Remove the lymph nodes immediately, or wait and see if the cancer will indeed return? With more early colon cancer patients, physicians will now choose to monitor them regularly, instead of operating on them. With a new nationwide study, coordinated by UMC Utrecht, researchers aim to confirm that this treatment approach is better for both the patient and healthcare as a whole.
When colon cancer is detected at an early stage, doctors can often remove the cancer with minimally invasive surgery during the colonoscopy. With some patients, additional surgery will be performed, to remove the lymph nodes. Physicians do so because cancer cells could also be located in the lymph nodes, allowing the disease to spread remotely, to the liver or lungs, for example.
That extra surgery is stressful, and recovery may take a long time. Also, serious complications and long-term symptoms could arise. All the more burdensome when one realizes that the surgery often turns out to have been unnecessary. In fact, with about 90 percent of patients, the pathologist eventually will find no cancer cells in the removed lymph nodes. In addition, there are strong indications that the risk of distant metastasis is hardly reduced by removing lymph nodes with tumor cells.
Low or high risk?
Leon Moons is a gastroenterologist at UMC Utrecht and project leader of the new, nationwide study CROSSROADS. For this study, UMC Utrecht is collaborating with at least 55 Dutch hospitals, the Dutch Federation of Medical Specialists (FMS) and the ZonMw program ZE&GG (Zorgevaluatie & Gepast Gebruik, or ‘Care Evaluation & Appropriate Use’ ).
“Normally, pathologists analyze the removed cancer and a decision is made based on a number of criteria whether additional surgery should be performed,” Leon explains. “In a portion of patients, about 30 percent, we do not need to operate, but in some people there is a risk of metastases to the lymph nodes.”
Patients with metastatic risk are classified as low- or high-risk. Only those with very low risk (less than 5 percent) are not operated on. They are monitored annually. In the high-risk group, lymph nodes are removed as a standard procedure. But that high-risk group is still huge: it could involve people who have a 6 percent or less chance of metastasis, but also those who have a 30 or 60 percent risk of metastasis, for example.
“That means that worldwide still a lot of people are unnecessarily burdened with that surgery. In the Netherlands, we are therefore a bit more progressive and have been trying to fine-tune that large high-risk group for years. When is ‘high risk’ really high? Does surgery always improve the chance of survival in that broad, diverse group? Based on that, we’ve identified a subgroup: the patients with a metastatic risk of 15 percent or less.”
In this subgroup, Leon says there are no gains to be made by removing lymph nodes at an early stage. “Several studies conclude this. In these patients, the risk of distant metastases will increase only 1 to 2 percent when we wait, actively monitor and only operate on them once we will actually see on a CT scan that the lymph nodes have changed. And that marginal increase is immediately outweighed by the risks associated with additional surgery at an earlier stage.”
For example, 1 to 2 percent of patients die as a result of that surgical procedure. “Furthermore, people end up in the ICU, have to recover for a long time, suffer from scarring, or have to miss a piece of a bowel. This will have a great impact on their chances of survival and quality of life. Especially a shame when you consider that in the vast majority of people the surgery would not have been necessary at all, because the lymph nodes turn out to be clean afterwards.”
“Surgery turns out to have been unnecessary with most people because it hardly affects the risk of metastasis.”
Patient gets to choose
Within the CROSSROADS study, doctors will no longer directly remove lymph nodes in patients with a metastatic risk of 15 percent or less at participating hospitals. These patients will be spared complex surgery, allowing them to return to their normal lives sooner. Instead, they will receive active follow-ups: their blood values will be checked every year, and they will get a colonoscopy and CT scan then.
ZonMw has granted 1.8 million euros to CROSSROADS within the ZE&GG program. UMC Utrecht coordinates the research project, in which 55 hospitals are now participating. In the very short term, Leon expects that all Dutch hospitals will join them.
But the research extends beyond just this subgroup. “Patients with a metastatic rate of 15 to 25 percent can now choose: would they like the additional surgery right away or do they prefer the active follow-up? Obviously, this choice is difficult for patients. Of course, their treating physicians will help them to choose. And within CROSSROADS, we are going to create videos and other educational material with the Dutch Colon Cancer Foundation (Stichting Darmkanker) to help patients choose the treatment that suits them best.”
Special approach
Normally, a scientific study is conducted first, and then it can take up to 15 years before a ‘national guideline’, or standard treatment, is updated. This works differently with CROSSROADS: the new treatment approach is immediately put into practice. Leon: “In fact, the national guideline has already been adapted and will start February 2025. This is possible because we have already learnt so much from previous research and practical experience.”
The special approach of this project stems from an initiative of the Dutch Federation of Medical Specialists, ZonMw and ZE&GG. “Usually scientific studies look at a ‘novelty,’ a new, promising treatment, for which a grant is given. But these three parties thought: shouldn’t we identify existing treatments that we could apply more appropriately?”
By reasoning this way, not only patients can be helped directly but also healthcare in general, as staff and equipment, for example, are deployed more efficiently and affordably.
Leon: “Gastroenterologists, together with colleagues from surgery, radiology and pathology, also came up with a number of ideas at the time, including that surgery for early colon cancer does not always have added value. And fortunately, we can now energetically pursue these ideas thanks to this grant. With CROSSROADS, we will be able to collect plenty of data to assess the impact of the new guideline.”
Healthcare costs lower
The researchers will monitor the patients’ five-year survival rates. The patients will also complete questionnaires that will closely monitor their quality of life. Do they suffer less from complications? Does the wait-and-see policy make them more fearful that the cancer will return?
Furthermore, the researchers are charting whether the new strategy has resulted in lower costs. One would suspect that is indeed the case because, after all, less surgeries will be performed. At the same time, however, healthcare personnel will have to perform more checkups. “But the costs of those extra follow-ups do not outweigh the expenses of surgery. Some 10,000 euros per patient will be saved by the new guideline, we suspect.”
The researchers need about two years to treat enough people according to the new guideline. Then, five years of annual follow-ups will follow. “After about seven years, we will have collected enough data and can evaluate the new national guideline. But in the meantime, thankfully, no people will have been operated on unnecessarily.”
Colon cancer screening helps
In the Netherlands, everyone aged between 55 and 75 years old receives a call to participate in the national bowel cancer screening:
If people would like to participate, they’ll receive a stool test through the mail.
Then, they’ll have to send some stool to Bevolkingsonderzoek Nederland, the organization that coordinates the Dutch national health screenings.
There, the stool will be examined: does it contain blood?
If no blood is found, people will receive another invitation after two years.
If blood is discovered in the stool, polyps or colon cancer may be present. Polyps (lumps in the bowel) are usually harmless but may also develop into cancer.
In case of blood, people will be invited for a colonoscopy (an internal visual examination of the colon).
Gastroenterologist Leon Moons: “Colon cancer hardly ever causes any symptoms at the beginning, so people are not likely to go to the doctor. Thanks to the national screening, people with bowel cancer are now detected more quickly.” This makes it all the more important for people to always participate in the screening.
Can I participate?
At any hospital participating in the CROSSROADS study, lymph nodes are not removed immediately in case of a metastatic risk of 15 percent or less. Risk of colon cancer spreading between 15 to 25 percent? Then, patients are automatically given the choice between surgery or the active follow-ups. So, you don’t have to apply specifically for this.
Because the new national guideline requires it, other Dutch hospitals will soon follow this new treatment strategy as well.
Not sure whether your hospital already works according to the new national guideline and/or participates in CROSSROADS? Consult with your GP or specialist.
