Currently, surgical resection remains the preferred treatment for hepatic colorectal metastasis(10). For resectable patients, the 5-year survival rate with surgical treatment ranges from 25–40%(11). However, it remains uncertain whether different surgical approaches for potentially resectable patients with different clinical and pathological characteristics can improve survival outcomes. The purpose of this study was to explore the prognostic effects of different surgical treatment strategies for CLM patients through a retrospective analysis using the SEER database. Although retrospective analysis studies have certain limitations in terms of prospective comparisons of different surgical interventions (for example, in the cohort of 32,308 CLM patients in Table 1, we can only discern whether liver or colorectal cancer surgery was performed, but not whether patients underwent staged treatment or simultaneous treatment), we can still gain some insights from it.
Our study demonstrates that advanced age (≥ 65 yrs), female gender, Black race, colorectal primary site, CEA positivity, and higher N stage are risk factors associated with poor prognosis (Table 2A-2C). Interestingly, our analysis results indicate that compared to T1 stage, being at T2 or T3 stage does not seem to exacerbate the risk of poor prognosis. This finding is consistent with the analysis of Dakui Luo et al. regarding the prognostic value of stage IV colorectal cancer surgery (4). Contrary to our previous experience where tumor size has a clear relationship with prognosis(12), our current analysis results do not fully align. It appears that the size of the primary tumor does not have a positive correlation with prognosis in CLM patients. In light of this, we have made some speculations, suggesting that factors influencing prognosis also include the location of metastatic lesions(13). Even if the primary tumor is small, the prognosis may be significantly compromised if the metastatic lesions are attached to major vessels such as the portal vein. The possibility of small tumors possessing higher invasiveness lacks a definitive consensus, and currently, we are unable to draw further conclusions due to limited evidence.
In both univariate and multivariate Cox analyses of treatment modalities, patients who received surgical, radiation, or chemotherapy interventions showed lower hazard ratios (HR), indicating better prognosis. This study primarily discusses the prognostic value of different surgical approaches in CLM patients. From the survival analysis plots, it can be observed that patients who could tolerate both types of surgeries or underwent only one type of surgery had better overall survival (OS). It is possible to assume that patients with poorer physical conditions or more severe underlying diseases may not be suitable candidates for surgery, which would naturally result in worse OS. Moreover, patients who underwent only one type of surgery also have various clinical and pathological characteristics. Patients who only underwent colorectal cancer surgery may satisfy the indications for colorectal cancer surgery alone, while in the evaluation of liver cancer, the following conditions may be considered: (1) unresectable metastatic lesions, (2) lymph node metastasis around the porta hepatis and hepatic gallbladder area, (3) more than 4 liver metastases, (4) involvement of major branches of the portal and hepatic veins, and (5) remnant liver volume less than 30% of the original liver volume(14). Additionally, liver failure is considered an absolute contraindication for curative resection(11). Similarly, patients who only underwent liver cancer surgery may meet the indications for liver cancer surgery while the primary lesion is either unresectable or potentially resectable. These three scenarios may introduce selection bias in patient selection and lead to the conclusion that patients who underwent obvious treatment have better quality of survival. It is easy to understand that patients who are eligible for surgery have inherently favorable characteristics, including tumor growth status, making them more optimistic and suitable for resection, resulting in better prognosis compared to patients who did not undergo surgery.
Considering this, we performed propensity score matching to compare patients who received different surgical interventions with patients who did not undergo surgical intervention, in order to eliminate potential confounding factors related to the tumor itself and to align the two groups of patients as closely as possible at baseline. We still reached the conclusion that patients who actively participated in surgical removal treatment had significantly higher overall survival (OS) compared to those who did not receive surgical treatment (P < 0.001). Even when only one type of surgical treatment is performed, the study by Yong Sik Yoon et al. suggests that palliative resection seems to offer better survival rates than no surgery when the overall condition of patients allows for aggressive treatment, and they recommend the resection of the primary tumor regardless of disease severity(15). A single surgical intervention may not completely remove the tumor, but this treatment approach aims to maximize symptom relief. For these potentially resectable patients, precise and personalized treatment plans are advocated. For example, in cases where liver cancer is deemed unresectable but colorectal cancer is resectable, considering aggressive systemic therapy followed by resection of the primary tumor and subsequent targeted local treatment of metastatic lesions to alleviate symptoms can be considered(8).
Similarly, in cases where the primary tumor is unresectable but the metastatic lesions are resectable, considering palliative surgery and systemic therapy for the primary tumor while performing concurrent or staged resection of the metastatic lesions can be considered(8). Andrea Muratore MD et al. reported that the median survival of patients with unresectable disease who underwent two-stage liver resection was 38.3 months, whereas the median survival of patients who did not undergo the second-stage liver resection was 11.8 months, suggesting that personalized surgical strategies can still achieve curative resection in patients initially deemed unresectable(16). In the analysis results of this study, patients who underwent only one surgical intervention showed better prognosis compared to CLM patients with similar clinical and pathological characteristics who did not undergo surgery. This suggests that even if patients still retain tumor lesions, palliative removal of a portion of the tumor can have a certain therapeutic effect.
While developing personalized treatment strategies for patients with unresectable primary and/or metastatic lesions holds the potential to prolong patient survival, we still need to consider various factors, such as postoperative complications, postoperative ICU admission rate, postoperative infection rate, and so on(17). Ultimately, when deciding on the surgical approach, technical factors as well as the prognosis in terms of survival time and quality of life should all be taken into account.