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. 2025 Aug 8;58(8):1109–1119. doi: 10.1007/s11239-025-03164-5

Postoperative venous thromboembolism risk following lung cancer surgery: a systematic review and meta-analysis

Jing Chen 1,2,3, Yuanzheng Mao 1,2,3, Zhiyu Peng 4,✉
PMCID: PMC12740955  PMID: 40779190

Abstract

Venous thromboembolism (VTE) remains a major contributor to postoperative morbidity and mortality in patients undergoing lung cancer surgery. This study aims to identify perioperative risk factors associated with VTE development following such procedures. We performed an exhaustive search of PUBMED and EMBASE from inception to November 1, 2023, using terms related to VTE following lung cancer surgery. A random-effects meta-analysis was performed to calculate the pooled incidence and odds ratios (ORs) for risk factors. Of 3,576 screened studies, 13 met eligibility criteria for qualitative synthesis, and 11 studies (53,382 patients) were included in the meta-analysis. The pooled incidence of postoperative VTE was 1.82% (971 cases). Significant risk factors included advanced age (standardized mean difference [SMD] 0.43, 95% CI 0.22–0.63; I2 = 59.9%), prolonged surgical duration (SMD 0.58, 95% CI 0.24–0.92; I2 = 81.2%), open thoracotomy (OR 1.77, 95% CI 1.50–2.09; I2 = 19.9%), TNM stage > 1 (OR = 1.81, 95% CI 1.53–2.13; I2 = 39.8%), adenocarcinoma histology (OR = 1.29, 95% CI 1.08–1.53; I2 = 1.2%), and major lung resection (OR = 1.51, 95% CI 1.24–1.83; I2 = 0.0%). This study highlights key modifiable and non-modifiable risk factors for postoperative VTE in lung cancer surgery patients. These findings support individualized risk stratification and targeted thromboprophylaxis strategies to improve clinical outcomes.

Supplementary Information

The online version contains supplementary material available at 10.1007/s11239-025-03164-5.

Introduction

Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), significantly elevates morbidity and mortality in patients undergoing lung cancer surgery [1]. Despite advances in minimally invasive techniques and perioperative prophylaxis, VTE incidence remains substantial (4–14%) in this population [2, 3].

Tumors and surgery are recognized risk factors for the development of VTE [4]. Patients with tumors following surgery for lung cancer are more susceptible to VTE due to a potentially prothrombotic state [5]. Chest drainage and pain after lung cancer surgery reduces patient activity and increases risk of VTE [6]. Although prior studies have explored the risk factors for VTE after lung cancer surgery, these studies have been conducted across different surgical centers and patient populations, leading to variability in findings. Although certain studies have proposed predictive models for determining whether patients are at high risk of VTE, the reported risk factors differ across studies, and no universally accepted or widely implemented model has been established [7–10].

Considering the clinical significance of VTE, improving the identification and prediction of its risk factors is essential for optimizing preoperative assessment and formulating individualized prevention and management strategies. However, studies conducted in different populations and geographic regions exhibit substantial heterogeneity, not only in baseline patient characteristics and surgical techniques but also in sample size and study design. While previous reviews have examined VTE risk factors in the context of oncologic surgery [11, 12], but there are no meta-analyses or systematic reviews of the risk variables for VTE in patients having surgery for lung cancer. Through a comprehensive review and meta-analysis of the literature, this study aimed to determine the major risk variables associated with VTE.

Methods

Data sources, searches, and selection criteria

This review was pre-registered with PROSPERO (ID: CRD42023482068) prior to data extraction and conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic review and meta-analysis reporting [13].

A comprehensive electronic literature search was carried out in PubMed and Embase by two independent authors (J.C. and J.L.) from inception to November 28, 2023. The search strategy utilized three groups of keywords: (1) “venous thromboembolism,” “deep vein thrombosis,” and “pulmonary embolism”; (2) “lung cancer,” “lung carcinoma,” and “lung neoplasm”; and (3) “surgery,” “operation,” and “surgical intervention.” The complete search strategy for each database is detailed in the supplementary material (Table S1). Additionally, the reference lists of relevant studies were manually screened to identify additional eligible studies. The follow-up period in these studies was restricted to no more than three months. Only randomized trials and observational studies were included, whereas in vitro research, animal research, case reports, and case series were excluded.

Data extraction and quality assessment

Studies that examined risk factors for VTE in patients having pulmonary oncologic resection and were published in English were considered for inclusion. Extracted data from eligible studies included the first author, publication year, study design, study period, total number of patients, number of patients with VTE, follow-up duration, and key study limitations. Only outcome measures reported in at least two studies incorporated into the meta-analysis. These outcome measures comprised patient age, sex, BMI, comorbidities, history of preoperative adjuvant therapy, smoking history, surgical duration, surgical approach, tumor-node-metastasis (TNM) stage, histological subtype of the lung tumor, and surgical approach. Quality assessment was performed using the Newcastle-Ottawa Scale (Table S2) [14]. Two reviewers (J.C. & J.L.) independently carried out the data extraction and quality evaluation, with a third reviewer (ZY.P.) resolving any disputes.

Statistical analysis

Odds ratios (ORs) with 95% confidence intervals (CIs) were computed to provide a summary of each possible risk factor’s impact on VTE in patients undergoing pulmonary oncologic resection. Forest plots were generated to visualize the ORs from individual studies alongside the pooled OR. Given the expectation of substantial between-study variability, random-effects models were used to prespecify all meta-analyses The heterogeneity was assessed using the Cochrane Q test, and the I2 statistic was used to quantify it. Heterogeneity was deemed statistically significant when I² ≥ 50% or P ≤ 0.05. Sensitivity analyses were performed by progressively eliminating each study and reanalyzing the remaining data in order to evaluate the findings’ robustness. Publication bias was examined using Egger’s test to assess the correlation between effect estimates and their variances. Any statistical test was considered statistically significant if the P-value was less than 0.05. Every analysis was performed using Stata software (version 17.0).

Results

Study characteristics

The initial literature search yielded 3,576 studies. After applying the predefined inclusion and exclusion criteria, the systematic review comprised 13 studies [7–10, 15–23], and the meta-analysis had 11 papers [7–10, 15, 17–22] (Fig. 1). Patient inclusion periods for the included research ranged from 1990 to 2022, and they were all retrospective observational studies (Table 1). Most studies reported VTE—including both DVT and PE—as the primary outcome. However, two studies specifically focused on PE as the sole outcome measure [9, 10]. The included studies have a broad range of sample sizes, ranging from 157 to 14,308 patients, with reported VTE incidence rates between 1.1% and 20%. Two studies restricted their study populations based on the extent of resection, including only patients who underwent lobectomy or pneumonectomy [8, 21]. Additionally, three studies focused exclusively on patients with stage I tumors according to the TNM classification [16, 18, 23].

Fig. 1.

Fig. 1

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Flow diagram showing search strategy and study selection

Table 1.

Characteristics of included studies that assessed risk factors for VTE

Author Year Country Study design Study period VTE type No. of participants No. of VTE events within 3 months after surgery Follow-up time Notable limitations
Mørkved 2023 Denmark Retrospective observational 2003–2021 VTE (PE, DVT) 13,197 145 Three months, one year No
Ding 2023 China Retrospective observational 2019.10-2021.3 VTE (PE, DVT) 601 63 Post-operative hospitalization No
Cai 2023 China Retrospective observational 2017.1-2022.1 VTE (PE, DVT) 452 40 Post-operative hospitalization Not enough data for meta-analysis
Zhang 2022 China Retrospective observational 2010.5-2018.8 VTE 952 100 Two to three years Not enough data for meta-analysis
Ke 2022 China Retrospective observational 2016.8-2019.12 VTE (PE, DVT) 1,205 87 One month No
Dong 2022 China Retrospective observational 2017.1-2021.7 VTE 314 23 Post-operative hospitalization No
Akhtar-Danesh 2022 Canada Retrospective observational 2007–2017 VTE 12,626 166 Three months, one year No
Li 2021 China Retrospective observational 2015.1-2018.7 PE 680 136 Post-operative hospitalization No
Thomas 2018 USA Retrospective observational 2005–2015 VTE (PE, DVT) 14,308 234 One month No
Li 2018 China Retrospective observational 2012.1-2015.7 PE 9,726 61 One month No
Hachey 2016 USA Retrospective observational 2005–2013 VTE (PE, DVT) 232 12 Two months No
Agzarian 2016 Canada Retrospective observational 2013.6-2014.12 VTE (PE, DVT) 157 19 One month No
Mason 2006 USA Retrospective observational 1990.1-2001.1 VTE 336 25 Post-operative hospitalization No
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VTE, venous thromboembolism; PE, pulmonary embolism; DVT, deep vein thrombosis

Risk factor analysis for VTE

Table 2 presents the mean differences, pooled ORs or SMDs, 95% CIs, and heterogeneity metrics obtained from meta-analyses with fixed or random effects. Table S3 compiles the significance of risk factors at the specific research level depending on univariate and multivariable analyses. Forest plots, such as Fig. 2 for major lung resection, and funnel plots, such as Fig. 3 for major lung resection, are included individually in the supplemental materials for every risk factor. The findings of Egger’s test were not significant in any of the funnel plots. and visual assessment indicated sufficient symmetry among the included studies.

Table 2.

Meta-analysis of preoperative and intraoperative risk factors for VTE

Risk factor No. of studies Patients with factor/ total Random/ fixed effects pooled OR or SMD (95% CI) P P for heterogeneity chi-squared I2 (%)
With VTE No VTE
Increased age 6 334 12,002 SMD: 0.43 (0.22, 0.63) < 0.001 0.029 59.9
Male sex 11 508/965 25,540/51,782 OR: 1.14 (0.90, 1.44) 0.290 0.005 60.7
Increased BMI 4 260 2193 SMD: 0.23 (-0.09, 0.55) 0.165 0.003 78.0
Hypertension 6 329/681 16,316/28,798 OR: 1.12 (0.95, 1.32) 0.167 0.556 0.0
Diabetes 6 106/643 5165/28,725 OR: 1.02 (0.70, 1.49) 0.910 0.091 47.4
COPD 2 146/400 9339/26,534 OR: 1.07 (0.43, 2.68) 0.887 < 0.001 94.9
History of other tumors 2 14/206 81/1761 OR: 1.19 (0.67, 2.13) 0.553 0.570 0.0
History of bone fracture or surgery 2 5/223 49/1662 OR: 1.02 (0.39, 2.64) 0.969 0.692 0.0
Preoperative adjuvant therapy 4 26/390 422/13,866 OR: 1.36 (0.58, 3.18) 0.478 0.035 65.1
Smoking history 4 135/417 5708/16,021 OR: 0.90 (0.73, 1.11) 0.306 0.263 24.7
Increased surgical duration 2 223 1662 SMD: 0.58 (0.24, 0.92) 0.001 0.021 81.2
Increased preoperative PLT 2 159 835 SMD: -0.13 (-0.75, 0.50) 0.688 0.007 86.2
Open thoracotomy 9 366/795 17,335/39,047 OR: 1.77 (1.50, 2.09) < 0.001 0.266 19.9
TNM stage > I 8 316/679 14,575/37,725 OR: 1.81 (1.53, 2.13) < 0.001 0.114 39.8
Adenocarcinoma 10 423/727 20,599/38,161 OR: 1.29 (1.08, 1.53) 0.003 0.427 1.2
Major lung resection 8 549/699 27,765/37,621 OR: 1.51 (1.24, 1.83) < 0.001 0.772 0.0
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VTE, venous thromboembolism; BMI, body mass index; COPD, chronic obstructive pulmonary disease; PLT, platelet; TNM, tumor node metastasis

Fig. 2.

Fig. 2

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Forest plot for meta-analysis of the association of open thoracotomy and VTE

Fig. 3.

Fig. 3

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Funnel plot to detect publication bias for open thoracotomy, Egger test, P = 0.27

Systematic review and meta-analysis: individual risk factor results

Increased age

The relationship between age and VTE, either as a continuous or categorical variable, was investigated in thirteen research. Six studies pooled age as a continuous variable, yielding a significant SMD = 0.43 (95% CI, 0.22–0.63), with moderate heterogeneity and an overall low quality of evidence.

Increased surgical duration

Seven studies evaluated the relationship between surgical duration (analyzed as either a continuous or categorical variable) and VTE. Pooled data from two studies treating surgical duration as a continuous variable showed a significant MD = 0.58 (95% CI, 0.24–0.92), with high heterogeneity and an overall low quality of evidence.

Open thoracotomy

Eleven studies investigated the association between open thoracotomy and VTE. Pooled data from nine studies demonstrated a noteworthy association (OR = 1.77, 95% CI 1.50–2.09) with low heterogeneity, but the evidence’s overall quality remained poor.

TNM stage II-IV

Ten studies examined the association between TNM stage II-IV and VTE. Pooled data from eight studies did not indicate a statistically noteworthy association (OR = 1.81, 95% CI 1.53–2.13), with low heterogeneity and generally poor evidence quality.

Adenocarcinoma

Ten studies assessed the association between adenocarcinoma and VTE. The pooled results demonstrated a significant association (OR = 1.29, 95% CI 1.08–1.53), with poor quality of evidence overall and low heterogeneity.

Major lung resection

Eleven research looked into how massive lung resection affected the risk of VTE. Pooled data from eight studies revealed a significant association (OR = 1.51, 95% CI 1.24–1.83), with poor quality of evidence overall and low heterogeneity.

Other risk factors studied only qualitatively

Table S3 summarizes the importance of lower preoperative FEV1, FVC, MCC, DLCO, and increased preoperative D-dimer levels as potential predictors of VTE.

Other risk factors requiring further study

The meta-analysis omitted several risk factors because they were only determined to be significant in one research. Factors that were previously found to be important in univariate analysis: ASA score > 2, increased preoperative Hgb, FDP, NSE, and CA153.

Risk factors where multiple studies have never shown association

The systematic review did not include qualitative or quantitative analyses of many additional factors that have shown a nonsignificant link with VTE: pleural adhesion, CCI ≥ 2, Solidity nodule morphology, FEV1/FVC < 70%.

Discussion

This systematic review and meta-analysis aimed to identify and synthesize previously proposed risk factors for VTE following lung cancer surgery. A total of 35 distinct risk factors were examined in the systematic review, of which 16 were quantitatively assessed through meta-analysis. The findings provide sufficient evidence confirming the following elements as important risk factors for VTE following surgery: advanced age, prolonged surgical duration, major anatomic lung resection, open thoracotomy, and higher TNM stage. Despite the fact that the majority of risk variables have evidence quality ratings of low or very poor—indicating that the estimated effect sizes may deviate from the true associations—this review offers a thorough summary of recent findings. By consolidating findings on all potential risk factors, it offers valuable insights that can inform future studies and guide further investigation into VTE risk stratification and prevention in individuals having surgery for lung cancer.

Previous studies have demonstrated that although the bulk of VTE incidents take place in the first month following surgery, a subset of cases manifest within the subsequent two months [24, 25]. In oncologic surgery, the relative risk of VTE significantly declines beyond the three-month postoperative period. Consequently, the included studies’ follow-up periods were restricted to three months in this study. VTE risk factors can be roughly divided into three categories: preoperative, intraoperative, and postoperative factors. Preoperative factors primarily pertain to the patient’s baseline physiological status, whereas surgical methods have a greater direct impact on intraoperative and postoperative measures and procedural characteristics. Gaining an understanding of preoperative and intraoperative risk factors is crucial for maximizing preoperative patient counseling and implementing targeted VTE prevention strategies. However, several risk factors, including advanced age and declining pulmonary function, are non-modifiable, others remain modifiable. These consist of perioperative dietary optimization, preoperative smoking cessation, and perioperative nutritional optimization. Investigating these modifiable factors can assist in identifying high-risk individuals and inform the development of perioperative anticoagulation prophylaxis protocols, ultimately improving patient outcomes.

It is commonly known that individuals with benign illnesses are less likely to have VTE than those undergoing cancer surgery [26]. Among patients with malignant tumors, both disease stage and histological subtype are key determinants of VTE risk [27]. The procoagulant state associated with malignancy arises from complex interactions between tumor cells and the hemostatic system. Tumor cells can invade blood vessels, expose plasma to tumor-derived procoagulants such as tissue factor, and subsequently activate the coagulation cascade [28]. In this study, VTE risk was substantially correlated with illness stage, with patients diagnosed at stage II or higher exhibiting an almost twofold increase in VTE incidence compared to those with stage I disease. Similarly, tumor histology was identified as a contributing factor, with an increased incidence of VTE over the 90 days following surgery being linked to adenocarcinoma. However, care should be used when interpreting this finding, as the relatively low number of VTE events observed within the selected follow-up window may limit the clinical significance of this association.

Furthermore, the extent of pulmonary resection, the degree of surgical trauma, and the duration of the procedure were all shown to be important indicators of the likelihood of postoperative VTE. Pneumonectomy was linked to a higher incidence of postoperative VTE, according to Kim et al. [29]. Patients undergoing pneumonectomy exhibit elevated levels of circulating coagulation factors, which may contribute to their heightened risk of VTE [30]. Additionally, open thoracic surgery is linked to a greater incidence of VTE than VATS, according to many studies. The findings of the present meta-analysis align with these observations, indicating that decreased postoperative inflammation may be the cause of the lower VTE risk linked to VATS, decreased pain levels, shorter chest tube retention time, and improved postoperative mobility [15]. We believe that for all patients undergoing major surgeries or open thoracic surgeries, prophylaxis of venous thrombosis is essential. For this group of patients, if there is no risk of bleeding after assessment, anticoagulant medication should be initiated as soon as possible.

Obese persons are more likely to develop deep vein thrombosis and pulmonary embolism, according to many studies, whereas being underweight seems to provide a decreased risk of VTE [10, 31, 32]. However, the meta-analysis of the four studies that made up this study revealed no proof that there is a substantial relationship between postoperative VTE risk and elevated BMI (SMD 0.23, 95% CI -0.09–0.55). This discrepancy may result from the limited sample size and the treatment of BMI as a continuous variable in the included studies. Further large-scale studies are warranted to elucidate this relationship more definitively.

Chemotherapy and radiation are also thought to increase the risk of VTE [33, 34]. A change from an anticoagulant to a procoagulant condition may result from damage to the vascular endothelium caused by radiation or chemotherapy [35]. However, the meta-analysis of four studies in this research failed to find a correlation that was statistically significant between chemotherapy or radiotherapy and VTE risk in patients with NSCLC (OR = 1.36, 95% CI 0.58–3.18). These results might be attributed to the limited number of patients receiving neoadjuvant chemotherapy or radiotherapy. Notably, most prior studies reporting an elevated risk of VTE associated with chemotherapy and radiotherapy focused on overall VTE incidence rather than specifically on postoperative VTE. In studies exclusively examining postoperative VTE, the association with radiotherapy remains unclear and warrants further investigation.

VTE is linked to worsened postoperative morbidity, extended hospital stays, and higher healthcare costs, with PE being the main reason why individuals who have cancer surgery die after surgery [36]. Previous studies, which included patients who underwent surgery for nine different types of malignancies, discovered that the greatest fatality rate linked to VTE episodes was reported in individuals with lung cancer [29]. Current recommendations for preventing VTE following lung surgery are not supported by actual evidence but rather by extrapolated data, despite the fact that patients with lung cancer are among those most at risk for postoperative VTE [37]. Previous study indicates that the risk of VTE is highest in the first three months following surgery, a pattern consistent with an increased postoperative inflammatory state [15]. However, most lung cancer patients are discharged within a few days following surgery, and there are currently limited recommendations for VTE prophylaxis after discharge. Given the substantial incidence of postoperative VTE in this population, greater consideration should be given to strategies for reducing VTE risk during the postoperative period, including extended thromboprophylaxis and routine screening.

This study has a number of drawbacks that should be noted despite its positives. First, the retrospective nature of all the included papers in this systematic review naturally raises the possibility of publication bias. In meta-analyses, studies are often excluded due to inconsistencies in variable definitions or reporting formats, potentially introducing additional bias. This study excluded non-English studies, which might also contribute to the occurrence of publication bias. Furthermore, certain risk factors assessed in only a single study could not be systematically analyzed, highlighting the need for further investigation. Additionally, for the combined estimates, unadjusted effect sizes were used, preventing the identification of independent predictors of VTE. Moreover, many studies lacked standardized diagnostic criteria for VTE or did not report whether VTE was actively monitored, increasing the likelihood of misclassification and underestimation of VTE incidence. Since all the studies included in this research are retrospective and the results are observational, future studies need to be prospective and large-scale to conduct further analysis of various factors. Finally, the majority of the studies included in this research originated from the United States and China. Such geographical biases could also potentially lead to the occurrence of bias. Future research should address these limitations by incorporating prospective study designs, standardized outcome definitions, and systematic screening protocols to improve the accuracy and reliability of VTE risk assessment in lung cancer surgery patients.

Conclusion

The first systematic review and meta-analysis of risk variables for VTE after lung cancer surgery is presented in this work. Our findings indicate that increased age, prolonged surgical duration, open thoracotomy, TNM stage > I, adenocarcinoma, and substantial lung resection are important risk factors for VTE following surgery. These results provide valuable insights into patient risk stratification and emphasize the necessity of additional study to develop a condensed collection of independent predictors that may be extensively used in clinical settings. The formulation and execution of evidence-based, targeted clinical care pathways for VTE prevention could improve patient outcomes and optimize perioperative management strategies in lung cancer surgery.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1 (8.4MB, docx)
Supplementary Material 2 (98.6KB, pdf)

Acknowledgements

We sincerely thank the authors of studies included in these reviews for providing additional data, which contributed to the completeness of our analysis. The corresponding author had complete access to all data in this study and assumes responsibility for its integrity and the accuracy of the data analysis.

Author contributions

Dear Editor-in-Chief, In this manuscript, the contributions of the authors are as follows: Jing Chen contributed to data management, conceptualization, formal analysis, and writing; Zhiyu Peng contributed to supervision, validation, review, and editing; Yuanzheng Mao contributed to investigation, methodology, project management, and resources.Thank you.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary Material 1 (8.4MB, docx)
Supplementary Material 2 (98.6KB, pdf)

Data Availability Statement

No datasets were generated or analysed during the current study.

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