Abstract
The optimal number of examined lymph nodes (ELNs) for colon cancer (CC) remains controversial. This study aims to identify patient-specific factors associated with the number of ELNs retrieved in CC patients undergoing hemicolectomy and to explore the potential for establishing a minimum ELNs threshold based on patient characteristics. We retrospectively analyzed data on patients with stage I-III CC from two sources: the Chinese Multi-Institutional Registry (CMIR, N = 10,367; 2010–2018) and the Surveillance, Epidemiology, and End. Results (SEER) database (N = 121,216; 2010–2018). Logistic regression modeling was used to identify patient-specific factors associated with ELN counts. Eight distinct patient cohorts were constructed, and the relationship between ELNs and overall survival (OS) was assessed using restricted cubic spline (RCS) curves and Kaplan-Meier curves. This study was registered with the ChiCT Registry (ChiCTR2400084767). The median ELN count was 16 (IQR 12–22) in the SEER cohort and 15 (IQR 12–20) in the Chinese cohort. Age, tumor size, and location emerged as key factors influencing ELN numbers. Notably, the optimal ELN thresholds for optimal survival across all eight cohorts ranged from 14 to 17, exceeding the current recommendation of 12. Exceeding these cohort-specific thresholds was associated with significantly improved OS in both databases (all P < 0.001). The detailed comparison of ELN-related statistics between the two databases is shown in Supplementary Table X. The present study reveals heterogeneity in the minimum ELN requirements across different patient cohorts with CC. Further prospective studies and randomized controlled trials are warranted to validate these tailored thresholds and inform guideline updates.
Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-026-35171-8.
Keywords: Heterogeneity, Examined lymph nodes, Colon cancer, Hemicolectomy
Subject terms: Epidemiology, Epidemiology
Introduction
Colorectal cancer (CRC) remains a significant global health burden, with surgical resection serving as the mainstay of treatment for patients diagnosed with early-stage disease1. Accurate cancer staging is crucial for guiding post-operative treatment decisions and predicting long-term survival outcomes. The American Joint Committee on Cancer (AJCC) TNM staging system is the gold standard for CRC, incorporating tumor size (T), lymph node involvement (N), and distant metastasis (M) to classify disease severity2.
Within the TNM system, lymph node examination is particularly critical in determining the extent of disease spread and guiding treatment decisions. The number of examined lymph nodes (ELNs) directly impacts the detection of metastatic spread, which in turn influences pathological N-staging and ultimately affects patient prognosis3. Pathologists recommend a minimum of 12 ELNs be evaluated for optimal staging in CRC patients according to the College of American Pathologists (CAP) guidelines4. Several factors may affect the achievement of this minimum number of ELNs, including the type and extent of surgical removal, the location of the tumor, neoadjuvant treatment (in rectal cancer, radiation is commonly used and may affect the number of lymph nodes examined), the capabilities of the treating hospital, and the specific pathology procedures used5,6. Current research on the optimal number of ELNs in CRC remains inconclusive, with conflicting findings and limitations such as small sample sizes in prior studies7,8. A minimum of 15 ELNs was recommended for patients undergoing surgery for rectal cancer in our previous large sample study9. However, patient-specific factors influencing the optimal number of lymph nodes examined in colon cancer patients undergoing hemicolectomy have not been confirmed in extensive sample data. Moreover, the optimal number of ELNs that could predict long-term overall survival in different patient cohorts has not been reported.
This study aimed to address these knowledge gaps by harnessing the extensive data resources of the Chinese Multi-institutional Registry (CMIR) and the Surveillance, Epidemiology, and End Results (SEER) database.
Methods
We investigated patient-specific factors associated with the number of ELNs retrieved following hemicolectomy in colon cancer. Subsequently, distinct patient cohorts were constructed based on the identified risk factors. We determined the optimal number of ELNs required for each cohort’s long-term survival. Finally, the generalizability of our SEER-derived findings was assessed by analyzing a large, independent patient cohort from China.
Data sources and collection
We retrospectively collected data from the CMIR, encompassing five tertiary hospitals in China. The timeframe spanned from January 2010 to December 2018, capturing a diverse patient population. Data points for each patient included demographics (age, gender, diagnosis year), tumor characteristics (size, location, histological type, differentiation), ELNs retrieved and positive ELNs, surgical resection modality, treatment details, and follow-up outcomes (survival status and duration). Moreover, we leveraged the Surveillance, Epidemiology, and End Results (SEER) database, a comprehensive source of population-based cancer registry data in the United States. Data for CRC patients diagnosed between January 2010 and December 2018 was extracted using SEER*Stat Version 8.1.5. This data included demographics, tumor characteristics, surgical resection modality, TNM classification, and survival information. Lymph node examination followed established protocols, with at least two pathologists confirming the number of positive nodes. Tumor staging adhered to the 7th edition of the AJCC TNM classification for CRC. Ethical approval for this study was granted by the Ethics Committee of Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences (Approval number: KY-2024063).
Inclusion and exclusion criteria
Patients with CRC aged > 18 years who underwent surgical treatment were included. Patients were excluded if: (1) missing information on age or gender; (2) missing information on the tumor (e.g., size, location, number of ELNs); (3) treated with pre-operative radiotherapy or chemotherapy (as pre-operative chemotherapy or radiotherapy affects the number of ELNs); and (4) missing follow-up information. All patients in this study were followed up by telephone or a review of their medical records.
Statistical analyses
Continuous variables were expressed as medians with interquartile ranges (IQRs). Categorical variables were presented as frequencies. Factors including age (categorized as > 65 years vs. 18–65 years), tumor size (categorized as ≥ 5 cm vs. < 5 cm), tumor location (right vs. left), sex (male vs. female), AJCC stage (T3/T4 vs. T1/T2), and grade (Poor/Undifferentiated vs. Well/Moderate) were analyzed using univariable logistic regression to assess their association with achieving a minimum of 12 ELNs. Factors deemed statistically significant in the univariable analysis were then included in a multivariable logistic regression model to identify independent predictors for reaching the 12-ELNs threshold.
Eight distinct patient cohorts were constructed based on the three patient-specific factors identified in the two databases. Within each cohort in the SEER database, we investigated the optimal number of ELNs required for a better overall survival prognosis. The optimal ELNs thresholds established within the SEER-derived cohorts were then evaluated for their validity in the large sample of Chinese data from the multi-institutional registry.
The study employed the Kaplan–Meier method to estimate the 5-year OS of the patient cohorts. The log-rank test was utilized to assess statistically significant differences in OS between groups. A Cox proportional hazards regression model was implemented to investigate the independent effect of ELNs on OS. This model was further adjusted for other prognostic factors such as age, tumor stage, tumor location, grade, and tumor size. Additionally, the relationship between ELNs and OS was evaluated continuously using restricted cubic splines (RCS) within a multivariable Cox model. Three knots were strategically placed at the 10th, 50th, and 90th percentiles of the ELNs distribution. The application of RCS offers a robust approach for analyzing the non-linear relationship between continuous variables and survival outcomes. Notably, RCS enable the identification of potential inflexion points within the risk function, which may represent clinical thresholds for ELN’s impact on survival. These breakpoints were then considered as potential thresholds for clinical significance. Kaplan–Meier curves were generated to depict covariate-adjusted survival estimates to assess the effect of ELNs on long-term survival while accounting for potential confounders. This approach allowed for the visualization of 5-year survival probabilities stratified by ELN count, while simultaneously controlling for the influence of other factors such as age, tumor stage, location, grade, and size. All statistical analyses were conducted using R software (version 4.0.4; http://www.r-project.org). A p-value of less than 0.05 was considered statistically significant.
Results
Patient characteristics and distribution of ELNs
A total of 131,583 patients with colon cancer were included in this retrospective analysis, drawn from two separate cohorts: the SEER database (n = 121,216) and the CMIR (n = 10,367). The case screening process in both databases is shown in Supplementary Fig. 1. All patients met the pre-defined eligibility criteria. The baseline characteristics of each database are presented in Table 1. In the CMIR, 56.50% (5857/10,367) were men, while the SEER cohort had a slightly lower proportion of men at 48.47% (59,077/121,216). The distribution of ELNs counts, as illustrated in Fig. 1, demonstrated a high degree of consistency between the two cohorts. The median ELNs count in the Chinese cohort was 15 (IQR 12–20), while the SEER cohort had a median of 16 ELNs (IQR 12–22). At least 12 lymph nodes (LNs) were examined in 72.34% (7500/10,367 patients) and 71.92% (87,178/121,216 patients) of the Chinese and SEER cohorts, respectively, consistent with the median ELN counts (15 vs. 16). The detailed comparison of ELN-related statistics (sample size, median ELN, IQR, percentage of ELN ≥ 12, percentage of ELN ≥ 14) between the two databases is shown in Supplementary Table X.
Table 1.
Baseline patient characteristics in the two databases.
| SEER database N (%) | China database N (%) | |
|---|---|---|
| Total | 121,216 (100%) | 10,367 (100%) |
| Sex | ||
| Male | 59,077 (48.74%) | 5857 (56.50%) |
| Female | 62,139 (51.26%) | 4510 (43.50%) |
| Age, years | ||
| < 65 | 47,305 (39.03%) | 6323 (60.99%) |
| ≥ 65 | 73,911 (60.97%) | 4044 (39.01%) |
| Grade | ||
| Well/moderate | 97,441 (80.39%) | 8916 (86.00%) |
| Poor/undifferentiated | 23,775 (19.61%) | 1451 (14.00%) |
| Tumor size, median cm (IQRs) | 4.0 (3.0–6.0) | 4.5 (3.5–6.0) |
| Location | ||
| Right | 77,466 (63.91%) | 6168 (59.50%) |
| Left | 43,750 (36.09%) | 4199 (40.50%) |
| AJCC stage | ||
| Ⅰ/Ⅱ | 75,542 (62.32%) | 6428 (62.00%) |
| Ⅲ | 45,674 (37.68%) | 3939 (38.00%) |
| T stage | ||
| T1/2 | 33,989 (28.04%) | 1659 (16.00%) |
| T3/4 | 87,227 (71.96%) | 8708 (84.00%) |
| N stage | ||
| N0 | 75,542 (62.32%) | 6428 (62.00%) |
| N1/2 | 45,674 (37.68%) | 3939 (38.00%) |
| ELNs count, median (IQRs) | 16 (12–22) | 15 (12–20) |
AJCC, American Joint Committee on Cancer; T, tumor size; N, lymph node involvement; ELNs, examined lymph nodes; IQRs, interquartile ranges; SEER, Surveillance, Epidemiology, and End Results; cm, centimeter.
Fig. 1.
The distribution of examined lymph node (ELN) counts in patients with colon cancer who underwent hemicolectomy from two independent databases: the Chinese Multi-Institutional Registry (CMIR) and the Surveillance, Epidemiology, and End Results (SEER) program.
Univariable and multivariable logistic regression analysis
Univariable analysis of SEER and CMIR revealed several factors significantly associated with ELNs count (p < 0.05). These factors included age, tumor size, tumor location, AJCC T-stage, and tumor grade. Subsequent multivariable logistic regression analyses within each database demonstrated that age, tumor size, tumor location, AJCC T-stage, and tumor grade remained significant independent predictors of ELNs count (p < 0.05). Table 2 shows the results of both univariable and multivariable logistic regression analyses.
Table 2.
Univariate and multivariate logistic regression analysis for factors associated with 12 examined lymph nodes (ELNs) threshold in two databases.
| Parameter | At risk group | SEER database | China database | |||||
|---|---|---|---|---|---|---|---|---|
| Positive | Negative | OR | 95% CI | p-value | OR | 95% CI | p-value | |
| Significant factors in univariate analysis | ||||||||
| Age | ≥ 65 | <65 | 1.74 | 1.69–1.78 | <0.001 | 1.20 | 1.03–1.28 | <0.001 |
| Tumor size | ≥ 5 | <5 | 1.92 | 1.87–1.97 | <0.001 | 3.01 | 2.69–3.37 | <0.001 |
| Tumor location | Right | Left | 1.75 | 1.71–1.80 | <0.001 | 1.88 | 1.72–2.05 | <0.001 |
| Sex | Male | Female | 0.89 | 0.87–0.92 | <0.001 | 0.94 | 0.86–1.03 | 0.19 |
| AJCC T stage | T3/T4 | T1/T2 | 1.59 | 1.54–1.63 | <0.001 | 2.22 | 2.17–2.27 | <0.001 |
| Grade | Poor/undifferentiated | Well/moderate | 1.24 | 1.20–1.28 | <0.001 | 1.43 | 1.26–1.63 | <0.001 |
| Stepwise multivariate logistic analysis | ||||||||
| Age | ≥ 65 | <65 | 1.35 | 1.28–1.42 | <0.001 | 1.27 | 1.20–1.35 | <0.001 |
| Tumor size | ≥ 5 | <5 | 1.68 | 1.64–1.73 | <0.001 | 2.55 | 2.27–2.86 | <0.001 |
| Tumor location | Right | Left | 1.26 | 1.20–1.32 | <0.001 | 1.64 | 1.50–1.80 | <0.001 |
| Sex | Male | Female | 0.93 | 0.90–0.95 | <0.001 | NA | NA | NA |
| AJCC T stage | T3/T4 | T1/T2 | 1.31 | 1.27–1.35 | <0.001 | 1.85 | 1.79–1.91 | <0.001 |
| Grade | Poor/undifferentiated | Well/Moderate | 1.02 | 0.98–1.06 | 0.26 | 1.11 | 0.97–1.28 | 0.12 |
OR, odds ratio; CI, confidence interval; SEER, Surveillance, epidemiology, and end results.
Stratification of patient cohorts
To account for potential heterogeneity within the study populations, we stratified patients from both databases into eight distinct cohorts based on three critical patient-specific factors: age (≥ 65 or < 65 years), tumor location (left or right colon), and tumor size (≥ 5 cm or < 5 cm). Within the SEER database, the largest patient cohort (38,227 patients, 31.54%) comprised individuals aged 65 years or older, with tumors smaller than 5 cm located in the right colon. In contrast, the Chinese database revealed the largest cohort (2392 patients, 23.07%) to be patients younger than 65 years old with tumors 5 cm or larger located in the right colon. The specific proportions and number of patients within each cohort are detailed in Supplementary Table 1.
Optimal ELNs threshold in each patient cohort of the SEER database
To comprehensively assess the non-linear association between ELNs count and overall survival risk in the SEER database, we employed a Cox proportional hazards model with restricted cubic splines. This approach allowed for flexible modelling and visual depiction of the relationship while adjusting for potential confounders such as age, tumor stage (T stage), tumor grade, location, and size. Across all eight cohorts within the SEER database, a distinct “threshold” ELNs count emerged. Below this threshold, the risk of death significantly decreased with increasing ELNs count. Beyond the threshold, the risk of death plateaued, exhibiting a comparatively stable risk profile thereafter, which suggested a statistically significant non-linear relationship (p for non-linearity < 0.001). Figure 2 shows the L-shaped association observed in SEER database cohorts 1–8, with recommended ELNs thresholds as follows: cohort 1 (14), cohort 2 (15), cohort 3 (17), cohort 4 (17), cohort 5 (14), cohort 6 (15), cohort 7 (16), and cohort 8 (15).
Fig. 2.
L-shaped association curves in cohorts 1 through 8 of the Surveillance, Epidemiology, and End Results (SEER) database. Furthermore, the following examined lymph nodes (ELNs) for each cohort are recommended: cohort 1 (ELNs = 14), cohort 2 (ELNs = 15), cohort 3 (ELNs = 17), cohort 4 (ELNs = 17), cohort 5 (ELNs = 14), cohort 6 (ELNs = 15), cohort 7 (ELNs = 16), and cohort 8 (ELNs = 15).
ELNs and overall survival
After adjusting for other prognostic factors, including age, T stage, grade, tumor location, and tumor size, a higher number of ELNs was associated with improved OS in both the SEER database (HR 0.985; 95% CI 0.984–0.986; P < 0.001) and the Chinese cohort (HR 0.977; 95% CI 0.970–0.984; P < 0.001). Patients within each cohort were stratified based on a cohort-specific cut-off value to assess the relationship between the number of ELNs and survival outcomes. This stratification yielded two groups: (1) patients with an ELNs count below the threshold and (2) patients with an ELNs count exceeding or equaling the cut-off. Kaplan–Meier survival curves were then constructed and adjusted for potential confounding factors influencing survival, such as age, tumor size, location, and grade. Across all eight cohorts in the SEER database, patients exceeding the respective ELNs threshold demonstrated a statistically significant survival benefit compared to those falling below the threshold (p < 0.001). Kaplan–Meier curves depicting overall survival for the various ELNs groups within cohorts 1–8 of the SEER database are presented in Fig. 3. Similarly, within the eight cohorts of the Chinese patient population, patients surpassing the cohort-specific minimum ELNs threshold exhibited improved overall survival compared to those falling below the cut-off (Fig. 4).
Fig. 3.
The Kaplan–Meier curves of overall survival for different groups of ELNs in cohort 1-8 from the Surveillance, Epidemiology, and End Results (SEER) database.
Fig. 4.
The Kaplan–Meier curves of overall survival for different groups of ELNs in cohort 1-8 from the Chinese Multi-institutional Registry (CMIR).
Discussion
This study employed two large-scale, independent databases (SEER and CMIR) to investigate the optimal number of examined lymph nodes (ELNs) following hemicolectomy in patients with stage I-III colon cancer (CC), with a total sample size exceeding 130,000. The findings revealed substantial heterogeneity in the minimum ELN thresholds required for optimal survival across different patient cohorts, challenging the current one-size-fits-all recommendation of 12 ELNs in clinical guidelines. By identifying patient-specific factors influencing ELN retrieval and establishing tailored thresholds linked to improved survival, this study provides novel insights for refining postoperative staging and treatment decision-making in CC patients.
Key findings and clinical implications
Our study identified age, tumor size, and tumor location as the most prominent independent predictors of ELN yield, consistent with previous research10,11,13. Older patients (≥ 65 years) tended to have lower ELN counts, which may be attributed to technical challenges during surgery (e.g., decreased tissue resilience and altered anatomical landmarks)10. Larger tumors (≥ 5 cm) were associated with higher ELN retrieval, likely due to the need for more extensive lymph node dissection to ensure adequate clearance of cancerous tissue11,12. Additionally, tumors located in the right colon yielded more ELNs compared to those in the left colon, reflecting anatomical differences in lymphatic drainage patterns and variations in surgical approaches11,13.
A critical finding of this study was that the optimal ELN thresholds for all eight patient cohorts (stratified by age, tumor size, and location) ranged from 14 to 17, exceeding the current CAP guideline recommendation of 12. This aligns with recent studies advocating for higher minimum ELN thresholds to improve survival outcomes10,19. For example, Shetiwy et al.19 demonstrated a significant survival benefit in right colon cancer patients with ≥ 16 ELNs examined. In our study, exceeding the cohort-specific thresholds was associated with significantly improved overall survival (OS) in both the SEER and CMIR databases (all P < 0.001), confirming the clinical value of tailored ELN recommendations. Notably, even in elderly patients with consistently lower ELN yields, the optimal survival threshold remained within the 14–17 range, emphasizing the importance of surgical thoroughness for this population regardless of node quantity retrieved.
Contextualizing ELNs within modern colorectal surgery quality assessment
It is important to acknowledge that ELN count, while historically foundational and guideline-embedded, is a constrained surrogate indicator influenced by technical, anatomical, pathological, and biological factors. Its interpretation outside the context of dissection planes, mesocolic integrity, and lymphadenectomy level (D2/D3) does not fully capture the completeness of surgical resection6,18. In modern colorectal surgery, quality assessment is increasingly shifting toward anatomical and procedural indicators (e.g., complete mesocolic excision, D3 lymphadenectomy) that more directly reflect surgical adequacy14,18. Therefore, the tailored ELN thresholds proposed in this study are intended to complement, not replace, these comprehensive quality metrics.
In resource-limited settings or regions where detailed procedural and anatomical data are not universally available in registries, ELN count remains an accessible and actionable metric for routine clinical practice. Our findings provide a pragmatic solution for optimizing ELN-based staging in such contexts, while acknowledging the synergy between ELNs and modern quality assessment tools. Future guidelines should integrate both tailored ELN thresholds and anatomical/procedural indicators to establish a more holistic framework for evaluating surgical quality in CRC.
Population-level staging patterns and quality improvement
Our dual-database design allowed for the exploration of population-level variations in ELN yield and staging patterns. Geographic differences were observed between the SEER (U.S. population-based) and CMIR (Chinese multi-institutional) datasets: the median ELN count was 16 in SEER and 15 in CMIR, with 71.92% and 72.34% of patients meeting the 12-ELN threshold, respectively. Additionally, modest but statistically significant variations in ELN yield were noted among participating hospitals in the CMIR dataset, reflecting potential differences in surgical practices, pathological processing, or healthcare system organization. These variations highlight the need for standardized surgical and pathological protocols to ensure consistent ELN retrieval across institutions.
For elderly patients, the discrepancy between lower ELN yields and similar survival thresholds suggests that surgical techniques should be optimized to maximize node retrieval in this population, despite inherent technical challenges. Furthermore, the consistency of optimal thresholds across geographic regions (SEER and CMIR) enhances the generalizability of our findings, supporting their potential application in both Western and East Asian clinical settings.
Limitations and future directions
This study has several limitations. First, the retrospective nature of the analysis introduces potential biases in data collection and coding practices. Second, detailed information on surgical techniques (e.g., lymphadenectomy level, mesocolic integrity) and pathological processing methods was not fully captured in the registries, which may have influenced ELN retrieval and interpretation. Third, changes in colon cancer management over the study period (2010–2018) may have led to variations in patient care. Fourth, the generalizability of findings may be limited by differences in healthcare systems and surgical practices between the two datasets.
Future research should address these limitations through prospective studies and randomized controlled trials to validate the tailored ELN thresholds. Additionally, studies integrating detailed surgical and pathological quality indicators (e.g., mesocolic excision status, lymphadenectomy level) with ELN count are needed to establish a more comprehensive quality assessment framework. Further exploration of genetic and molecular factors influencing ELN yield and survival may enable more precise personalization of ELN recommendations14. Cost-effectiveness analyses are also warranted to ensure optimal resource allocation when implementing higher ELN thresholds in clinical practice15,20.
Conclusion
This large-scale, dual-database study demonstrates that the optimal number of examined lymph nodes for colon cancer patients varies by age, tumor size, and location, with thresholds ranging from 14 to 17. These findings challenge the current one-size-fits-all guideline recommendation and support the adoption of tailored ELN thresholds to improve postoperative staging accuracy and long-term survival. While acknowledging the diminishing standalone relevance of ELN count in modern surgical quality assessment, our study highlights its continued value as a pragmatic and accessible metric, particularly when integrated with anatomical and procedural quality indicators. Future guidelines should incorporate these patient-specific thresholds to optimize personalized care for colon cancer patients.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
The authors would like to express their sincere gratitude to doctor Ha Bao Trung Le (tommyle@outlook.com) for his invaluable contributions to this work. Address: 16 Grange Loan, EH9 2NR, Edinburgh, United Kingdom.
Author contributions
B.Y.: Conceptualization, writing. Q.X.: Data curation, statistical analysis. S.J.: Data curation. B.F.: Validation. J.M.: Data collections. R.W.: Data curation.W.Z.: Data curation. J.L.: Data collections. H.L.: Conceptualization. Y.X.: Critical revision of the manuscript for important intellectual content. X.G.: Conceptualization, study design. X.W.: Conceptualization, critical revision of the manuscript for important intellectual content.
Funding
This study was supported by National Key R&D Program for Young Scientists (Grant Number: 2022YFC2505700); Shenzhen Medical Research Fund (C2401010); The National Natural Science Foundation of China (grant number: 82473407).
Data availability
Data were obtained from Chinese multi-institutional registration records (with written informed consent from patients or their guardians) and the SEER database (accessed with authorized permission). All study-generated data are available from the corresponding authors upon reasonable request.
Declarations
Competing interests
The authors declare no competing interests.
Ethical approval
Ethical approval for this study was granted by the Ethics Committee of Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences (Approval number: KY-2024063).Written informed consent was obtained from all patients or their guardians.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Baohong Yang, Qingxia Xu, Shuai Jiao and Boxin Fan contributed equally to this work.
Contributor Information
Haiyi Liu, Email: shanxiliuhaiyi@126.com.
Yanfeng Xi, Email: xiyanfeng1998@163.com.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Data were obtained from Chinese multi-institutional registration records (with written informed consent from patients or their guardians) and the SEER database (accessed with authorized permission). All study-generated data are available from the corresponding authors upon reasonable request.