Ablation margins: what we know now and what lies ahead

Ablative therapies are becoming increasingly widespread and are now supported by a very robust and growing body of evidence, describes Marco Calandri (Turin, Italy), who discusses the consolidated role of ablative margins and challenges that must be addressed to drive progression.

The year 2025 marked a major milestone, with the well-known COLLISION trial demonstrating the non-inferiority of thermal ablation compared with surgery in selected colorectal liver metastases (CRLM) patients.¹ As ablation—driven primarily by high-volume referral centres— continues to consolidate its role, particularly in the hepatic setting, the need to homogenise and standardise outcomes has become increasingly compelling.

A provocative but necessary question therefore arises: do we really want to position ablation as a standard of care while accepting local tumour progression (LTP) rates that still vary substantially across centres? If the answer is no, how can these results be improved—and what role do ablative margins play in this process?

Four things we already know about ablative margins:

1. Ablative margins matter

There is now strong and consistent evidence that ablative margins are one of the most important determinants of local tumour control. From the early work to more recent studies, adequate margins have repeatedly been associated with lower recurrence rates, both in primary liver tumours and in metastatic disease.^2–4 At this point, the impact of ablative margins is no longer controversial.

2. Measuring ablative margins is difficult

While the concept of an ablative margin may appear straightforward, its assessment in clinical practice is complex. Thermal distortion of the liver parenchyma, differences between pre-and post-ablation anatomy including respiratory motion, and the need to identify the true minimal margin across all imaging planes all contribute to this challenge. Importantly, studies have demonstrated that visual inspection systematically overestimates the effective minimal ablative margin and can no longer be considered a reliable approach.⁵

3. Ablation confirmation software provides a strategic solution

Over the last few years, ablation confirmation software has emerged as an increasingly robust answer to these limitations. Available data consistently show that software-based margin assessment is superior to visual evaluation alone, that deformable image registration outperforms rigid registration, and that these tools perform best when intraprocedural computed tomography (CT) imaging is available, both before and after ablation. Notably, 2025 also saw the publication of the first randomised phase two trial in this field, the COVER-ALL trial, further strengthening the clinical relevance of ablation confirmation.⁶

4. A0, A1, and A2: Toward a shared standard

Ablation confirmation software also allows ablative margins to be defined in close parallel with surgical resection margins.⁷ In this framework, margins greater than 5mm are classified as A0, margins between 0–5mm as A1, and margins below 0mm as A2. This classification provides a common language that aligns ablation outcomes with surgical concepts and represents a concrete step toward greater standardisation and comparability across centres.

Three challenges we still need to address:

Looking ahead, several challenges remain. Among the many open issues in this field, three appear particularly urgent.

1. Software-related uncertainty must be understood

It is essential to acknowledge that the concept of the ablative margin inherently includes the margin of error of the ablation confirmation software itself. We are just at the beginning of the quantitative evaluation of this uncertainty.⁸ Further dedicated studies addressing software-related variability are therefore needed in order to understand the real value and the impact on margins’ thresholds.

2. Benchmarking across platforms is still missing.

Few comparative studies between different ablation confirmation platforms are available and more evidence is urgently required. This will be crucial to define shared benchmarks, and establish objective performance standards. Without this step, widespread adoption risks being driven more by availability than by evidence-based approach.

3. Workflow integration needs to continue evolving.

The integration of ablation confirmation systems at the end of all ablation workflows must continue to advance, regardless of the imaging modality used for lesion targeting, whether ultrasound, CT, or CT hepatic arteriography (CTHA). Moreover, given that many interventional radiologists perform ablations in angiography suites, wider implementation on cone-beam CT will be essential to ensure that ablation confirmation tools are accessible beyond specialised CT-based environments.⁹

The path forward is now clear, and the available evidence is both strong and compelling.¹⁰ However, only through rigorous validation, shared benchmarks, and continued implementation will ablative margin assessment establish itself as a cornerstone of high-quality ablation in 2026 and beyond.

References:

1. van der Lei, S., Puijk, R.S., Dijkstra, M., et al. (2025) ‘Thermal ablation versus surgical resection of small-size colorectal liver metastases (COLLISION): an international, randomised, controlled, phase 3 non-inferiority trial’, The Lancet Oncology, 26, pp. 187–199. https://doi.org/10.1016/S1470-2045(24)00660-0
2. Wang, X., Sofocleous, C.T., Erinjeri, J.P., et al. (2013) ‘Margin size is an independent predictor of local tumor progression after ablation of colon cancer liver metastases’, Cardiovascular and Interventional Radiology, 36, pp. 166–175. https://doi.org/10.1007/ s00270-012-0377-1
3. Shady, W., Petre, E.N., Gonen, M., et al. (2016) ‘Percutaneous radiofrequency ablation of colorectal cancer liver metastases: factors affecting outcomes—A 10-year experience at a single center’, Radiology, 278, pp. 601–611. https://doi.org/10.1148/ radiol.2015142489
4. De Cobelli, F., Calandri, M., Della Corte, A., et al. (2022) ‘Multi-institutional analysis of outcomes for thermosphere microwave ablation treatment of colorectal liver metastases: the SMAC study’, European Radiology, 32, pp. 4147–4159. https://doi. org/10.1007/s00330-021-08497-2
5. Laimer, G., Schullian, P., Putzer, D., et al. (2020) ‘Can accurate evaluation of the treatment success after radiofrequency ablation of liver tumors be achieved by visual inspection alone? Results of a blinded assessment with 38 interventional oncologists’, International Journal of Hyperthermia, 37, pp. 1362–1367. https://doi.org/10.1080/02656736.2020 .1857445
6. Odisio, B.C., Albuquerque, J., Lin, Y.-M., et al. (2025) ‘Software-based versus visual assessment of the minimal ablative margin in patients with liver tumours undergoing percutaneous thermal ablation (COVER-ALL): a randomised phase 2 trial’, The Lancet Gastroenterology & Hepatology, 10, pp. 442–451. https://doi.org/10.1016/S2468-1253(25)00024-X
7. Paolucci, I., Albuquerque Marques Silva, J., Lin, Y.-M., et al. (2024) ‘Identification of A0 minimum ablative margins for colorectal liver metastases: multicentre, retrospective study using deformable CT registration and artificial intelligence-based autosegmentation’, British Journal of Surgery, 111, znae165. https://doi. org/10.1093/bjs/znae165
8. Paolucci, I., Albuquerque, J., Siddiqi, N.S., et al. (2026) ‘The effects of measurement errors on minimum ablative margins after thermal ablation of liver tumors: a simulation study’, CVIR Oncology, 2, p. 1. https:// doi.org/10.1007/s44343-025-00029-9
9. Solbiati, M., Passera, K.M., Goldberg, S.N., et al. (2018) ‘A novel CT to cone-beam CT registration method enables immediate real-time intraprocedural three-dimensional assessment of ablative treatments of liver malignancies’, Cardiovascular and Interventional Radiology, 41, pp. 1049–1057. https:// doi.org/10.1007/s00270-018-1909-0
10. Paolucci, I., Albuquerque Marques Silva, J., Lin, Y.-M., et al. (2025) ‘Quantitative ablation confirmation methods in percutaneous thermal ablation of malignant liver tumors: technical insights, clinical evidence, and future outlook’, Radiology: Imaging Cancer, 7, e240293. https://doi.org/10.1148/ rycan.240293

Marco Calandri is an interventional radiologist at the University of Torino, Turin, Italy.