This study demonstrated that the use of laparoscopic CARe to treat CRLM yielded similar perioperative and oncological outcomes to those of laparoscopic resection alone after PSM. This is the first study to compare the safety and efficacy of these two types of surgery for multiple CRLM via PSM analysis.

Several previous studies have compared the perioperative outcomes of CARe with those of resection alone. Liu et al. [15] showed that CARe was associated with a reduced major hepatectomy rate (5.2% vs. 21.9%, P = 0.001), a lower incidence of postoperative hepatic insufficiency (0.0% vs. 5.2%, P = 0.023), and a shorter postoperative hospital stay (7 vs. 8 days, P = 0.019). de Graaff et al. [20] reported similar results, as they found that the incidence of liver failure after CARe was lower than that after resection alone (1.9% vs. 0.6%, P = 0.017). Xourafas et al. [19] reported that CARe could reduce postoperative morbidity (22% vs. 13%, P < 0.0001). Karanicolas et al. [21] found lower blood loss (300 vs. 500 mL, P < 0.01) and a shorter length of hospital stay (7 vs. 9 days, P < 0.01) in the CARe group. Although the results varied among these studies, it is clear that CARe offers advantages in terms of short-term surgical outcomes. However, the perioperative outcomes of laparoscopic CARe were not superior to those of laparoscopic resection in our study. Before PSM, the operative time significantly increased in the laparoscopic CARe group. After PSM, the operation time was still longer in the laparoscopic CARe group, but the difference was not significantly different. There may be two primary reasons for the longer operation time in the laparoscopic CARe group. First, a greater number of lesions requiring surgical intervention were present in the combined CARe group in this study. Additionally, laparoscopic ablation demands more specialized expertise, precise planning for ablation, and navigation of the learning curve associated with laparoscopic ablation techniques [28]. Collectively, despite a higher bilobar involvement rate and a greater number of lesions, laparoscopic CARe demonstrated no adverse impact on perioperative outcomes. These findings support its role as a safe and effective minimally invasive strategy for managing multiple CRLM.

Almost all previous studies reported no difference in long-term oncological outcomes between CARe and resection alone for patients with CRLM [15,16,17,18,19,20,21,22,23,24]. Similar results were found in our matched cohort, with comparable oncological outcomes between the laparoscopic CARe group and the laparoscopic resection group. However, the median RFS was shorter in the laparoscopic CARe group before PSM. The poorer RFS observed in the laparoscopic CARe group before PSM may be attributed to a larger number of CRLM and a higher proportion of bilobar distribution in these patients. The Cox proportional hazards regression model confirmed this possibility, with multivariate analysis revealing that the number of metastases was independently associated with RFS. This may be also attributed to the higher tumour burden leading to earlier recurrence in the laparoscopic CARe group, as well as suboptimal microscopic margin control associated with ablation. Although the number of metastases is no longer a limitation of surgery for CRLM, it remains a negative prognostic factor [36]. Masuda et al. [35] reported that for patients with < 4 lesions, the OS in the CARe group was worse than that in the resection group (5 year OS: 34.4% vs. 58.9%, P = 0.007). In contrast, for patients with ≥ 4 tumours, the OS was comparable between the two groups (5 year OS: 31.9% vs. 34.1%, P = 0.48). Furthermore, although the median RFS was shorter in the laparoscopic CARe group before PSM in our study, the two groups had similar recurrence patterns and OS. However, the median follow-up of 27.5 months, along with a considerable number of censored patients at early time points in the Kaplan-Meier curves, warrants cautious interpretation of the OS results.

Similar to previous reports, the most common recurrence site after hepatectomy was intrahepatic [17, 37]. The study by Imai et al. [17] showed no statistically significant difference in the recurrence site between the CARe group and the resection group, which aligns with our findings. Additionally, we found no significant differences in the timing or treatment of recurrence between the two groups. This may account for the lack of a significant difference in long-term survival between the two groups, despite the CARe group having more lesions, greater bilobar involvement, and a higher pre-matching recurrence rate. This observation is likely due to the availability of comparable and effective post-recurrence treatment options, which contributed to similar survival outcomes in both groups [34].

Laparoscopic CARe has been applied to the management of CRLM [25, 26], but few relevant studies exist. Serenari et al. [38] investigated the factors associated with textbook outcomes in liver surgery [39] following CARe for CRLM. Multivariate analysis revealed that the use of a minimally invasive approach was significantly associated with the achievement of optimal outcomes. Vandeputte et al. [26] reported that the minimally invasive approach led to improved perioperative outcomes. There are currently no studies comparing the outcomes between laparoscopic CARe and laparoscopic resection alone for CRLM. We believe that our findings support the efficacy and safety of laparoscopic CARe for CRLM from another perspective.

As mentioned previously, CARe is frequently employed in patients with high tumor burden. For these patients, numerous treatment options exist, including chemotherapy, molecular targeted therapy, immunotherapy, TACE, SBRT. However, this approach raises several potential concerns. First, it risks missing the ‘window of opportunity’ for surgery. Some patients experience early disease progression due to tumor resistance to chemotherapy, whereas others achieve a clinical complete response, which makes accurate delineation of surgical resection margins particularly challenging [40]. Second, chemotherapy-induced liver injury may increase the complexity of surgery and the risk of postoperative complications. For instance, oxaliplatin-associated sinusoidal injury has been shown to increase intraoperative blood loss and postoperative morbidity [41]. Moreover, studies have shown that oxaliplatin-related sinusoidal obstruction syndrome is also linked to earlier disease recurrence after radical surgery [42]. Recent evidence further suggests that perioperative chemotherapy does not confer additional survival benefits for patients with resectable CRLM, as demonstrated in both real-world data and randomized controlled trials (e.g., EORTC 40983 and JCOG0603) [43,44,45]. In line with this understanding, our institution’s multidisciplinary team prioritizes radical liver resection. Therefore, patients with CRLM considered suitable for surgical intervention, particularly those with resectable or borderline resectable disease, are prioritized for upfront surgery. Therefore, in our cohort, very few patients received preoperative treatments such as TACE, TARE, or SBRT, due to their potential to interfere with subsequent surgical procedures.

As previously reported, ablation has been shown to stimulate the tumor immune microenvironment and enhance the anti-tumor effects of immunotherapy [46]. Ablation elicits the release of tumor-associated antigens through physical destruction of tumor tissue. These released antigens are subsequently captured, processed, and presented to T cells, particularly CD8 + cytotoxic T lymphocytes, by antigen-presenting cells, thereby activating a specific anti-tumor immune response [47, 48]. Furthermore, thermal ablation also enhances the infiltration of anti-tumor immune cells, such as NK cells and CD8 + cytotoxic T lymphocytes [49, 50]. Immune checkpoint inhibitors (ICIs) function by blocking inhibitory signals within the immune system, thereby restoring the anti-tumor activity of T cells. Therefore, ablation may foster a favorable tumor microenvironment for immune cells, and its combination with ICIs would be particularly beneficial. The combination of ablation and ICIs has been demonstrated to enhance T cell-mediated anti-tumor immunity by promoting Th1 cell polarization, characterized by increased Th1 cytokine production and concomitant reduction of Th2 cytokines [51]. Consequently, we hypothesize that combining CARe with ICIs may represent a potential therapeutic strategy to improve outcomes in CRLM. Although the combination of ICIs and ablation exhibits synergistic anti-tumor effects in preclinical and clinical studies, robust clinical evidence supporting its efficacy remains limited. Future investigation into the combination of CARe and ICIs represents a notably interesting and important research avenue.

This study has several limitations. First, this study was a retrospective study with inevitable selection bias. Even with careful PSM analysis, selection bias may not have been completely avoided. Further prospective controlled studies with large sample sizes are needed to provide high-level clinical evidence. Second, the follow-up duration for survival in this study was relatively short. Hence, the long-term outcomes should be interpreted with caution. Third, our results may be influenced by the surgeons’ experience with laparoscopic ablation, which requires specialized training. Finally, there is no consensus on the selection criteria for ablation lesions at present, and this criterion is entirely determined by doctors on the basis of their experience.