Current evidence for the treatment of liver metastases
Liver metastases from colorectal cancer (CRC) represent a major clinical challenge, as they are the leading cause of death in patients with metastatic disease. The standard of care for resectable liver metastases remains surgical resection, which has been shown to improve long-term survival, with 5-year overall survival (OS) rates ranging from 40% to 60% in selected patients(1).
Among non-surgical options, thermal ablation techniques such as radiofrequency ablation (RFA) and microwave ablation (MWA) have gained prominence. The recently published COLLISION trial compared surgical resection and RFA in patients with small (≤3 cm) liver metastases. RFA demonstrated non-inferior overall survival compared to surgery while offering reduced morbidity and shorter hospital stays(2).
However, a significant proportion of patients are not eligible for surgery or RFA/MWA due to comorbidity, poor performance status, or complex anatomical localizations.
SBRT in the treatment of colorectal liver metastases – Current data
SBRT has emerged as a promising ablative treatment for colorectal liver metastases, particularly in patients who are ineligible for surgery or RFA. Patient selection criteria for SBRT typically include:
- A limited number of liver metastases (commonly ≤5 lesions);
- Sufficient hepatic reserve (e.g., >700cc);
Although there are no phase III randomized clinical trials evaluating the use of SBRT in the management of colorectal liver metastases, several prospective studies have demonstrated promising results. A meta-analysis of eighteen studies including 656 patients with a reported pooled 1-year LC estimate of 67% ranging from 50 to 95% (3).
The wide range of reported outcomes is attributable to variations in treatment regimens. Studies with the highest local control rates use biologically effective doses (BED) >100 Gy, commonly delivered in 3-5 fractions (e.g., 45-60 Gy in 3 fractions or 50-60 Gy in 5 fractions)(3).
Findings from prospective trials are promising. A recently published phase II study involving 105 liver metastases, 72% of which originated from colorectal cancer, reported a 4-year local control rate of 78.4%, with a median progression-free survival (PFS) of 27.7 months(4). Patients with lesions measuring ≤5 cm demonstrated significantly improved median liver-PFS (p = 0.006) and overall survival (p = 0.018). Notably, no acute or late toxicities of grade ≥3 were observed.
Clinical indications, future trials, and immunotherapy synergy
Based on current evidence, SBRT is now considered a viable option for patients with colorectal liver metastases who are ineligible for resection or RFA. Key indications include:
- Oligometastatic disease (≤5 metastases) with controlled primary tumour
- Contraindication to surgery or percutaneous ablation
- Recurrent liver metastases after previous local therapy.
Ongoing randomized trials aim to refine the role of SBRT. The SABR-COMET-3 and SABR-COMET-10 trials are investigating SBRT versus standard systemic therapy in patients with oligometastatic CRC among other primaries, with preliminary data suggesting potential survival benefits(5).
Beyond local control, there is growing interest in the immunomodulatory effects of SBRT. Preclinical and clinical data indicate that SBRT may enhance the efficacy of immunotherapy by increasing tumour antigen presentation and immune infiltration(6). A recently published early-phase trial investigated the combination of the PD-L1 inhibitor atezolizumab with SBRT in advanced colorectal cancer patients, demonstrating feasibility, manageable toxicity, and potential immune-mediated effects while identifying biomarkers associated with treatment response(7).
SBRT is now a recognized option for treating colorectal liver metastases, demonstrating high local control rates and a favourable toxicity profile. Ongoing trials continue to refine its role alongside surgery and thermal ablation. Moreover, its potential synergy with immunotherapy presents new research opportunities. As more data emerge, SBRT is expected to play an increasingly vital role in the multimodal management of metastatic colorectal cancer.
