Radiation Matches Heat in First Head-to-Head Trial for Colorectal Liver Metastases

For decades, patients whose colorectal cancer has spread to the liver in limited numbers have faced a frustrating gap in evidence: two widely used curative-intent treatments, microwave ablation and stereotactic body radiotherapy, had never been compared directly in a randomised trial. That gap has now been closed. The LAVA-CRLM trial, conducted at Copenhagen University Hospital Rigshospitalet and Herlev Hospital in Denmark, is the first prospective randomised phase II study to pit these two technologies against each other in patients with oligometastatic colorectal liver metastases. Its central finding is strikingly simple: when it comes to keeping treated tumours under control, the two modalities performed similarly. Where they diverged was in safety, with radiotherapy causing far fewer severe treatment-related side effects than the heat-based procedure.

The context matters enormously. Colorectal cancer is one of the most common malignancies worldwide, and the liver is its most frequent destination for metastatic spread. Roughly a quarter to a third of patients already have distant metastases at diagnosis, and another half or more will develop them during the course of their illness. For a carefully defined subgroup, those with so-called oligometastatic disease, typically fewer than five tumours in no more than two organs, aggressive local treatment with curative intent can produce prolonged disease control and even long-term survival. Surgical resection remains the gold standard, delivering local control rates above 90 percent and five-year survival between 35 and 60 percent. But not every patient is a surgical candidate, and for those who are not, the field has lacked rigorous comparative data to guide the choice between thermal ablation and ablative radiation.

Microwave ablation, or MWA, works by inserting a needle-like probe directly into the tumour, usually under general anaesthesia and real-time ultrasound guidance. Electromagnetic waves at microwave frequencies agitate water molecules within the tissue, generating frictional heat that coagulates and destroys the tumour along with a margin of surrounding liver. Operators in the trial tailored power delivery between 40 and 100 watts over sessions lasting four to fifteen minutes, and performed track ablation as the probe was withdrawn to reduce the risk of needle-track seeding. The technique is well established, supported by robust evidence for durable local control, and is generally preferred over other thermal methods when technically feasible. Yet it remains an invasive procedure, carrying the procedural risks of anaesthesia, probe placement, and in some cases laparoscopic or open surgical access.

Stereotactic body radiotherapy, or SBRT, takes an entirely different route to the same goal. Instead of physically entering the body, it delivers very high doses of precisely sculpted radiation in a handful of fractions, exploiting steep dose gradients to destroy the tumour while sparing healthy tissue. In LAVA-CRLM, the preferred regimen was 45 Gy delivered in three fractions over one week, prescribed so that the gross tumour received a biologically effective dose exceeding 173 Gy, well above thresholds previously associated with high local control rates. Most patients in the radiotherapy arm were treated on an integrated magnetic resonance imaging linear accelerator, an MR-linac, which allows clinicians to visualise soft tissue in real time and adapt the treatment plan daily as anatomy shifts. The remaining patients received conventional linac treatment with cone-beam CT guidance and fiducial tracking. Either way, the entire process is non-invasive and requires no general anaesthesia.

Between January 2019 and December 2024, the Danish team enrolled 100 patients with one to three liver metastases smaller than 4.0 centimetres, each judged suitable for both treatments by a hepatopancreatobiliary multidisciplinary team. Participants were randomly assigned in equal numbers to MWA or SBRT. After exclusions for screening failures, disease progression, or protocol deviations, the modified intention-to-treat population comprised 92 patients, 47 treated with microwave ablation and 45 with radiotherapy. The trial’s primary endpoint was freedom from local progression, meaning the treated lesion itself remained controlled, assessed after at least one year of follow-up by a radiologist blinded to which treatment each patient had received. New lesions elsewhere were tracked separately and did not count as local failures.

The results on local control were essentially a statistical tie. With a median follow-up of roughly three and a half years, local progression occurred in 33 percent of the SBRT group and 36 percent of the MWA group. Estimated one-year freedom from local progression was 83.0 percent with radiotherapy and 77.7 percent with ablation, a difference the investigators described as showing no evidence of a separation between groups, with a hazard ratio of 0.87 and a confidence interval spanning well below and above unity. Per-protocol analyses, restricted to patients who received their assigned treatment exactly as planned, told the same story. Overall survival likewise showed no meaningful difference: three-year survival was estimated at 71.5 percent after SBRT and 63.3 percent after MWA. The trial was explicitly not powered to prove equivalence, so the wide confidence intervals leave room for clinically relevant differences, but the point estimates are remarkably close for two technologies that could hardly be more different in execution.

Safety told a sharper story. During treatment and the first month afterwards, any-grade toxicity affected 38 percent of radiotherapy patients compared with 71 percent of ablation patients. More importantly, grade 2 or higher treatment-related toxicity occurred in just 3 percent of the SBRT group versus 25 percent of the MWA group, and all grade 3 or higher treatment-related events, affecting 8 percent of ablation patients, occurred in the MWA arm. The trial also recorded one treatment-related death: a 74-year-old patient developed hepatic necrosis with capsular perforation two days after percutaneous microwave ablation and died on the day of emergency surgery. Liver pain was by far the most common complaint in the ablation group, affecting 69 percent of patients during treatment, while fatigue dominated in the radiotherapy group. The investigators attribute the more favourable safety profile of SBRT to its non-invasive delivery, which avoids the procedural risks inherent in probe placement and anaesthesia, though they caution the trial was not formally powered for toxicity comparisons.

Quality of life, measured with the EORTC QLQ-C30 questionnaire on 441 completed assessments from 98 percent of participants, showed no difference between the groups over time. The authors suggest this may reflect the dominant influence of disease progression and systemic chemotherapy on long-term wellbeing, which can drown out differences attributable to the local treatment itself. They also note a subtlety in the biology: KRAS-mutated tumours, which some evidence links to poorer local control after radiation, were numerically more frequent in the ablation group, and the trial lacked systematic molecular profiling, a limitation when interpreting the local control estimates. Tumour genetics, including KRAS and TP53 alterations, is an emerging frontier in personalising the choice between ablation and radiation for liver metastases.

The implications for clinical practice are considerable. For patients with oligometastatic colorectal liver metastases of 3 centimetres or smaller, the trial supports considering SBRT alongside MWA in multidisciplinary treatment planning, with the safety data giving radiation a potential edge for lesions where both options are technically feasible. The ability to deliver SBRT fully non-invasively, particularly with MR-guided adaptive technology that tracks tumour motion and adjusts the plan daily, may expand options for patients who cannot tolerate anaesthesia or whose lesions sit near radiosensitive structures. At the same time, ablation retains advantages of its own, including shorter overall treatment time and a single-session approach that some patients prefer over the repeated hospital visits and breath-hold manoeuvres that MR-guided radiotherapy can entail. Individualised selection based on tumour location, size, patient fitness, and institutional expertise remains essential.

The Danish investigators are careful about the limits of their evidence. This was a phase II study in a single national network, designed to detect large differences rather than establish equivalence, and all treated metastases were 3.0 centimetres or smaller despite eligibility extending to 4.0 centimetres. Larger confirmatory trials are needed, and the ongoing COLLISION-XL study is expected to address the question for intermediate-sized lesions between 3 and 5 centimetres. Still, the trial marks a genuine milestone: the first randomised evidence that a beam of precisely focused radiation can match a probe burning tumours from the inside, while sending dramatically fewer patients to hospital with severe complications. For a patient population in which every treatment decision carries curative stakes, that is a finding worth paying attention to.

Subject of Research: A randomised phase II trial comparing microwave ablation and stereotactic body radiotherapy for oligometastatic colorectal liver metastases

Article Title: Microwave ablation versus stereotactic body radiotherapy for oligometastatic colorectal liver metastases (LAVA-CRLM): a prospective, randomised, phase II trial

Article References: Risumlund, S. L., Stick, L. B., Appelt, A., Vogelius, I. R., Nyhuus, B., Schultz, N. A., Penninga, L., van Overeem Felter, M., Josipovic, M., & Larsen, P. N. (2026). Microwave ablation versus stereotactic body radiotherapy for oligometastatic colorectal liver metastases (LAVA-CRLM): a prospective, randomised, phase II trial. The Lancet Regional Health – Europe, 71, Article 101879. https://doi.org/10.1016/j.lanepe.2026.101879

Image Credits: AI Generated

DOI: 10.1016/j.lanepe.2026.101879

Keywords: colorectal cancer, liver metastases, microwave ablation, stereotactic body radiotherapy, oligometastatic disease, randomised trial, local control, treatment toxicity, MR-linac, interventional oncology, radiation oncology, phase II trial