Thermal Ablation Noninferior to Surgery in Small-Size Colorectal Liver Metastases

Treatment with thermal ablation was noninferior to surgical resection in small-size colorectal liver metastases, according to data from COLLISION, an international, randomized, controlled phase three non-inferiority trial published in The Lancet Oncology.

Following the randomization of 148 patients to the thermal ablation group and 148 to the surgical resection treatment group between Aug. 7, 2017, and Feb. 14, 2024, investigators stopped the trial early for meeting the predefined stopping rules at a median follow-up of 28.9 months. These conditions for stopping include: a conditional likelihood to prove non-inferiority for overall survival (OS) of 90.5%; a non-inferior local control; and a superior safety profile for the experimental group.

Investigators reported that the median OS not reached in both groups (hazard ratio [HR], 1.05), the median local control was not reached in both groups (HR, 0.13) and that patients in the experimental group had fewer side effects than those in the control group.

“The assumption that thermal ablation should be reserved for unresectable colorectal liver metastases requires re-evaluation and the preferred treatment should be individualized and based on clinical characteristics and available expertise,” lead study author, Dr. Susan van der Lei, and colleagues wrote in the journal article.

van der Lei currently works in the Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, at VU University Medical Center Amsterdam, in the Netherlands.

Although surgical resection remains the standard treatment approach for patients with colorectal liver metastases, over the past two decades, thermal ablation has gained traction as an alternative. Thermal ablation is given either alongside surgery or as a standalone option for patients with high surgical risk, extensive prior abdominal surgery or anatomically unresectable tumors. Furthermore, thermal ablation offers a parenchyma-sparing approach that effectively eradicates disease in select cases. 

However, the ease of repeating ablations for local tumor progression has sparked debate over whether thermal ablation may replace surgery for small, resectable metastases. Some treatment centers continue to use surgical resection, while others increasingly prioritize ablation for small tumors. Although earlier meta-analyses suggested thermal ablation was inferior to surgery, recent studies report comparable survival outcomes. Based on this knowledge gap, the phase 3 COLLISION trial aimed to evaluate the non-inferiority of thermal ablation versus surgical resection in patients with resectable colorectal liver metastases measuring 3 centimeters or smaller.

The Methods to The Investigation

The COLLISION trial was conducted by the Dutch Colorectal Cancer Group and recruited patients from 14 centers across the Netherlands, Belgium and Italy. Adult patients were eligible for trial enrollment so long as they presented with fewer than 10 resectable and ablatable colorectal liver metastases measuring 3 cm or less. Those with extrahepatic disease, an ECOG status of less than two or prior locoregional liver treatment were not eligible for trial enrollment. The study explains that patients, “were stratified per center, and according to their disease burden, into low, intermediate and high disease burden subgroups and randomly assigned [one-to-one].” Patients were then able to receive either thermal ablation in the experimental group or surgical resection in the control group of all target colorectal liver metastases.

Multidisciplinary tumor boards initially assessed eligibility before cases were reviewed by a centralized panel of experienced interventional radiologists and hepatobiliary surgeons. Notably, consensus on ablatability and resectability was required before randomization. Patients underwent standard pre-procedural evaluations, including imaging and lab work, before being registered in the trial database. Surgical resection approaches — open, laparoscopic or robot-assisted — were left to the discretion of the treating surgeons. Similarly, physicians determined the ablation device, needle guidance method and procedural approach. All ablation procedures followed manufacturer guidelines and adhered to predefined resectability and ablatability criteria, ensuring consistency in treatment application.

The primary end point of the study was OS. Safety; local tumor progression-free survival (PFS); distant tumor PFS; loss of local control, defined as the time elapsed from randomization until the first detection of locally recurrent disease that was not retreated with surgery or ablation; local control, defined as the percentage of patients in whom the target tumors were eventually eradicated; and length of hospital stay, were all secondary outcomes which were measured.

Delving Deeper into Additional Outcomes and Safety Data

“The trial demonstrated a high likelihood of proving non-inferiority regarding OS, non-inferior local control and fewer complications with thermal ablation compared with surgical resection for small-size colorectal liver metastasis,” investigators reported.

Looking to the results, the investigators reported no difference between the treatment groups concerning distant tumor PFS (9.6 months in the experimental group versus 8 4 months in the control group), as well as no significant differences in the comparison of local tumor PFS between the two study groups. However, there was a significant difference in the length of hospital stay between the two treatments, with a median duration of 1 day with the experimental group compared with 4 days in the control group.

Regarding safety, patients had fewer side effects in the experimental group compared with those in the control group (19% versus 46%). In the thermal ablation group, 7% of patients reported serious side effects compared with 20% in the surgical resection group. These side effects included mostly periprocedural hemorrhage requiring intervention, as well as infectious complications requiring intervention. Although there were no treatment-related deaths in the experimental group, there were three in the control group due to postoperative cardiac complications, sepsis and liver failure.

“Both thermal ablation and surgical resection should be considered effective treatment options for patients with colorectal liver metastases. The assumption that thermal ablation should only be used for unresectable colorectal liver metastases needs to be reconsidered and our results advocate a more individualized approach to treatment. Clinicians should consider offering both treatment options and tailor the choice to the individual patient’s needs.” van der Lei and colleagues concluded.

Reference:

"Thermal ablation versus surgical resection of small-size colorectal liver metastases (COLLISION): an international, randomized, controlled, phase 3 non-inferiority trial," by Dr. Susan van der Lei, et al. The Lancet Oncology.

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