Liver and Bile

Lancet Oncol. 2025;26(2):187-199

van der Lei S, Puijk RS, Dijkstra M, Schulz HH, Vos DJW, De Vries JJJ, Scheffer HJ, Lissenberg-Witte BI, Aldrighetti L, Arntz M, Barentsz MW, Besselink MG, Bracke B, Bruijnen RCG, Buffart TE, Burgmans MC, Chapelle T, Coolsen MME, de Boer SW, de Cobelli F, de Jong K, de Wilt JHW, Diederik AL, Dooper AMC, Draaisma WA, Eker HH, Erdmann JI, Futterer JJ, Geboers B, Groot GMC, Hagendoorn J, Hartgrink HH, Horsthuis K, Hurks R, Jenniskens SFM, Kater M, Kazemier G, Kist JW, Klaase JM, Knapen RRMM, Kruimer JWH, Lamers ABGN, Leclercq WKG, Liefers GJ, Manusama ER, Meier MAJ, Melenhorst MCAM, Mieog JSD, Molenaar QI, Nielsen K, Nijkamp MW, Nieuwenhuijs VB, Nota IMGC, Op de Beeck B, Overduin CG, Patijn GA, Potters FH, Ratti F, Rietema FJ, Ruiter SJS, Schouten EAC, Schreurs WH, Serafino G, Sietses C, Slooter GD, Smits MLJ, Soykan EA, Spaargaren GJ, Stommel MWJ, Timmer FEF, van Baardewijk LJ, van Dam RM, van Delden OM, van den Bemd BAT, van den Bergh JE, van den Boezem PB, van der Leij C, van der Meer RW, van der Meijs BBM, van der Ploeg APT, van der Reijden JJ, van Duijvendijk P, van Erkel AR, van Geel AM, van Heek NT, van Manen CJ, van Rijswijk CSP, van Waesberghe JHTM, Versteeg KS, Vink T, Zijlstra IAJ, Zonderhuis BM, Swijnenburg RJ, van den Tol MP, Meijerink MR

Thermal ablation versus surgical resection of small-size colorectal liver metastases (COLLISION): An international, randomised, controlled, phase 3 non-inferiority trial

Background: For patients with small-size colorectal liver metastases, growing evidence suggests thermal ablation to be associated with fewer adverse events and faster recovery than resection while also challenging resection in terms of local control and overall survival. This study assessed the potential non-inferiority of thermal ablation compared with surgical resection in patients with small-size resectable colorectal liver metastases.
Methods: Adult patients (aged ≥ 18 years) from 14 centres in the Netherlands, Belgium, and Italy with 10 or fewer small-size (≤ 3 cm) colorectal liver metastases, no extrahepatic metastases, and an Eastern Cooperative Oncology Group performance status of 0–2, were stratified per centre, and according to their disease burden, into low, intermediate, and high disease burden subgroups and randomly assigned 1:1 to receive either thermal ablation (experimental group) or surgical resection (control group) of all target colorectal liver metastases using the web-based module Castor electronic data capture with variable block sizes of 4, 6, and 8. Although at the operator’s discretion, a minimally invasive approach in both treatment groups was recommended. The primary endpoint was overall survival, assessed in the intention-to-treat population. A hazard ratio (HR) of 1.30 was considered the upper limit of non-inferiority for the primary endpoint. A preplanned interim analysis with predefined stopping rules for futility (conditional power to prove the null hypothesis < 20%) and early benefit (conditional power > 90%, superior safety outcomes for the experimental group, and no difference or superiority regarding local control for the experimental group) was done 12 months after enrolment of 50% of the planned sample size. Safety was assessed per treatment group.
Findings: Between August 7, 2017, and February 14, 2024, 300 patients were randomly assigned to the experimental group (n = 148, 100 male [68%] and 48 female [32%]; median age 67.9 years [interquartile range {IQR}, 29.2–85.7]) or to the control group (n = 148, 107 male [72%] and 41 female [28%]; median age 65.1 [IQR, 31.4–87.4]); 4 patients (2 in each treatment group) were excluded after randomisation because they were found to have other disease pathology. Median follow-up at the prespecified interim analysis was 28.9 months (IQR, 0.3–77.8). The trial was stopped early for meeting the predefined stopping rules: (1) a conditional likelihood to prove non-inferiority for overall survival of 90.5% (median overall survival not reached in both groups; hazard ratio [HR] = 1.05; 95% confidence interval [CI]: 0.69–1.58; p = 0.83), (2) a non-inferior local control (median local control not reached in both groups; HR = 0.13, 95% CI: 0.02–1.06; p = 0.057), and (3) a superior safety profile for the experimental group. Patients in the experimental group had fewer adverse events than those in the control group (28 [19%] vs. 67 [46%]; p < 0.0001). Serious adverse events occurred in 11 (7%) of 148 patients in the experimental group and 29 (20%) of 146 in the control group, mostly periprocedural haemorrhage requiring intervention (1 [1%] vs. 8 [5%]), and infectious complications requiring intervention (6 [4%] vs. 11 [8%]). There were no treatment-related deaths in the experimental group and 3 treatment-related deaths (2%) in the control group (2 due to postoperative cardiac complications and 1 due to sepsis and liver failure).

Interpretation: The assumption that thermal ablation should be reserved for unresectable colorectal liver metastases requires re-evaluation and the preferred treatment should be individualised and based on clinical characteristics and available expertise.

DOI:  10.1016/s1470-2045(24)00660-0