Written by: Madelon Dijkstra, M.D., PhD
Recently published in The Lancet Oncology, the randomised, international, multicentre, phase III non-inferiority COLLISION trial demonstrated comparable results between thermal ablation and surgical resection for small-size colorectal liver metastases, initiating re-evaluation of clinical practice and the previously held assumption that ablation should be reserved for unresectable lesions only. Speaking to Interventional News, principal investigator Martijn Meijerink (Amsterdam UMC, Amsterdam, The Netherlands) recognised “completely unexpected” results in their data concerning local control and tumour progression, with the potential to push the needle toward minimally invasive intervention in a broader range of lesions.
Between August 2017 and February 2024, 300 patients were randomly assigned to two groups—148 to the experimental treatment and 148 to the control treatment. Four patients in total were excluded as they were found to have other disease pathology. The trial met predefined halting criteria for early benefit, and it was deemed unethical to continue. It was determined that thermal ablation resulted in fewer side effects (28 cases [18.9%] vs. 67 cases [45.9%]) and shorter hospital stays. Serious side effects occurred in 11 patients (7.4%) in the ablation group and 29 patients (19.9%) in the surgery group—these included bleeding that needed intervention (one patient [1%] vs. eight patients [5.5%]) and infections requiring treatment (six patients [4%] vs. 11 patients [7.5%]). In the researchers’ analysis, local control was found to be superior following ablation—an “unanticipated” result, said Meijerink— with only a single patient in this group for whom local control was not achieved.
When asked if these results were close to his predictions, Meijerink commented that he expected overall survival to be identical. “What was completely unexpected was local control and tumour progression,” he said. “This outcome means that in small-size tumours, the vast majority can be locally controlled with ablation. Even if you had a perfect surgeon, it would still be unacceptable to continue resecting small-size tumours. We should focus on what I think is the next standard of care— ablation—because in high-volume, dedicated centres you can locally control tumours with this technique.”
The path Meijerink and colleagues at Amsterdam UMC took to arrive at this conclusion was one built from “trust”, he described, and was forged from over a decade’s worth of observation showing improved outcomes via thermal ablation. “We saw the majority of tumours weren’t coming back and our surgeons were completely open to a potential future where resection for smaller tumours is no longer the first option, then we started to make this principle concrete,” Meijerink stated.
Admittedly, he added that this collaborative relationship between interventional radiologists and surgeons at his institution is “unique” and that they are “lucky” to operate in this way. Although, Meijerink stated that part of the reason for initiating the COLLISION trial was to seek an “end to the discussions” between their departments on the best course of treatment.
The COLLISION trial included patients from 14 centres in The Netherlands, Belgium and Italy, with ten or fewer small-size (≤3cm) colorectal liver metastases, no extrahepatic metastases, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, stratified per centre, and according to their disease burden, into low, intermediate, and high disease burden subgroups.
Meijerink reflected that the process of setting up the trial was lengthy. Having finalised the study protocol in 2015, the search for funding “took a long time”, he said, but believes this extension was “a good thing”.
“We would have had a negative trial because we weren’t as good back then. We would have had more recurrences when compared to surgical resection, whereas now, we are much better at completely eradicating the disease. Even though it was frustrating, it’s good we have the results now and not ten years ago,” Meijerink explained.
In part, Meijerink added that technological advancements such as confirmation software are a central reason for the positive results of the COLLISION trial. “It’s a no-brainer. Eyeballing the tumour is not good enough—sitting down to check the margins and bring the needle back for any residual tumour while the patient is still under anaesthesia dramatically improved our results,” he said.
Despite advancements in devices and targeting software, Meijerink highlighted that inclusion criteria for the COLLISION trial stipulated institutions have ample experience with thermal ablation and must have performed more than 100 cases to meet this description. Although he believes their data are convincing, he cautioned less experienced centres from changing their practice too quickly, without first achieving recurrence rates below 10% in patients with small-size tumours.
“My suggestion for centres that want to change their practice—and I agree that we should all strive to—is to first look at your last 50 or 100 cases and see if your recurrence rates are below 10%. If they are not, I wouldn’t change anything for now. We cannot generalise the results without first making sure you’re doing a good job,” he stated.
To address the “steep learning curve” institutions can be met with when looking to implement change, Meijerink offered the COLLSION-2 trial, a stepped-wedge cluster trial comparing current practices to best practices. From confirmation software to antibiotic use and general anaesthesia, Meijerink et al—via a consensus panel meeting—will seek to define best practice and subsequently randomise centres.
“If your centre is enrolled in the trial, you will receive a call disclosing details of ‘best practice’ in regard to thermal ablation and will be given six weeks to implement it. These trials are very often positive because, not only do you improve your outcomes, but it’s a way for centres to achieve outcomes equal to the best performing centres,” Meijerink described.
“There’s a lot to improve and why should we do that? I think we, as interventional radiologists who are stepping into oncology should realise that we need to be highly dedicated. The patient is on the table to have their cancer eradicated—it’s not inflating a balloon and maybe it comes back and needs to be reinflated. We have to do a better job. It’s in human nature to say, ‘I think I got it, and if I didn’t, I’ll do it again in six months’, but that’s not our future. Our future is making sure you treated that patient the best way possible and to standardise this care among centres,” said Meijerink.
Meijerink and colleagues’ research efforts to solidify thermal ablation as the new standard of care are ongoing; the COLLISION XL trial, a randomised controlled trial comparing thermal ablation to stereotactic body radiotherapy (SBRT) for larger-size and unresectable colorectal liver metastases 3–5cm, is currently recruiting. “Thermal ablation more often fails to provide local control in larger tumours, but has shown equal recurrence rates to SBRT,” explained Meijerink. Their team is also recruiting for the COLLISION RELAPSE trial, comparing upfront repeat local treatment with thermal ablation and/or surgical resection versus neoadjuvant chemotherapy followed by local treatment for patients with new colorectal liver metastases in the first year after the initial local treatment.
Through these trials, Meijerink hopes to provide data that will place tumours up to 5cm within the remit of interventionalists who can provide minimally invasive, efficacious treatment. “Technological advancements are not stopping. In the future I’m sure we will be able to compete with surgery for patients with larger tumours,” Meijerink stated.