Thermal ablation versus surgical resection of small-size colorectal liver metastases (COLLISION): an international, randomised, controlled, phase 3 non-inferiority trial - 21/01/25

Doi : 10.1016/S1470-2045(24)00660-0

Susan van der Lei, MD ^a,^e,^v,^{*
Joint first authors}, Robbert S Puijk, MD PhD ^a,^e,^f,^{*
Joint first authors}, Madelon Dijkstra, MD PhD ^a,^e, Hannah H Schulz, MD ^a,^e, Danielle J W Vos, MD ^a,^e, Jan J J De Vries, MD ^f, Hester J Scheffer, MD PhD ^g, Birgit I Lissenberg-Witte, PhD ^b, Luca Aldrighetti, ProfMD ⁱ, Mark Arntz, MD ^k, Maarten W Barentsz, MD PhD ^m, Marc G Besselink, ProfMD ^c,^e, Bart Bracke, MD ^o, Rutger C G Bruijnen, MD ^q, Tineke E Buffart, MD PhD ^d,^e, Mark C Burgmans, MD PhD ^s, Thierry Chapelle, ProfMD ^o, Marielle M E Coolsen, MD PhD ^u, Sanne W de Boer, MD PhD ^v, Francesco de Cobelli, MD ^j, Koert de Jong, MD PhD ^w, Johannes H W de Wilt, ProfMD ^l, Arjen L Diederik, MD ^y, Anniek M C Dooper, MD ^c, Werner A Draaisma, MD ^z, Hasan H Eker, ProfMD ^aa, Joris I Erdmann, MD PhD ^c,^e, Jurgen J Futterer, ProfMD ^k, Bart Geboers, MD PhD ^a,^e,^ab, Gerie M C Groot, MD ^ac, Jeroen Hagendoorn, MD PhD ^r, Henk H Hartgrink, MD PhD ^t, Karin Horsthuis, MD PhD ^a, Rob Hurks, MD PhD ^a, Sjoerd F M Jenniskens, MD ^k, Matthijs Kater, MD ^x, Geert Kazemier, ProfMD ^c,^e, Jakob W Kist, MD PhD ^a, Joost M Klaase, ProfMD ^w, Robrecht R M M Knapen, MD ^v, Johan W H Kruimer, MD ^ae, Armand B G N Lamers, MD ^a, Wouter K G Leclercq, MD PhD ⁿ, Gerrit-Jan Liefers, MD PhD ^t, Eric R Manusama, MD PhD ^af, Mark A J Meier, MD ^ah, Marleen C A M Melenhorst, MD ^aj, J Sven D Mieog, MD PhD ^t, Quintus I Molenaar, ProfMD ^r, Karin Nielsen, MD PhD ^r,^ak, Maarten W Nijkamp, MD PhD ^w, Vincent B Nieuwenhuijs, MD PhD ^ai, Irene M G C Nota, MD ^a, Bart Op de Beeck, MD ^p, Christiaan G Overduin, PhD ^k, Gijs A Patijn, MD PhD ^ai, Fons H Potters, MD ^ah, Francesca Ratti, MD ⁱ, Floris J Rietema, MD ^g, Simeon J S Ruiter, PhD ^w, Evelien A C Schouten, MSc ^al, Wilhelmina H Schreurs, MD PhD ^h, Gianpiero Serafino, MD ^y, Colin Sietses, MD PhD ^ad, Gerrit D Slooter, MD PhD ⁿ, Maarten L J Smits, MD PhD ^q, Ezgi A Soykan, MD ^a, Gert-Jan Spaargaren, MD ^ac, Martijn W J Stommel, MD PhD ^l, Florentine E F Timmer, MD ^a,^e, Laurens J van Baardewijk, MD PhD ^m, Ronald M van Dam, MD PhD ^u, Otto M van Delden, ProfMD ^a, Bente A T van den Bemd, MD ^a, Janneke E van den Bergh, MD ^a, Peter B van den Boezem, MD PhD ^l, Christiaan van der Leij, MD PhD ^v, Rutger W van der Meer, MD PhD ^s, Bram B M van der Meijs, MD ^a, Augustinus P T van der Ploeg, MD PhD ⁿ, Jeroen J van der Reijden, MD ^m, Peter van Duijvendijk, MD PhD ^am, Arian R van Erkel, MD PhD ^s, Anne M van Geel, MD ^g, N Tjarda Van Heek, MD PhD ^ad, Christiaan J van Manen, MD ^ac, Carla S P van Rijswijk, MD PhD ^s, Jan Hein T M van Waesberghe, MD PhD ^a, Kathelijn S Versteeg, MD PhD ^d,^e, Ted Vink, MD ^ag, Ijsbrand A J Zijlstra, MD PhD ^a, Barbara M Zonderhuis, MD ^c,^e, Rutger-Jan Swijnenburg, MD PhD ^c,^e, M Petrousjka van den Tol, MD PhD ^af,^{^{†
Joint senior authors}}, Martijn R Meijerink, ProfMD ^a,^{^{†
Joint senior authors},}⁎

^a Department of Radiology and Nuclear Medicine, Amsterdam UMC location VUmc, Amsterdam, Netherlands

^b Department of Epidemiology and Data Science, Amsterdam UMC location VUmc, Amsterdam, Netherlands

^c Department of Surgery, Amsterdam UMC location VUmc, Amsterdam, Netherlands

^d Department of Medical Oncology, Amsterdam UMC location VUmc, Amsterdam, Netherlands

^e Cancer Centre Amsterdam, Treatment and Quality of Life, Amsterdam, Netherlands

^f Department of Radiology, OLVG Hospital, Amsterdam, Netherlands

^g Department of Radiology, Noordwest Hospital, Alkmaar, Netherlands

^h Department of Surgery, Noordwest Hospital, Alkmaar, Netherlands

ⁱ Department of Surgery, San Raffaele Hospital, Milan, Italy

^j Department of Radiology, San Raffaele Hospital, Milan, Italy

^k Department of Medical Imaging, Radiology, Radboud University Medical Centre, Nijmegen, Netherlands

^l Department of Surgery, Radboud University Medical Centre, Nijmegen, Netherlands

^m Department of Radiology, Maxima Medical Centre, Veldhoven, Netherlands

ⁿ Department of Surgery, Maxima Medical Centre, Veldhoven, Netherlands

^o Department of Surgery, University Hospital Antwerp, Antwerp, Belgium

^p Department of Radiology, University Hospital Antwerp, Antwerp, Belgium

^q Department of Radiology, UMC Utrecht, Utrecht, Netherlands

^r Department of Surgery, UMC Utrecht, Utrecht, Netherlands

^s Department of Radiology, Leiden University Medical Centre, Leiden, Netherlands

^t Department of Surgery, Leiden University Medical Centre, Leiden, Netherlands

^u Department of Surgery, Maastricht University Medical Centre, Maastricht, Netherlands

^v Department of Radiology, Maastricht University Medical Centre, Maastricht, Netherlands

^w Department of Surgery, University Medical Centre Groningen, Groningen, Netherlands

^x Department of Radiology, University Medical Centre Groningen, Groningen, Netherlands

^y Department of Radiology, Jeroen Bosch Ziekenhuis, ‘s-Hertogenbosch, Netherlands

^z Department of Surgery, Jeroen Bosch Ziekenhuis, ‘s-Hertogenbosch, Netherlands

^aa Department of Surgery, University Hospital Ghent, Ghent, Belgium

^ab Department of Radiology, Westmead Hospital, Westmead, Sydney, NSW, Australia

^ac Department of Radiology, Gelderse Vallei Hospital, Ede, Netherlands

^ad Department of Surgery, Gelderse Vallei Hospital, Ede, Netherlands

^ae Department of Radiology, Flevoziekenhuis, Almere, Netherlands

^af Department of Surgery, Medical Centre Leeuwarden, Leeuwarden, Netherlands

^ag Department of Radiology, Medical Centre Leeuwarden, Leeuwarden, Netherlands

^ah Department of Radiology, Isala Klinieken, Zwolle, Netherlands

^ai Department of Surgery, Isala Klinieken, Zwolle, Netherlands

^aj Department of Radiology, Hospital Amstelland, Amstelveen, Netherlands

^ak Department of Surgery, Erasmus MC, Rotterdam, Netherlands

^al Department of Scientific Administration, National Cancer Institute, Amsterdam, Netherlands

^am Department of Surgery, Gelre Hospital, Apeldoorn, Netherlands

^* Correspondence to: Prof Dr Martijn R Meijerink, Department of Radiology and Nuclear Medicine, Cancer Centre Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam 1081 HV, Netherlands Department of Radiology and Nuclear Medicine Cancer Centre Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam HV 1081 Netherlands

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Summary

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 ten 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. This trial is registered with ClinicalTrials.gov, NCT03088150.

Findings

Between Aug 7, 2017, and Feb 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 [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]); four patients (two 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; HR 1·05; 95% 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 (one [1%] vs eight [5%]), and infectious complications requiring intervention (six [4%] vs 11 [8%]). There were no treatment-related deaths in the experimental group and three treatment-related deaths (2%) in the control group (two due to postoperative cardiac complications and one 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.