COMMENTARY

'Shattering': Why Even a Month's Cancer Delay Matters

Prof Karol Sikora

Disclosures

November 06, 2020

This transcript has been edited for clarity.

Hello, my name is Professor Karol Sikora. I'm an oncologist here in London. And what I'd like to do today is look at a paper that appeared yesterday in The British Medical Journal, looking at mortality due to cancer treatment delays. It's a meta-analysis. It's done by a group in Queen's University, Kingston, Ontario, also at the London School of Hygiene and Tropical Medicine (LSHTM), and King's College London.

I guess the main driver for this was Ajay Aggarwal, associate professor, LSHTM, who was once my registrar, and is a very bright chap. There's no doubt, he's done a good job with his colleagues at analysing a very complex matter.

Not an Emergency

We know that delay in cancer treatment is bad. What we don't know is how much delay is permissible.

It's clearly not an emergency. It's not like a myocardial infarction, where you're going to stent within hours, if you're going to get the maximum effect to spare the troubled myocardium. With cancer, we assume that we can wait probably a month, maybe 2 months before we rush into treatment.

And that's how all over the world diagnostic and staging systems are based: that there is no hurry.

What this paper does, very interestingly, it goes through the world literature - and I'll come back to that in a moment - and looks at the consequence of a 4 week delay.

Now to me, 4 weeks is neither here nor there, and I wouldn't be too worried. But indeed, what this paper shows is, we should worry about just a 4 week delay. It's very apposite that it's come at the time of COVID-19, when 4 weeks delay in cancer services all over the world has become extremely common, just because the system's broken down mainly at the diagnostic end.

Also, patients are delaying coming forward, because primary care isn't necessarily able to cope with them.

Meta-analysis

So let's look at what happened. They took publications between 2000 and 2020, a 20 year span. And they collected them all up, and then analysed them. And, indeed, they collected a huge number of publications, something like 2843. They whittled that down to 275. And then when they looked at the robustness of the data, how effective it was, they took that further down to just 34 papers.

And what they looked for is a whole range of cancers, they looked at seven cancers, and the cancers they looked at were bladder, breast, colon, including rectum, lung, cervix, and head and neck cancer.

And what they were looking for in these 34 studies is an association between delay in starting treatment and mortality at a later stage. So this is a pretty exclusive thing to be looking for.

The delay could be in surgery, and that was common during the height of the pandemic in April, when all cancer services in the UK, were still working, but getting into the system was difficult, it was difficult to get the diagnostic pathway open.

And then they also looked at chemotherapy, systemic therapy delays, and radiotherapy delays.

Now the quality of the data because it wasn't collected specifically to look at the consequences on mortality of a 4 week delay, is very variable. And that's the weakness of the study. And there's nothing you can do about it. The strength of a meta-analysis is you get lots of numbers, 1.2 million patients are in this study.

The weakness of it, of course, is that it's not designed in advance to answer the very question we want, which in this case is what are the consequences of a 4 week delay?

'Shattering'

Well, let's go to the findings. They looked at the increased risk of death for nearly all these indications. And it turned out to be 6% to 8% increase if there's a 4-week delay.

Now that's pretty shattering, because it means that our current services where we say well, let's just have a 62 day target, a 31 day target and so on, that's way beyond the 4 weeks.

So we're operating in a system that we've inherited, really, that says there is no urgency in cancer treatment.

So the other thing they found if there was a surgical delay of 12 weeks in breast cancer, you've got a much bigger risk of mortality, and that it would go up, to up to 26% if there was a 12 week delay.

This tallies very well with the data published in The Lancet in July of this year, from a group in London that looked at month-by-month delays and how much it would impact on overall survival.

The difference between the two studies is that this study is a meta-analysis of existing literature, The Lancet paper was basically a very sophisticated back-of-the-envelope calculation of what happened if you increase the delay month-on-month from 1 month to 6 months across a range of cancers.

The problem is, different cancers grow at different rates. Different cancers have different routes of spread, and different levels of aggression. And so, for an individual patient, it's not possible to make the prediction of what the delay would cause.

I thought that the paper was good; it was the best you could do with the data. And the conclusion is a 4-week delay in treatment is associated with increase in mortality across all common forms of cancer treatment, with longer delays being increasingly detrimental, which seems a fair conclusion.

Why didn't they pick prostate cancer? It was excluded because, of course, it's a very different situation, where most people are not delayed. They're actually put on hormone therapy. And so there is no delay there for treatment. Once they reach an oncologist or a urologist, they're put straight onto hormone therapy.

Also, the nature of prostate cancer is very different. It tends to be slow growing, indolent, going on for many years, even in patients with metastatic cancer. So it's not a good cancer to look at.

But there was remarkable consistency across the 34 papers that showed that 4 weeks is bad news for cancer patients.

Why Is the UK Slower?

What does this mean? You know, one thing that I've lived with for the last 30 years is the fact that Britain is poorer in it's survival data across the board for cancer, but not quite across the board, not for leukaemias, germ cell tumours, paediatric cancers, and complex cancers. But for the common cancers.

It can't be the quality of care, once you've got cancer, that's making a difference. There are no magic drugs that're causing a change in survival. The pharma industry might like to say, well, Britain doesn't spend enough on chemotherapy, and that's why its results are poorer, but that's not the real reason.

The real reason has to be delay in the early stages; delay in getting started on treatment. We know that in Britain, the 1 year survival rate is significantly lower than the rest of Europe, more so than the 5 year or the 10 year survival rate.

That tells you that a lot of patients are presenting late, they're presenting with high stage cancers, whereas our colleagues in Europe are seeing lower stage cancers. And that would explain the difference.

So the problem here is diagnostics. It's not actually getting to treatment. Once you know you've got cancer, once you've got the histology report from a biopsy, and you've got the imaging report from the MRI, or PET CT, or CT or whatever, you're in business, you go to cancer treatment. And there's usually not much delay in that.

The delays come in getting to the phase where you've got a packet of diagnostics all worked up, MDT [multi-disciplinary team] decided on treatment, and you move forward.

And that's what we've got to work on. In France, Germany, in Italy, even with COVID-19 you can get a CT within a week. Here, unless you know you've got cancer, unless you phone up, it's much slower to get that.

So moving forward. I think this is an interesting study. We'll see more of it. We need to look at the number of life years lost. We've got all sorts of things to ask about this.

Will it change the way cancer services are run? I hope so. I think it's not an emergency. We don't have to treat cancer the same day it's diagnosed, but we have to really smarten up the upfront diagnostic pathways, and I think we'll see some of that going on over the next year or 2 once we get over the COVID-19 problems.

This is Karol Sikora, I'd love to hear from you what you think. Thank you.

You can follow Prof Sikora on Twitter.

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