
Cancer is a complex and challenging disease to treat, but one of the most powerful tools for stopping it lies within us: our immune system.
This fact is particularly important in bowel cancer (colorectal cancer). Scientists have found that bowel tumours with larger numbers of immune cells in specific areas have a lower risk of returning after surgery. It’s as if these tumours are hemmed in by the body’s defences, so it’s harder for individual cancer cells to escape the surgeon’s knife.
Soon, doctors could have a new way of working with those defences, making the treatment decisions that come after surgery much easier. An expert team led by one of our researchers has shown that an AI test can analyse important CD3 immune cells in stage 2 bowel tumours and identify the people who most need chemotherapy as a secondary shield to stop their cancer coming back.
The study, which was published in the Journal of Clinical Oncology last year, was conducted by the National Pathology Imaging Co-operative (NPIC) through a grant from Innovate UK.
“This has the potential to be the most important test patients with early-stage bowel cancer ask for,” says Dr Christopher Williams, the lead researcher and a Cancer Research UK Clinical Trials Research Fellow at the University of Leeds’ School of Medicine.
Williams, who specialises in treating people with bowel cancer, is speaking from experience.
“It’s one of the most difficult conversations that we have in the clinic: should you or shouldn’t you have chemotherapy after your surgery,” he says. “And that conversation is most difficult in stage 2 bowel cancer, where your chances of benefit, we know, are lesser.”
Thanks to our QUASAR trial, which ran from the 1990s into the 2000s, we know that giving people with bowel cancer chemotherapy after surgery helps more of them stay cancer-free for longer.
But stage 2 bowel cancers are in a difficult grey area for doctors like Williams. They’re not as far advanced as (late stage) stage 3 bowel cancers, which have already shown clear signs of spreading, meaning there’s a higher chance some cancer cells might be left behind after surgery. On the other side, they’re not as localised as stage 1 bowel cancers, which haven’t grown into the deeper layers of the bowel and very rarely need adjuvant treatments.
So, when he’s talking to patients who’ve had their stage 2 bowel tumours surgically removed, Williams explains that they could be in one of three groups. Most of them will be in group one, which means they have no cancer cells left after surgery and so nothing to gain from further chemotherapy. The rest could be in group two, which means they’ll receive chemotherapy that will kill their remaining cancer cells, or group three, with some remaining cancer cells that chemotherapy won’t be able to get rid of.
Those groups seem clearly defined, but there’s still an underlying problem. “Today, I have no way of knowing which one of those three groups the patient will be in when I’m speaking to them, or when I’m delivering the chemotherapy,” says Williams.
All this means some people who receive chemotherapy after surgery for stage 2 bowel cancer will be putting their lives on hold and dealing with potentially difficult side effects for no reason at all. Because of the limitations of our current tools, we just don’t know who these people might be.
“That’s a really hard thing for an individual patient to absorb,” says Williams. “So, anything that helps us define the risk more precisely is really useful.”
The CD3 test that Williams has been studying, which was developed with Roche Diagnostics, does exactly that.
Using data from the QUASAR trial, Williams’ team has shown that the new AI-powered test can sort people into three groups based on their actual risk of cancer recurrence. It works by assessing and comparing the density of CD3 (and CD8) T cells in different parts of the tumour and generating a ‘CD3 Score’. The study found that those whose CD3 Score put them in the highest risk group had a three times higher risk of their cancer returning in the five years after surgery than those in the lowest risk group.