asked a famous epidemiologist about this and he replied that he thought the figures about right as around 30% of people who are supposed to have cancer don't have it while around 30% of those who are supposed not to have cancer do have it. I hope he was joking.

A statistic that I often quote concerns prostate cancer which became ten times commoner in the USA during the 1990s as a result of the availability of the PSA test. The NHS restricted access to this test and as a result it became only two and a half times more common in the UK. There was much mockery traveling East across the Atlantic. Britain lags behind. Urologists in America became very busy. Cures multiplied but despite this the numbers of deaths from prostate cancer barely altered. Extra operations in the NHS bring no financial reward. We did not see a great burgeoning of prostate surgery, although more people had prostatic biopsies (a cynic might say that if you badger your doctor for a PSA you deserve to have a prostatic biopsy). In the UK the number of deaths from prostate cancer also stayed the same. In fact pro-rata it stayed the same as it was in America. What did become commoner in America was post-operative impotence and incontinence. But then this just produces more work for urologists.

Cancer statistics in the UK are obtained from death certificates and hospital admission diagnoses. They are bolstered by histopathology reports. Of course, not everybody with cancer gets admitted to hospital and even if they do the diagnosis may be wrong. Autopsies are getting more and more uncommon. They have to be done if the coroner orders it but he will only do so if the death is unexpected or foul play is suspected or if no medical attendant is willing to say that death was from natural causes. Again a cynic might say that the pathologist gets no extra financial reward for doing an autopsy but if the coroner orders one he gets a fee.

When I was a young doctor, we eagerly attended the mortuary every day to witness the post-mortem examinations. The pathologist had flair. Like a magician he would gradually lay out the salient facts and the offending organs until, like Poirot in the drawing room, he would reveal the dénouement. In the last year that I was at Bournemouth there were only eleven autopsies that were not ordered by the coroner. Diagnostic imaging has so improved that patients die without mystery. Physicians imagine that they have solved the puzzle. Yet I doubt this is so, and what is written on death certificates may seldom tell the whole truth.

Recently I saw a death certificate for a woman who died in her seventies. The cause of death was given as 1a Myocardial ischemia 1b Coronary artery thrombosis and coronary artery atherosclerosis. 2 Hodgkin’s disease – treated.

This gives the impression that this was a woman who was successfully treated for her Hodgkin’s disease who eventually succumbed to heart disease, and when you hear that she smoked for 50 years, you might justifiably call it a medical success. Here was a woman who developed a form of cancer that was treated by the doctors; but nobody lives for ever and if you abuse yourself with tobacco for 50 years then you’re bound to get hardening of the arteries.

Nothing could be further from the truth. In fact this was a woman with chronic lymphocytic leukemia whose disease progressed after a couple of years watch and wait and who was quite reasonably treated with fludarabine and cyclophosphamide. She had a complete remission though this was punctuated by chest infections. Two and a half years out she developed enlarging lymph nodes in her neck accompanied by night sweats, weight loss and fatigue, although her blood remained free of leukemia. CT scan showed that the lymph nodes were extending into her chest and fine needle aspirate showed small and medium sized lymphocytes ‘consistent with recurrence of her CLL’.

On this basis her doctor diagnosed recurrence of her CLL and treated her with Campath. She didn’t really get better so the doctor switched to CHOP. After deteriorating further she was referred to a tertiary referral center where they did what should have been done when she first relapsed – a lymph node biopsy. This showed Hodgkin’s disease and she was started on appropriate Hodgkin’s disease therapy. Unfortunately, she died midway through the first course, probably because she had become anemic, was transfused and then started on an anthracycline – all too much for her heart to bear. The coronary thrombosis was the terminal event, but the true cause of death was CLL – not treated, but mistreated.

Fine needle aspirate is a useless means of diagnosing lymph node enlargement. Even normal lymph nodes will show a mixture of small and medium lymphocytes. The clinical picture of enlarging lymph nodes with systemic symptoms and no blood relapse is characteristic of Richter’s syndrome, and we know that it is becoming commoner in patients who have been treated with fludarabine. Although in the past Richter’s syndrome has been a form of diffuse large B cell lymphoma, more recently it has taken the form of Hodgkin’s disease, possibly because of the release from T-cell control of the EB virus.

Campath is a good drug for treating fludarabine refractory CLL, but its strengths are in treating blood and bone marrow disease; it is poor at treating disease in lymph nodes.

There was no mention of CLL on the death certificate.

Is it ignorance? Is it laziness? Is it understaffing? Is it a systems failure? Probably a bit of all four. So when the headlines scream CANCER SCARE STORY there may be something in it, but almost certainly not what the article is about.


Vance Esler said...

Wow, Terry. You have touched on a number of subjects here upon which we could expand.

I was not aware that PSA's are not done as much in the UK as they are here in the US. However, in our area we have discussed the controversy over whether prostate screening has any beneficial effects. My suspicion has been that we diagnose lots of prostate cancer that would never have been clinically important. But without the crystal ball, how does one know? Accordingly, I let my doctor do the PSA test, but before I run off and have surgery or radiation, I'll think about it a bit.

It is also interesting to get your take on death certificates in the UK. The story you tell is also very much true here. How many physicians-in-training, do you suppose, have listed "cardiac arrest" or "respiratory arrest" as the cause of death, not thinking that of course the final common event in any death is that the heart and lungs stop moving -- yet that is a far cry from being the actual cause of death.

GIGO. Garbage in; garbage out. Many more stats than we care to admit probably fall into that category.

But it is all we have, and I guess we do the best we can with what we have...

Terry Hamblin said...

In today's Lancet Oncology Volume 8, Issue 12, Pages 1041-1148 (December 2007) the epidemiologists get to work on criticising cancer statistic comparisons between countries. In addition to the points I made about prostate cancer, they say that the same appliesto breast cancer and melanoma, where screening not only diagnoses patients early (thus extending the lead-time survival) but also picks up cases that would never be diagnosed clinically. In addition the Italian statistics only came from the affluent north and excluded figures from the poor south. The American figures on lung cancer only included biopsy proven cases. Of course it is the ones where biopsy is regarded as unwarranted because of extensive inoperabole disease that have the worst prognosis. The German statistics only surveyed 1% of the population - but which 1%? Was it representative?

As I suspected when making allowances for all these varaibles the differences between Western countries largely disappeared

Vance Esler said...

Yes, in some of the arguments that I have gotten into in the blogosphere, some have repeatedly talked about how the US has such poor stats compared to European countries.

So, I wondered, why do all the Europeans come over here to attend ASH and ASCO? And the more I listened to the abstracts presented over the years, the more I thought, too, that cancer care is pretty much the same all over (at least the heme/onc end of it).

In other words, when we follow the recommendations from Italian and British studies in breast cancer over here, why would our patients do so much worse? In fact, they do not. Nor do theirs do any worse than ours.

The similarities are greater than the differences, I think.

Anonymous said...

You wrote, "a cynic might say that if you badger your doctor for a PSA you deserve to have a prostatic biopsy"

That statement astounds me. No one with a heart would ever say or think that, unless that person had some solid hatred in their hearts.

Do you feel that way sometimes about the CLL patients you see? Do they bug you with requests for things you cannot or will not prescribe? Dying patients must sometimes be quite annoying.

Terry Hamblin said...

'a cynic might say that if you badger your doctor for a PSA you deserve to have a prostatic biopsy'

Have you ever had a prostatic biopsy? I have. This was a remark directed at myself. If I hadn't been so silly as to order myself a PSA I wouldn't have been put through the pain of the biopsy. A cynic might say, "Serves you right."

As for your other remarks, they are really out of order, but I assume that they are written out of ignorance and as they are unsigned I won't hold a grudge against all the anonymice out there.