This study analyzed a total of 21,928 patients diagnosed with colorectal cancer, pancreatic cancer, breast cancer, and gastric cancer, which are most prone to liver metastasis, to identify the factors that affect the benefit of PTR. In this analysis, the application of PSM reduced the selection bias between the surgery and non-surgery groups. By analyzing the clinicopathological characteristics and using logistic regression, we determined the factors associated with surgical benefits. Additionally, a nomogram was developed specifically for patients with CRLM to help identify suitable candidates for PTR. Internal and external validation ultimately confirmed the reliability of the nomogram in predicting the benefit of PTR.

PTR can reduce tumor-related complications and avoid life-threatening situations. Previous studies have shown that PTR can prolong the survival time of patients with liver metastatic cancer, including colorectal cancer, pancreatic cancer, gastric cancer, and breast cancer.7,8,9,10 According to Paget’s seed and soil theory,11 cancer cells will spread throughout the body circulation when distant metastasis is detected. Therefore, local treatment will not affect the OS rate.12 However, there are several other theories that explain the basic principle that PTR increases the OS of stage IV cancer patients. By removing the primary site tumor and reducing the number of tumor cells, the prognosis of patients can be affected.13 Removing the primary tumor can reduce the volume of cancer stem cells, thereby improving the efficacy of systemic treatment by reactivating the autoimmune system.14 Additionally, the concept of ‘cell vaccination’ indicates that cancer cells released from the primary tumor into the bloodstream will return to the primary tumor and be activated.15 These hypothetical mechanisms are all based on basic experimental results; therefore, it is of extreme importance to demonstrate these results clinically.12

Multiple studies have shown that the removal of primary lesions is an important factor affecting OS. A study conducted in Canada targeting stage IV colorectal cancer patients found that OS in the surgery group was significantly longer than that in the non-surgery group (27 months vs. 14 months).16 In the past decade, the surgical safety of pancreatic cancer has continuously improved, with a mortality rate of <5%, leading to the expansion of local surgical methods for the pancreas. Multiple studies have shown that the median survival time in the surgery group for M1-stage pancreatic ductal adenocarcinoma at the primary site is significantly higher than that in the non-surgery group.8 A randomized controlled trial in Turkey showed that PTR, as an initial treatment for newly diagnosed stage IV breast cancer, significantly improved the OS rate. Furthermore, by analyzing the data of 714 patients in three randomized controlled trials, a meta-analysis showed that PTR in stage IV breast cancer also significantly improved the OS rate.7 Müsri et al. conducted a retrospective analysis of 288 patients with metastatic gastric cancer and concluded that PTR can prolong the median OS of patients (12.0 months vs. 7.8 months).10 These various studies all indicate that PTR can improve the survival of patients with primary tumor metastases, which is partially consistent with our research findings.

For patients with liver metastases, PTR significantly affects survival time and is associated with prognosis. To maximize the effectiveness of surgical treatment, it is important to develop the most appropriate treatment strategy using chemotherapy, surgery, and radiotherapy, alone or in combination.12 Due to the potential imbalance in covariate distribution between the surgery and non-surgery groups, there exists a risk of selection bias, with significant heterogeneity observed in clinical data such as age, primary site, and tumor stage. Therefore, 1:1 PSM was employed between the surgery and non-surgery populations to mitigate these mismatches in other clinical information. On this basis, we further investigated the factors that affect surgical benefit. Our research indicates that combining chemotherapy with PTR can result in an improved prognosis for patients with PLM. Chemotherapy after surgical resection is the first-line treatment for PLM patients.17 The statistical analysis for GLM patients indicated that performing PTR improved the median CSS, although the difference was not statistically significant. A study by Al-Batran et al.18 showed that patients with localized metastatic gastric cancer who received neoadjuvant chemotherapy and underwent surgery showed good survival rates. The median OS time for patients undergoing surgery combined with chemotherapy was 31.3 months, while that of patients receiving chemotherapy only was 15.9 months. Clinical experience shows that PTR for breast cancer can effectively relieve chest symptoms, such as bleeding, ulcers, and pain caused by invasion of the chest wall.19,20,21,22,23,24 Neoadjuvant chemotherapy for operable breast cancer can reduce neoplasm staging as well as axillary lymph node metastasis,25 thus improving the cosmetic effect and reducing the incidence rate of surgery. Some studies have shown that factors such as ‘complete resection of primary tumor’, ‘new metastasis’, and being ‘young’ indicate that patients are suitable candidates for breast cancer PTR,21,22 which is consistent with some of our research results. Our study further confirms that factors associated with PTR benefits in BLM include younger age, race, and receiving radiotherapy.

In patients with CRLM, there are several factors that affect the benefits of PTR. Personalized clinical decisions should be made with comprehensive consideration. From an embryological perspective, the view that the OS of left colorectal cancer patients is greater than that of right colorectal cancer patients has been widely proven and explained. They have different origins, therefore they have differences in incidence,26,27 in clinical, endoscopic and histological appearances,28,29 and in some molecular characteristics.30,31 It is obvious that patients with liver metastases from right colon cancer have the worst survival rate and the least chance of benefiting from surgery in our study. The results show that patients with younger age, lower pathological grade, and N1 stage are more eligible for surgery. Based on these significant variables, we developed a nomogram for CRLM patients that significantly enhances clinical utility. Furthermore, the nomogram also performed well in both internal and external validation.

This study has some limitations. This was a retrospective study based on the SEER database, which introduces inherent biases, such as the absence of detailed information on treatment and complications, number of liver metastases, and molecular profiling. PSM has minimized these differences between groups but it lacks specific details regarding the type and duration of chemotherapy and radiotherapy. Therefore, we can only classify patients as receiving chemotherapy, radiotherapy, or ‘none/unknown’, potentially introducing bias.