Impact of time to ablation on survival outcomes in patients with colorectal liver metastases: an inverse probability-weighted cohort study

The optimal timing for thermal ablation (TA) in patients with colorectal liver metastases (CRLM) eligible for local curative therapy remains undefined. This study aimed to evaluate the impact of time to ablation (TTA) on long-term survival outcomes.

We retrospectively analyzed 220 patients with ablatable CRLM (≤ 5 liver metastases, maximum diameter ≤ 3 cm) who underwent TA between January 2015 and December 2022. Based on the TTA, patients were stratified into three groups: upfront TA (UTA, ≤ 3 months, n = 113), short-term delayed TA (DTA, 3-6 months, n = 59), and long‑term DTA (> 6 months, n = 48). Inverse probability of treatment weighting (IPTW) was applied to reduce baseline selection bias. The primary endpoint was progression‑free survival (PFS), and the secondary endpoint was overall survival (OS).

After IPTW adjustment, the difference in PFS among the three groups was statistically significant (P = 0.012). The 1‑, 3‑, and 5‑year PFS rates were 61.5%, 31.2%, and 30.2% in the UTA; 47.7%, 15.9%, and 4.7% in the short‑term DTA; and 53.4%, 8.5%, and 3.1% in the long‑term DTA. Multivariable Cox regression identified both short-term DTA and long‑term DTA as an independent risk factor for worse PFS (HR = 1.80. 95% CI: 1.20−2.70, PP = 0.005); and HR = 1.99, 95% CI: 1.20–3.31, P = 0.008). No significant difference in OS was observed among the three groups. Subgroup analyses showed that DTA was associated with poorer PFS than UTA in patients with CEA > 5 ng/mL, synchronous metastases, N1−2 stage, or lymphovascular invasion. Moreover, among patients receiving UTA, adding neoadjuvant chemotherapy did not provide additional PFS or OS benefit compared with ablation alone (P > 0.05).

In patients with ablatable CRLM, UTA significantly improves PFS compared with DTA, and DTA is an independent risk factor for worse PFS. Therefore, for eligible patients, UTA is recommended in preference to prolonged systemic therapy.