# Removing the Primary Tumor, With or Without Liver Surgery, Is Linked to Longer Survival in Patients Whose Neuroendocrine Tumors Have Spread to the Liver

This systematic review and meta-analysis pooled 11 studies of 4,185 patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that had spread to the liver. Removing the primary tumor (with or without liver surgery) was linked to a 52% lower risk of death compared with no surgery (hazard ratio 0.48, 95% confidence interval 0.43–0.55, p<0.001). The benefit held up in sensitivity analyses and was seen in both pancreatic and gastrointestinal tumors. The authors stress that surgery should still be chosen case by case, because all included studies were retrospective.

# Removing the Primary Tumor, With or Without Liver Surgery, Is Linked to Longer Survival in Patients Whose Neuroendocrine Tumors Have Spread to the Liver

## Table of Contents

- Key Points
- Background: Why This Question Matters
- How the Researchers Conducted the Study
- Which Studies Were Included
- Which Patients Were Chosen for Surgery
- Anti-Tumor Drug Treatments Used
- Key Findings: Overall Survival
- Results by Tumor Location and Type of Surgery
- What These Findings Mean
- Limitations: What the Study Could Not Prove
- Recommendations for Patients
- Conclusion
- Frequently Asked Questions
- Source Information

## Key Points

- In 11 retrospective studies of 4,185 patients with gastroenteropancreatic neuroendocrine tumors and liver metastases, primary tumor removal was linked to a 52% lower risk of death versus no surgery.
- The pooled hazard ratio was 0.48 (95% CI 0.43–0.55), with low between-study heterogeneity and no evidence of publication bias.
- In five studies, combining primary tumor removal with liver resection gave a pooled hazard ratio of 0.35, the strongest survival advantage seen.
- Patients selected for surgery typically had well-differentiated G1 or G2 tumors, good performance status, and limited, resectable liver metastases.
- All included studies were retrospective, so selection bias is unavoidable and surgery decisions should be individualized by a multidisciplinary team.

## Background: Why This Question Matters

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are malignant tumors that start in neuroendocrine cells. These cells sit in the gastrointestinal tract and in related organs such as the pancreas. GEP-NETs are relatively uncommon, but their incidence has risen significantly in recent years.

These tumors are generally considered slow-growing (indolent). Even so, they are hard to diagnose, because their clinical symptoms are nonspecific. As a result, **40–50% of patients already have distant metastases (cancer that has spread) at the time of diagnosis**. The liver is the most frequent site where the cancer spreads.

Patients whose GEP-NETs have spread to the liver (liver metastases, or LM) typically have a poorer prognosis than patients without distant metastases. Drug therapy is currently the main treatment strategy for these patients. Available drug options include somatostatin analogues (SMA), molecular targeted therapy, and peptide receptor radionuclide therapy (PRRT).

Recent studies have explored whether removing the primary tumor (primary tumor resection, or PTR) helps these patients. Some studies looked at PTR alone. Others looked at PTR combined with liver resection (LR), which is surgery to remove liver metastases.

Guidelines do not fully agree. The European Society of Medical Oncology (ESMO) guidelines recommend PTR for patients with GEP-NETs and resectable liver metastases (metastases that can be surgically removed). The ESMO guidance suggests that PTR may extend overall survival (OS, the time from treatment until death from any cause).

However, the effectiveness of PTR remains uncertain. The latest European Neuroendocrine Tumor Society (ENETS) guidelines highlight that for small-intestinal NETs with metastatic disease, palliative or prophylactic PTR is controversial. The ENETS guidance states that the decision should be tailored to symptoms, metastatic burden, and multidisciplinary evaluation.

Some clinical studies also indicate that PTR in patients with advanced gastrointestinal neuroendocrine tumors (GI-NETs) does not significantly improve survival. For all these reasons, further research is needed. The key question is whether PTR, with or without liver resection, can effectively prolong overall survival in patients with GEP-NETs that have spread to the liver.

This systematic review and meta-analysis aimed to assess whether PTR, regardless of liver resection, offers a survival benefit for patients with GEP-NETs and liver metastases. The findings are intended to provide valuable insights for developing personalized treatment strategies.

## How the Researchers Conducted the Study

The researchers followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. They searched the PubMed and Embase databases for literature published over the past 20 years.

The search strategy combined three groups of terms:

- "liver Metastasis" OR "liver Metastases" OR "liver Metastatic"
- AND "neuroendocrine tumor"
- AND "surgery" OR "resection"

The search period ran from May 15, 2005, to May 15, 2025. The complete PRISMA-S checklist and the detailed search strategies are available in the article's Supplementary Tables 1 and 2.

The researchers set specific inclusion criteria. A study had to meet all of the following conditions:

1. The study involved patients with GEP-NETs and liver metastases.
1. The hazard ratio (HR) and its 95% confidence interval (CI) could be obtained, either directly or indirectly. A hazard ratio compares the risk of death between two groups over time.
1. The study compared overall survival between a surgical resection (PTR) group and a non-resection group.

Strict exclusion criteria were also established. The literature was limited to studies published in English. Meeting reports, guidelines, case reports, and review articles were excluded. Single-arm studies were not considered. If multiple publications reported on the same study population, only the publication with the most comprehensive statistical analyses and the highest quality assessment scores was included.

A PRISMA flow chart was constructed to illustrate the inclusion and exclusion process. The detailed PICOS criteria (Population, Intervention, Comparison, Outcomes, Study design) are provided in the article's Supplementary Table 3.

Two authors, Y.X. and Z.Z., independently extracted all abstracts and full texts. When they disagreed, a third author, J.L.L., was consulted for further evaluation. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Each study was independently evaluated by Y.X. and Z.Z. A NOS score of 6 or higher was considered to indicate high quality.

The primary outcome of this meta-analysis was the evaluation of overall survival between the PTR group and the non-resection group. A forest plot was generated to compare the hazard ratios of these two groups. The researchers also collected clinical data from the surgical cohort, including the type of surgery performed and the anti-tumor treatment regimens administered.

All statistical analyses were conducted in R (version 4.4.1; R Foundation for Statistical Computing, Vienna, Austria). For studies that did not report a hazard ratio, the researchers estimated the hazard ratio from Kaplan–Meier curves using the method of Tierney et al. They performed subgroup analysis by radical resection status and by tumor location.

Statistical significance was defined as P = 0.05, and all tests were two-sided. Heterogeneity (how much the studies differed from one another) was assessed with the I² statistic. An I² below 20% was considered negligible, and a fixed-effect model was applied. An I² between 20% and 50% indicated acceptable heterogeneity, and a random-effects model was used. Finally, funnel plots and Egger's test were used to evaluate potential publication bias.

## Which Studies Were Included

The preliminary search retrieved 1,525 records. Of these, 203 duplicates were removed. Title and abstract screening excluded 1,282 records, because they reported other tumor types or were systematic reviews, meeting abstracts, or guidelines.

Full-text review of the remaining 40 studies excluded 29 single-arm studies. Thus, **11 studies met the inclusion criteria and were included in the meta-analysis**. The study selection flow is shown in Figure 1 of the original article.

The 11 included studies are summarized in Table 1 of the original article. The table lists publication year, country, sample size, tumor location, surgical plan, inclusion period, and NOS score.

All 11 studies were nonrandomized cohort designs. Five studies used data from approved databases. The remaining studies were single-center or multi-center investigations. All studies were rated high quality. Five studies reported additional patient groups who underwent liver resection.

Surgical cohort sizes ranged from a minimum of 19 patients to a maximum of 1,289 patients. Three studies did not explicitly report a hazard ratio, so the researchers extracted hazard ratios from Kaplan–Meier curves.

The included studies, with their countries and surgical cohort sizes, were:

- Bettini et al. (2009), Italy, 19 of 51 patients underwent resection, pancreatic tumors, inclusion period 1990–2004, NOS score 7
- Partelli et al. (2015), Italy, United Kingdom, and Germany, 91 of 166 patients, pancreatic tumors, inclusion period 2000–2011, NOS score 7
- Bertani et al. (2017), Italy, 63 of 124 patients, pancreatic tumors, inclusion period 1994–2013, NOS score 8
- Tao et al. (2017), United States, 47 of 191 patients, pancreatic tumors, inclusion period 2010–2014, NOS score 7
- Lin et al. (2018), China, 35 of 63 patients, pancreatic tumors, inclusion period 1998–2016, NOS score 7
- Lewis et al. (2019), United States, 392 of 854 patients, gastrointestinal tumors, inclusion period 2005–2011, NOS score 7
- Zheng et al. (2019), United States, 897 of 1,547 patients, gastroenteropancreatic tumors, inclusion period 2010–2015, NOS score 7
- Gangi et al. (2020), United States, 1,289 of 1,954 patients, gastrointestinal tumors, inclusion period 2010–2015, NOS score 7
- Liu et al. (2023), China and United States, 55 of 155 patients, gastrointestinal tumors, inclusion period 2011–2021, NOS score 8
- Chen et al. (2024), United States, 1,139 of 2,320 patients, gastroenteropancreatic tumors, inclusion period 2016–2018, NOS score 8
- Xu et al. (2025), China, 93 of 163 patients, pancreatic tumors, inclusion period 1996–2019, NOS score 7

Several studies reported tumor grade data. Zheng et al. reported 726 grade 1, 310 grade 2, and 352 grade 3 tumors. Gangi et al. reported 992 grade 1, 302 grade 2, and 74 grade 3 tumors. Chen et al. reported 576 grade 2 tumors, with grade 1 and grade 3 not reported. Other studies reported smaller grade distributions, as listed in Table 1 of the original article.

## Which Patients Were Chosen for Surgery

Ten studies described the characteristics of patients who underwent primary tumor resection. Five of these studies found that younger patients were more likely to receive PTR than older patients.

Four studies reported that PTR recipients more often had primary tumors in the small intestine or colorectum. Several studies further noted that patients selected for PTR tended to have moderately to well-differentiated tumors. Tumor differentiation describes how much the cancer cells resemble normal cells; well-differentiated tumors are generally less aggressive.

For pancreatic primaries, PTR was more frequently performed when the tumor was in the pancreatic body or tail. When PTR was combined with liver resection, the liver metastases were typically confined to a single lobe and were small in size.

These patterns matter for interpreting the results. They show that surgeons selected patients with more favorable characteristics for surgery. This selection process can influence survival comparisons between surgical and non-surgical groups.

## Anti-Tumor Drug Treatments Used

Two studies provided detailed data on systemic therapy regimens for patients undergoing surgical resection. One of these studies also reported regimens for the non-resection group, covering 51 patients in total (19 in the resection group and 32 in the non-resection group).

In the resection group, somatostatin analogues (SMA) were the most common first-line therapy, used in 40.2% of patients. Chemotherapy was the next most common, used in 30.4% of patients. After disease progression, chemotherapy (12.5%) and peptide receptor radionuclide therapy (PRRT, 8%) were the preferred options.

In the non-resection group, SMA remained the favored treatment, used in 25.8% of patients. Lin et al. recommended systemic therapy for all patients, including octreotide, targeted agents, and/or systemic chemotherapy.

## Key Findings: Overall Survival

All included studies used hazard ratios to compare overall survival between patients who underwent PTR and those who did not. The meta-analysis found a **pooled hazard ratio of 0.48 for PTR recipients versus non-recipients (95% CI: 0.43–0.55, P < 0.001)**.

This result indicates a significant overall survival advantage for patients treated with PTR. In plain terms, the risk of death was about 52% lower in the surgery group than in the non-surgery group over the study periods. The confidence interval means that the true value is likely between 0.43 and 0.55. The P value below 0.001 means there is less than a 0.1% probability that this result occurred by chance alone.

Between-study heterogeneity was low (I² = 13%). This low value means the 11 studies produced reasonably consistent results. There was no evidence of publication bias (Egger's test P = 0.62). Publication bias occurs when studies with positive results are more likely to be published than studies with negative results.

Sensitivity analysis further confirmed the robustness of the result. When the researchers removed individual studies one at a time and recalculated the pooled estimate, the result did not materially change. This step-by-step removal tests whether any single study drives the overall finding.

## Results by Tumor Location and Type of Surgery

The researchers conducted a subgroup analysis by primary tumor site, comparing pancreatic tumors with gastrointestinal tract tumors. Because one subgroup showed an I² of 39%, they applied a random-effects model for this analysis.

For primary pancreatic neuroendocrine tumors (P-NETs), the pooled hazard ratio was **0.39 (95% CI, 0.27–0.56)**. For primary gastrointestinal neuroendocrine tumors (GI-NETs), the pooled hazard ratio was **0.51 (95% CI, 0.45–0.59)**.

The pooled hazard ratio for GI-NETs is numerically higher than that for P-NETs. However, the GI-NET subgroup exhibited virtually no heterogeneity (I² = 0%) and contributed a larger weight (62.2%) to the analysis.

Five studies compared overall survival between patients who received PTR plus liver resection and those who did not undergo resection. These results were pooled in a separate meta-analysis. The combined hazard ratio was **0.35 (95% CI, 0.29–0.43, P < 0.001)**.

This finding means that for patients with resectable liver metastases, adding liver resection to primary tumor resection did not compromise the survival benefit associated with PTR. In fact, the combined surgery group showed the strongest survival advantage in the analysis.

## What These Findings Mean

Because clinical symptoms are nonspecific, most patients with GEP-NETs are diagnosed at a late stage, often with distant metastases. Liver metastasis is more than ten times more likely than metastasis to other sites.

This high rate of liver spread is likely linked to the liver's anatomical features. The portal vein directly channels venous blood from the gastrointestinal tract to the liver. The hepatic sinusoids (small blood vessels in the liver) exhibit low shear stress from blood flow. These conditions facilitate tumor cell colonization in the liver, leading to implantation metastasis.

Clinically, metastasis to other locations is typically seen as an advanced stage, and surgical intervention is generally discouraged. This perception complicates surgical decision-making for patients with GEP-NETs and liver metastases. The role of surgery in patients with advanced GEP-NETs and distant metastases is debated.

Some studies suggest that PTR can reduce tumor burden, potentially extending patient survival even with liver metastases. Conversely, other research argues that PTR does not significantly improve overall survival compared to non-resection. That research also raises the possibility that surgery may increase mortality risk due to surgical complications. Given these clinical complexities, the researchers conducted this meta-analysis to evaluate the value and role of PTR in the treatment strategy for GEP-NETs.

Previous meta-analyses have examined the efficacy of palliative resection for midgut neuroendocrine tumors with unresectable liver metastases. This study, however, uniquely includes articles on radical resection. Palliative surgery is often performed in patients with unresectable liver metastases. Palliative surgery primarily aims to alleviate symptoms such as obstruction, bleeding, or hormonal imbalances, rather than providing a curative outcome.

In contrast, radical surgery involved both primary tumor resection and liver resection. Radical surgery was typically performed in patients with technically resectable liver metastases, aiming for curative intent. This study attempts to address a gap by including both surgical approaches. It offers a broader view of the potential benefits of surgery in patients with GEP-NETs and liver metastases.

Additionally, this study encompassed tumors located in the stomach and pancreas, further categorized by primary tumor location. By applying stringent exclusion criteria, the researchers excluded low-quality studies and incorporated recent literature. As one of the earliest meta-analyses to investigate surgical treatment for patients with GEP-NETs and liver metastases, this study demonstrated a significant survival benefit from PTR for these patients (HR = 0.48, 95% CI: 0.43–0.55, P < 0.001). When liver metastases are resectable, combining liver resection may enhance this survival advantage, but it should be considered only for highly selected patients.

Retrospective studies and international guidelines suggest that patients eligible for surgical treatment typically share several features:

- Well-differentiated G1 or G2 tumors
- Good performance status (the ability to carry out daily activities)
- A limited and resectable burden of liver metastases
- No uncontrolled extrahepatic disease (cancer outside the liver)

Symptomatic primary tumors often indicate the need for surgery. Examples include tumors that cause obstruction, bleeding, or hormone-related symptoms. However, these clinicopathological characteristics were not consistently reported in the studies reviewed. This inconsistency complicates the assessment of whether the observed survival benefits are due to the surgery itself or to selection bias. Selection bias occurs when patients with better health are more likely to receive a treatment.

To better identify patient subgroups that may benefit most from surgical management, further prospective studies are necessary. These studies need standardized reporting on metastatic burden, tumor grade, surgical intent, and symptom status.

The survival benefit observed may result from several mechanisms. First, resecting the primary tumor significantly reduces tumor burden and decreases the overall proliferative activity of tumor cells. This effect may slow the progression of liver metastases.

Second, a study by Bertani et al. suggests that PTR enhances the efficacy of PRRT for pancreatic neuroendocrine tumors with liver metastases. In that study, median overall survival extended from 65 to 112 months (P = 0.011).

Third, PTR can eliminate the source of liver metastases, alleviate symptoms like carcinoid syndrome, and improve systemic conditions. Carcinoid syndrome is a group of symptoms, including diarrhea and flushing, caused by hormones released by the tumor. Surgery-induced reductions in serotonin levels in patients with carcinoid syndrome can mitigate organ damage caused by symptoms such as diarrhea and flushing.

Fourth, the continued growth of the primary lesion may lead to severe complications. These complications include intestinal obstruction, gastrointestinal bleeding, or biliary obstruction. According to ESMO guidelines, PTR for small bowel neuroendocrine neoplasms reduces the risk of intestinal obstruction and improves patient prognosis. In cases of colorectal neuroendocrine neoplasms, palliative resection significantly lowers the risk of local infiltration and bleeding. This benefit applies even with liver metastasis, if the primary lesion is 4 cm or more in diameter. This surgery thereby prolongs survival.

The findings underscore the long-term benefits of surgical treatment over conservative management. Yet several critical issues warrant attention. Primarily, it is essential to identify which patients will benefit from surgery in terms of survival. Based on the reviewed articles, the researchers summarized several strategies for reference.

Numerous studies emphasize the importance of differentiating the primary tumor location. For instance, primary tumors in the pancreas often lead to severe postoperative complications, making resection generally inadvisable. However, in cases of distal pancreatectomy (surgery on the body or tail of the pancreas), the complications are typically manageable, making surgical intervention a viable option.

The decision to operate on high-grade tumors remains contentious. A recent consensus by the European Society of Endocrine Surgeons (ESES) advises cautious surgical exploration for patients with high-grade tumors. These perspectives may soon contribute to establishing a widely accepted standard for tumor resection.

## Limitations: What the Study Could Not Prove

This study has several limitations that patients and clinicians should weigh when interpreting the results.

First, the meta-analysis only included retrospective cohort studies. Retrospective studies look back at existing records rather than assigning treatments in advance. This design inherently carries a high risk of bias. The primary bias stems from missing critical information in most studies. Missing data included survival analysis data for the surgical resection group, reasons for non-resection, and details on drug therapies. These gaps can significantly impact treatment decisions and lead to variations in survival outcomes.

Second, all included studies used non-randomized designs, so selection bias is unavoidable. In clinical practice, surgical interventions are usually reserved for patients with better physical conditions, slower disease progression, and less aggressive tumors. Without proper statistical adjustments, selection bias can systematically skew study results. Although some studies attempted to mitigate this issue through statistical adjustments, the risk of bias persists. This risk could potentially undermine the research's effectiveness. Thus, there is an urgent need for randomized controlled trials to further validate the role of surgical resection.

Third, only three studies in this meta-analysis specifically reported overall survival results for patients with small intestinal NETs. Consequently, a more detailed subgroup analysis to differentiate the efficacy of PTR in pancreatic NETs versus small intestinal NETs is not feasible. As a result, the current subgroup findings primarily reflect data that combines small intestinal NETs with other GI-NETs. This combination may obscure site-specific differences.

Future studies should prioritize identifying the benefits and risks for patients undergoing PTR. These insights are vital for surgeons to make informed clinical decisions. This need is particularly important for elderly patients, who often have poor physical health and multiple chronic conditions. For these patients, determining whether surgical intervention will yield the desired clinical outcomes is a primary concern for surgeons when developing treatment plans. Conducting standardized studies to address these issues will ultimately result in more meaningful clinical outcomes.

## Recommendations for Patients

Based on this research, patients with GEP-NETs that have spread to the liver may want to discuss surgical options with their care team. The following points summarize what the evidence suggests and what questions may be worth raising.

1. Ask whether your primary tumor and liver metastases can be surgically removed. The survival benefit in this analysis was strongest when both the primary tumor and liver metastases were removed (hazard ratio 0.35).
1. Ask about your tumor grade and differentiation. Patients selected for surgery in these studies typically had well-differentiated G1 or G2 tumors.
1. Ask about your overall health and performance status. Surgical decisions in the reviewed studies favored patients with good physical condition and no uncontrolled cancer outside the liver.
1. Ask whether your primary tumor is causing symptoms. Tumors causing obstruction, bleeding, or hormone-related symptoms often indicate a need for surgery.
1. Ask about the location of your primary tumor. The survival benefit appeared in both pancreatic and gastrointestinal tumors, though the size of the benefit differed between the two groups.
1. Ask about combining surgery with other treatments. One reviewed study found that removing the primary tumor improved the effectiveness of peptide receptor radionuclide therapy (PRRT) in pancreatic tumors with liver metastases.

Because all included studies were retrospective, the decision to operate should be individualized. The authors state that decisions should be based on patient and tumor characteristics. A multidisciplinary team, including surgeons, oncologists, and other specialists, should be involved in this decision.

## Conclusion

In conclusion, patients with GEP-NETs and liver metastases appear to derive a survival benefit from primary tumor resection compared with conventional therapy. However, clear selection criteria are needed to identify which patients will truly benefit from a surgical approach. In addition, synchronous liver resection in patients with resectable liver metastases may further enhance this survival advantage.

## Frequently Asked Questions

### Can removing the primary tumor help if my neuroendocrine tumor has spread to my liver?

A review of 11 studies of 4,185 patients with gastroenteropancreatic neuroendocrine tumors and liver metastases found that removing the primary tumor, with or without liver surgery, was linked to a 52% lower risk of death compared with no surgery. The benefit appeared in both pancreatic and gastrointestinal tumors, but all included studies were retrospective.

### Does it help to remove liver metastases at the same time as the primary tumor?

Five of the reviewed studies compared patients who had primary tumor removal plus liver resection with those who had no resection. Their combined hazard ratio was 0.35, meaning the strongest survival advantage appeared in the combined surgery group. This option was considered only for patients whose liver metastases were resectable.

### Who was chosen for surgery in these studies?

Patients selected for surgery tended to be younger, have well-differentiated G1 or G2 tumors, good performance status, liver metastases confined to one lobe and small in size, and no uncontrolled cancer outside the liver. These patterns show surgeons selected patients with more favorable characteristics, which can influence survival comparisons between surgical and non-surgical groups.

### What are the limitations of this evidence?

All 11 included studies were retrospective and non-randomized, so selection bias is unavoidable. Many studies were missing data on survival, reasons for non-resection, and drug therapies. Only three studies specifically reported overall survival for small intestinal tumors, so site-specific differences could not be fully separated. Randomized controlled trials are still needed to confirm the role of surgery.

### What should I ask my care team about surgery?

Ask whether your primary tumor and liver metastases can be surgically removed, and about your tumor grade, differentiation, overall health, and performance status. Ask whether your primary tumor is causing symptoms such as obstruction, bleeding, or hormone-related symptoms. Because all included studies were retrospective, decisions should be individualized by a multidisciplinary team including surgeons and oncologists.

### Can surgery be combined with drug treatments?

Two reviewed studies reported systemic therapy details. In the resection group, somatostatin analogues were the most common first-line therapy, used in 40.2% of patients, followed by chemotherapy in 30.4%. One reviewed study found that removing the primary tumor improved the effectiveness of peptide receptor radionuclide therapy in pancreatic tumors with liver metastases.

### I have a gastroenteropancreatic neuroendocrine tumor that has spread to my liver and surgery has been suggested — when should I get a second opinion?

Removing the primary tumor, with or without liver surgery, was linked to a 52% lower risk of death (hazard ratio 0.48), and the benefit was strongest when both the primary tumor and liver metastases were removed (hazard ratio 0.35). Because all included studies were retrospective, surgery should be chosen case by case, based on tumor grade, differentiation, performance status, liver metastasis burden, and symptoms. A second opinion can help confirm whether you fit the characteristics of patients selected for surgery in these studies. Diagnostic Detectives Network provides independent expert second opinions.

## Source Information

**Original article title:** Resection of the primary tumor with or without liver resection reduces the risk of death in patients with liver metastatic gastroenteropancreatic neuroendocrine tumors: a systematic review and meta-analysis.

**Authors:** Yue Xiao, Jianli Wang, Zejin Zhao, Luya Wen, Jian Li, and Jinlong Liu.

**Author affiliations:** Department of Hepatobiliary Surgery, The Affiliated Hospital of Chengde Medical University, Chengde, Hebei, China; and Hebei Key Laboratory of Panvascular Diseases, Chengde, Hebei, China.

**Journal:** Frontiers in Oncology, volume 15, article 1693647.

**Publication details:** Received 30 September 2025; revised 08 December 2025; accepted 26 December 2025; published 14 January 2026. DOI: 10.3389/fonc.2025.1693647.

**Article type:** Systematic Review.

**Funding:** Natural Science Foundation of Hebei Province (Grant No. H2025406008).

**Conflicts of interest:** The authors declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

*This patient-friendly article is based on peer-reviewed research.*


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