On June 2, 2024, Prof. Martijn Meijerink was presenting the final results of COLLISION trial at the American Society of Clinical Oncology meeting in Chicago. The multicentric randomized controlled trial aimed to compare thermal ablation with surgical resection for the treatment of small-size (≤3cm) resectable colorectal liver metastases. The results indicate that thermal ablation is an effective treatment option with similar overall and progression-free survival rates, reduced mortality, morbidity, and length of hospital stay compared to surgical resection. This will have a significant impact on future liver cancer care. In light of these findings, we have decided to put the trial and its results, and other significant aspects of the study in context of the history and future of percutaneous thermal ablation.
Fiat thermica - let there be heat!
The fundamental technique of thermal ablation dates back to 1891, when D’Arsonval demonstrated that RF waves could increase tissue temperature. The introduction of the Bovie knife in 1928 allowed tissue to be cauterized or cut by varying the RF current. However, it wasn't until 1990 that two independent researchers advanced the concept further. By replacing the Bovie knife with needles insulated to the tip, they enabled coagulation necrosis to be applied via a percutaneous tract (read history of ablation).
In contrast, the first documented successful liver resection was performed by German surgeon Carl Johann August Langenbuch in 1888 (read article). The journey to modern liver surgery began in the late 1950s with the introduction of advanced imaging tools. The integration of laparoscopy, robotics, alongside refinement of resection techniques has then further enhanced the safety and precision of liver surgeries. (read evolution of hepatic surgery)
Ablation, however, had significant ground to cover in bridging the decades-long gap in evidence generation and development compared to surgical resection.
The road towards modern ablation
Over the past 15 years, percutaneous ablation has advanced beyond initial methods like ethanol injection and early radiofrequency ablation. Innovations in imaging and ablation modalities as well as increasing clinical evidence have led to greater acceptance in international treatment guidelines. With the adoption of decision-support and guidance systems, physicians can effectively treat an increasing number of patients in a standardized manner (read meta-analysis).
The evidence is mounting that ablation is a viable competitor to surgical resection. It was therefore essential to conduct a comprehensive and objective comparison between the two treatments.
The Amsterdam Colorectal Liver Met Registry (AmCORE) compared repeat ablation versus repeat resection for recurrent colorectal liver metastases. Results showed no difference in survival, recurrence rates, or complications, but repeat thermal ablation had a shorter hospital stay. These findings were supported by the multicenter prospective cohort trial (MAVERRIC), which concluded that “Stereotactic ablation is a viable curative-intent treatment alternative to surgical resection for small resectable colorectal liver metastases”. The study showed similar 3-year overall survival rates, reinforcing the potential of ablation as an effective treatment option.
The stage was set for the next act to provide definitive answers on surgery versus thermal ablation: on June 2, 2024, the eagerly awaited results of the phase III COLLISION trial, were presented by Prof. Martijn Meijerink.
What is the COLLISION trial?
The COLLISION trial is a multi-center phase III single-blind prospective randomized controlled trial comparing efficacy of surgery versus thermal ablation. The main goal was to explore whether thermal ablation is non-inferior to surgical resection for patients with small-size (≤3 cm) resectable CRLM in terms of overall survival (read trial protocol).
While this trial does not produce entirely new results, its design is truly impressive and significantly distinguishes itself from previous studies. It is a prospective, single-blinded, randomized, and controlled study that was designed to enrolled over 600 patients across 15 centers in three countries. This protocol meets the relevant criteria for evidence Level 1B within the evidence-based medicine pyramid (the highest level below a systematic review of RCTs). Implementing such a protocol in clinical practice requires significant effort.
What are the results?
The results indicate that thermal ablation offers comparable local control and overall survival rates to those observed with surgical resection, while being associated with a superior safety profile, shorter hospital stay, and lower costs.
Overall Survival (OS): No significant difference (Hazard Ratio 1.042; 95% CI, 0.689-1.576; p = 0.846).
Local Control: Significantly better in the thermal ablation group (HR 0.184; 95% CI, 0.040-0.838; p = 0.029).
Progression-Free Survival (PFS): No significant differences for local (HR 0.833; 95% CI, 0.473-1.469; p = 0.528) and distant PFS (HR 0.982; 95% CI, 0.739-1.303; p = 0.898).
Procedure-related Mortality: Significantly lower in the thermal ablation group (0%) compared to the surgical resection group (2.1%).
Adverse Events: Significantly lower in the thermal ablation group (19%) compared to the surgical resection group (56%).
Length of Hospital Stay: Shorter for the thermal ablation group (median 1 day) compared to the surgical resection group (median 4 days).
Further information can be found in the ASCO abstract.
Why was the trial stopped early?
According to the initial protocol, a total of 687 patients should be enrolled to achieve sufficient statistical power for the analysis of the main outcome measures. Continuous interim analyses have revealed results that led the defined stopping rules to kick in and the trial being halted after enrollment of 341 patients. Most prominently, the conditional probability of >90% to prove the hypothesis of non-inferiority in Overall Survival was achieved. This can be interpreted as a testament to the strength of the presented results.
What does the community say?
Shortly after the presentation, several renowned representatives of interventional and surgical societies commented on the results:
Dr. Robert Lewandowski (President of Society of Interventional Radiology, read article): “This is tremendous news for patients around the world […] We hope the full data are published soon so we can operationalize this treatment in the field, move the standard of care forward and give patients new hope for not just treatment but recovery.
Dr. Åsmund Fretland (HPB surgeon at Oslo University, Norway, read statement): “Collision trial at ASCO showing non-inferiority for thermal ablation both for local recurrence and OS! A major step for minimally invasive treatments!”
Prof. Dr. Thiery Chapelle (HPB surgeon at UZA Antwerp, Belgium, read article): “We are pleased that the value of percutaneous thermal ablation is now internationally recognized. Hopefully, the positive results will be a lever to make ablation more and more the standard of care.”
Why where the results presented at the ASCO meeting?
On a rather speculative note, Prof. Meijerink has been quite thoughtful in presenting the results at the conference of the American Society of Clinical Oncology. As opposed to presenting at Interventional Oncology, or Interventional Radiology events, where the audience are already firm believers of ablation, the ASCO is a group largely of referring physicians (Medical Oncologists), who might have more power to decide on referral pathways, and impact treatment guidelines.
Whats next?
Recent studies have provided substantial evidence in support of percutaneous thermal ablation as the standard-of-care for the local treatment of patients with small-size colorectal liver metastases. Ablation shows comparable oncologic outcomes, with minimized morbidity and mortality rates, as well as decreased hospital stay. The partnership between leading European-African medical associations recently emphasized the crucial role of interventional oncology, particularly ablation. This collaboration is shifting the terminology from “resectable disease” to the more inclusive and empowering “locally treatable disease” (read more on it here).
Widespread use of decision-support and guidance systems enable standardized treatments within and across multiple centers. This improves the comparability of results from multicenter studies. Even with these excellent results, CAS-One IR has been shown in many studies to provide even better results, such as, to reduce LTP down to 5-8%1-2, and fewer complications / lower severity of complications3. A full list of CAS-One IR publications can be found here.
Despite the additional costs of using such systems, a recent study revealed a decrease in healthcare related costs of $ 38’000 (median costs from liver MDT conference 2 years onward) when a patient with liver metastasis is treated with stereotactic microwave ablation (using the CAS-One IR System) compared to surgical resection (read study). This evidence should also be of interest for economic decision makers at the hospital and healthcare system level.
One crucial aspect is the incorporation of software into the ablation confirmation process. There are a number of ongoing studies exploring this topic. As we await the results of trials such as NEW-COMET, COVER-ALL, and ACCLAIM, it's clear that the landscape of liver cancer treatment is evolving. We extend our appreciation to all those involved for their contributions to this critical research. With these advancements and the growing role of ablation, the future of liver cancer treatment looks bright—and hot.