Concept image of a cancer cell. Image credits: Pachon in Motion/Pexels.
For decades, the standard of care for bowel cancer has been a grueling, predictable cycle: surgery first, then months of chemotherapy to mop up any leftover cancerous cells. We hope it doesn’t come back. But far too often, it does. In fact, in many cases, the cancer returns within a few years, even after everything appears to have gone right.
However, a small clinical trial reports a way that could end this loop.
Instead of reaching for the scalpel first, doctors used immunotherapy to prime the body’s defences, basically teaching the body how to detect and fight tumors. Nearly three years later, the results are stunning: not a single patient in the trial has seen their cancer return. For a disease that ranks as the second leading cause of cancer deaths globally, this is a game changer.
Not an entirely new idea
The trial, NEOPRISM-CRC (Neoadjuvant Pembrolizumab in stratified medicine – Colorectal), was led by researchers at University College London. It focused on patients with stage two or stage three bowel cancer (also called colorectal cancer) who carry a specific genetic signature known as MMR-deficient or MSI-high.
These tumors are packed with mutations, which makes them easier for the immune system to recognize once it is properly activated. This subtype accounts for only about 10–15% of such bowel cancers, which possibly means this a targeted rather than universal approach.
The activation came from pembrolizumab, an immunotherapy drug designed to remove the natural inhibitory signals that cancer places on immune cells to make them inactive.
While this type of treatment has already shown promise in advanced cancers, using it before surgery in earlier-stage disease is still a relatively new idea.
There have been hints, though, that this strategy could work. For example, a previous study in rectal cancer showed that immunotherapy alone could make tumors disappear in some patients without the need for surgery.
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However, those results left a key question unanswered: would such dramatic responses actually last over time?
What happens when immunotherapy comes first
In this trial, researchers treated 32 patients with three doses of pembrolizumab over nine weeks before surgery, instead of following the usual path of surgery first and chemotherapy afterward.
In this approach, patients did not require the standard post-operative chemotherapy. Early signs were encouraging, with more than half of the patients showing no detectable cancer after treatment and surgery.
For example, one patient in the trial, a 73-year-old diagnosed with stage three bowel cancer, recovered after just a few doses of immunotherapy, according to his doctors. More than three years later, he remains cancer-free.
“The outcome of the surgery was essentially that the cancer had melted away, these were the doctor’s words. The immunotherapy had had an almost immediate effect,” the patient said.
However, what makes this study stand out is what happened next. After 33 months of follow-up, no patients have experienced a relapse so far. Even in cases where small traces of cancer remained after surgery, the disease did not grow or spread.
To understand why, the team went beyond standard monitoring. They developed personalized blood tests capable of detecting tiny fragments of tumor DNA circulating in the bloodstream. When this DNA disappeared, it was a strong signal that the cancer had been cleared at a deeper level.
They also analyzed tumor samples to study immune activity before treatment began, identifying patterns that may help predict who will respond best. Compared to standard care, where about a quarter of similar patients typically see their cancer return within three years, the difference is almost unbelievable.
“Seeing that no patients have experienced a cancer recurrence after almost three years of follow-up is extremely encouraging and strengthens our confidence that pembrolizumab is a safe and highly effective treatment to improve outcomes in patients with high-risk bowel cancers,” Kai-Keen Shiu, one of the doctors involved in the trial and an oncologist at the University College London Hospital, said
A chemo-free cancer treatment
The idea of delaying surgery in favor of early immunotherapy challenges a long-standing medical instinct. If these findings hold up in larger studies, this could change how at least one subset of bowel cancers is treated.
It also raises the possibility that some patients could avoid chemotherapy altogether, sparing them months of side effects without compromising outcomes.
“What is particularly exciting is that we now may be able to predict who will respond to the treatment using personalised blood tests and immune profiling,” Shiu said.
“These tools could help us tailor our approach, identifying patients who are doing well and may need less therapy before and after surgery versus patients at higher risk of disease progression or relapse who need additional treatment,” he added.
The researchers now plan to expand the trial to include more patients and to explore whether similar strategies could work in other forms of cancer.
To know more about the trial, you can visit here.