The lung is the second most common site for metastases from colorectal cancer [1]. Surgical metastasectomy is the preferred option when complete resection is feasible, and multiple studies have demonstrated promising survival outcomes for selected patients [2]. The increasing prevalence of metastasectomy has been driven by high-volume institutions, where patients experience low postoperative morbidity and mortality rates during inpatient care [3]. Stereotactic ablative radiotherapy (SABR) was initially introduced for medically inoperable patients or those who declined surgical resection [4]. SABR is a non-invasive technique that administers a high dose per fraction, typically in 1-5 sessions, using highly conformal beams to ablate the tumor while minimizing toxic effects to surrounding organs. The use of SABR for oligometastatic disease (OMD) has significantly increased, particularly in centers where surgeons routinely perform metastectomies at their institutions [5].

In patients with colorectal cancer and lung metastases, the PulMiCC trial was the first randomized clinical trial that compared surgical metastasectomy with continued active monitoring [6]. The trial was halted early due to poor and declining recruitment, and the small number of study participants precluded a conclusive analysis. Contrarily, the SABR-COMET trial, a landmark study, showed that SABR improves overall survival (OS) in patients with OMD from various histologies and metastatic sites [7], prompting further research, including histology-specific and phase 3 trials [8]. Since the publication of the SABR-COMET trial results, establishing clinical equipoise has become challenging, which complicates the initiation of similar randomized trials like the PulMiCC trial, particularly in metastatic colorectal cancer (mCRC) where local therapy for liver metastases is already well established [9].

Despite the lack of level I evidence, one of the clinically relevant questions in managing lung metastases from mCRC in clinics extends beyond the choice of whether to apply local therapy; it crucially involves selecting the optimal local therapy modality. To date, no completed randomized trials are comparing different local therapy modalities for pulmonary metastases, which leaves a significant gap in evidence-based guidance for treating physicians. Thus, this study aims to compare the effectiveness of SABR versus surgical metastasectomy in terms of local control, oncologic outcomes, and treatment-related toxicity.

In addressing the role of local therapies for pulmonary metastatic disease, one of the highly relevant questions is identifying the most suitable local modality for treating these patients [13]. In this single, large institutional, retrospective comparative study involving 404 patients with 528 pulmonary metastases, we evaluated the treatment outcomes of surgery and SABR as local therapies. Our study demonstrated that SABR was able to achieve excellent local control comparable to surgery, with both groups showing well-tolerated treatments, and low morbidity rates without mortality. A unique aspect of our study is the differentiation based on treatment intent in RT, specifically whether an ablative dose was administered, akin to the distinction between R0 and R1/2 resection in surgery. In cases with multiple lesions or when the treatment intent was to extend the efficacy of systemic therapy for the oligoprogression concept [14], dose-reduced, non-ablative doses (typically a BED less than 100 Gy, such as 30 Gy in 5 fractions or 24 Gy in 3 fractions) can be utilized (S4 Table). As expected, high-dose palliative RT exhibited significantly lower local control rates than the surgery and SABR groups (S5 Fig.).

Our findings regarding local control are in line with the evidence that higher SABR doses, typically with a BED ≥ 100 Gy, result in significantly better local control rates for lung metastases compared to lower doses [15,16]. Guckenberger et al. [17] found that the dose-response curve for local control plateaus around a BED of 100 Gy. This aspect has not been generally properly accounted for in comparative studies between surgery and SABR, leading to the biased conclusion that SABR is inferior to surgery in terms of local control [18].

Another important finding of our study is the significant differences in baseline characteristics selecting RT and surgery for local therapy. Surgery was frequently used upfront when lung metastases were first diagnosed, particularly when the metastases were small, solitary, and without other site metastases. This preference for surgery can be explained by its known advantages over SABR, such as providing a definitive pathological assessment, the potential for complete tumor removal, and eliminating the need for extensive radiologic surveillance [19,20]. Meanwhile, RT was often administered after upfront chemotherapy, typically around one year later, and was preferred for larger tumors, multiple lesions, or when patients had mediastinal lymph node metastases or extrapulmonary disease burden, reflecting the higher risk of disease progression after local therapy as shown in decreased PFS and OS compared to surgery. Furthermore, patients might often be exhausted from previous treatments, such as multiple surgeries or prolonged chemotherapy, and are likely to be inclined towards the minimally invasive nature and shorter recovery time of RT compared to surgery.

If a patient is considered a good candidate for local therapy via multidisciplinary discussion, selecting the best local therapy with the maximized therapeutic index is often not straightforward and involves a significant degree of subjective judgment. For SABR, the proximity of critical organs at risk (e.g., trachea, main bronchus, heart, esophagus, stomach) is a primary consideration, as this can compromise dose coverage planning [21]. In terms of toxicity, the respiratory motion is more significant in the lower lobe than in the upper lobe [22], potentially increasing the irradiated volume, and the availability of respiratory control techniques to reduce the irradiated volume (e.g., gating or tracking) can be a key consideration, especially treating multiple lesions. For surgery, several key factors are generally considered to ensure the best possible outcomes, including palpability, localization, extent of resection, general health, and pulmonary function [13]. Although unavailable at our institution, interventional radiology treatments such as microwave ablation and radiofrequency ablation are also known to control lesions effectively, depending on their location and size [23]. In this context, although there is no widely accepted treatment algorithm, the multidisciplinary approach remains paramount for treatment selection, especially with the active involvement of all local therapy stakeholders to compare the risk/benefit ratio of different modalities [24]. Our findings could provide valuable insights into clinical decision-making in these cases.

Our finding that many patients received subsequent local therapy for recurrent pulmonary metastases has important implications. In well-known oligometastases trials, this figure is around 10%-20% [7,25], and it is expected to be higher in cases of mCRC. Since, unlike the liver, the lung lacks regenerative capacity and has limited pulmonary reserve, it is crucial to prioritize preserving pulmonary reserve, considering that these patients may require multiple treatments.

Our study has several inherent limitations due to its retrospective nature. As shown in the baseline characteristics, selection bias exists between the treatment groups. Despite adjusting for several important factors, significant differences by treatment groups in PFS and OS remain. However, the possibility that more favorable tumors were treated with SABR is low; instead, there is a selection bias towards treating more unfavorable tumors with SABR. The difference in follow-up duration between the treatment groups, with a shorter median follow-up for the SABR group, may limit the ability to fully assess long-term outcomes, highlighting the need for extended follow-up in future studies. Considering these points, the finding that SABR provides equally excellent local control and low overall toxicity compared to surgery is unlikely to change. The fact that our institution is a large-volume single center with experienced surgeons and radiation oncologists can also introduce selection bias, and caution is needed when generalizing these results to low- to intermediate-volume centers. Institutional experience has also been recently suggested to influence SABR’s local control outcomes [26], similar to the relationship between volume of experience and surgical outcomes [27]. Since systemic therapy was administered heterogeneously and RT timing varied, elucidating potential interactions between systemic therapy and local control/toxicity to identify the pure component of local therapy was not feasible. Local progression was not pathologically confirmed, but additional positron emission tomography–CT results and monitoring through more than two serial follow-ups were used to determine disease progression. Considering SABR is generally less effective for larger tumors, the small number of patients with large tumor sizes in this study, due to the 3-month short-term image follow-up and early referral, must be taken into account, and thus the results should not be extrapolated to lesions with larger tumor sizes. Our study cannot address whether local therapy confers a survival benefit, or which patients are best suited for local therapy.

In conclusion, we found SABR can achieve excellent local control outcomes similar to surgery. Given the practical difficulty of conducting randomized trials comparing these two modalities for lung metastases, our findings provide important clinical implications. Since patients may require multiple treatments, a patient-centered approach is essential, aiming to preserve lung reserve and minimize morbidity risk while achieving local control. Continued multidisciplinary collaboration within all available local therapy modalities is needed to determine the best local modalities for different situations and locations, understanding the pros and cons of each treatment. With successful collaboration, a hybrid approach, which is not uncommon in the management of liver tumors, could also be investigated for multiple lung lesions [28].