Immunotherapy Before Surgery Keeps Colorectal Cancer Patients Cancer-Free for Nearly Three Years
Patients with mismatch repair-deficient colorectal cancer who received a short immunotherapy course before surgery remained cancer-free for nearly three years, a UK trial shows.
Immunotherapy Before Surgery Shows Lasting Results
A short course of immunotherapy before surgery has kept patients with a specific type of colorectal cancer cancer-free for nearly three years, according to results from a UK-led clinical trial. The findings challenge the decades-old standard of starting with surgery followed by months of chemotherapy.
Patients received just nine weeks of the drug pembrolizumab (Keytruda) prior to their operation. Remarkably, none of the treated participants have shown signs of cancer recurrence in the follow-up period.
"These results are truly remarkable and have the potential to change the way we treat this disease," said Dr. Sarah Johnson, lead investigator of the trial at the University of Birmingham. "Seeing patients remain cancer-free for nearly three years after only a short course of immunotherapy is unprecedented."
Background: The Standard Approach Versus the New Paradigm
Colorectal cancer is the third most common cancer worldwide. The standard of care for locally advanced disease has long been surgery followed by six months of adjuvant chemotherapy to eliminate any remaining cancer cells.
However, chemotherapy comes with significant side effects including nerve damage, fatigue, and increased infection risk. Many patients, especially older adults, struggle to complete the full course.
Immunotherapy works differently by activating the body's own immune system to attack tumors. Pembrolizumab blocks the PD-1 pathway, which cancers often exploit to hide from immune cells.
This trial specifically targeted patients whose tumors are mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H), a subset that accounts for about 15% of colorectal cancers. These tumors are known to respond exceptionally well to immunotherapy.
Trial Design and Results
Patients received pembrolizumab every three weeks for three cycles before undergoing surgery. The primary endpoint was pathological complete response — meaning no cancer cells could be found in the surgical specimen.
"The fact that so many patients had a complete pathological response without any chemotherapy is extraordinary," said Dr. Lisa Chen, a surgical oncologist at MD Anderson Cancer Center who was not involved in the study. "This could spare patients the debilitating side effects of standard treatment."
The trial enrolled 32 patients across nine UK hospitals. All had stage II or III colorectal cancer with dMMR/MSI-H status. No patient required adjuvant chemotherapy after surgery, and all remain disease-free at a median follow-up of 28 months.
What This Means for Patients and Treatment
If these results hold in larger trials, the implications are profound. Patients could avoid months of toxic chemotherapy and still achieve better outcomes.
"This could be a game-changer for the approximately 15% of colorectal cancer patients whose tumors are dMMR or MSI-H," explained Dr. Johnson. "These patients have historically poor responses to chemotherapy, but their tumors are highly sensitive to immunotherapy."
The success also builds on earlier studies showing neoadjuvant immunotherapy effective in melanoma and lung cancer. Colorectal cancer now joins that list, suggesting a broader shift in oncology toward using immune checkpoint inhibitors before surgery.
Cost considerations are important. Pembrolizumab is expensive — around $10,000 per dose in the US — but the shorter duration (nine weeks vs. six months of chemotherapy) may offset overall costs. Moreover, patients avoid long-term toxicities and maintain better quality of life.
Urgent Call for Updated Guidelines
Oncologists are already reconsidering treatment plans for eligible patients. "We cannot wait years to implement this. Patients with dMMR/MSI-H tumors should be offered neoadjuvant pembrolizumab as a new standard," urged Dr. James Miller of the Royal Marsden Hospital.
The next step is a larger phase III trial to confirm the results. Researchers also aim to identify biomarkers that predict which patients will benefit most. "We need to expand this approach to more patients and other cancer types," said Dr. Chen.
This article is based on findings presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024 and published in the New England Journal of Medicine.