ABSTRACT
Background
Pancreatic cancer is associated with a high risk of venous thromboembolism (VTE), with approximately one in five patients developing VTE. Randomized controlled trials have demonstrated that primary thromboprophylaxis is effective and safe in ambulatory patients with pancreatic cancer treated with chemotherapy. Despite international guideline recommendations, thromboprophylaxis appears underused in clinical practice.
Objectives
To assess clinical practice regarding VTE prevention in ambulatory patients with pancreatic cancer among medical oncologists in the Netherlands.
Methods
A nationwide online survey was conducted between March and June 2025 among Dutch medical oncologists involved in pancreatic cancer care. The questionnaire assessed VTE risk perception, use of risk assessment tools, use of thromboprophylaxis, and patient education regarding thrombosis.
Results
Thirty‐eight medical oncologists completed the survey. Most respondents (79%) classified the VTE risk in patients with pancreatic cancer as high or very high, yet 63% never prescribed thromboprophylaxis to ambulatory patients receiving chemotherapy. Lack of a national guideline recommendation was the most frequently reported reason for not prescribing thromboprophylaxis (74%). Only 11% of medical oncologists reported using the Khorana score, and only 3% always discussed VTE risk with patients.
Conclusion
Although medical oncologists recognize the high risk of VTE in patients with pancreatic cancer, thromboprophylaxis remains substantially underused in clinical practice in the Netherlands. Limited awareness of risk assessment tools and national guidance were prominent findings that may inform future implementation efforts. These findings provide a benchmark for assessing the impact of the recently updated Dutch guideline on thromboprophylaxis in this high‐risk population.
Keywords: anticoagulants, pancreas neoplasms, risk assessment, surveys and questionnaires, venous thromboembolism
1. Introduction
Venous thromboembolism (VTE) is a frequent complication in patients with cancer and is associated with morbidity and mortality [1]. Among all malignancies, pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer) carries the highest incidence of thromboembolic disease, with approximately one in five patients developing VTE [2, 3]. The occurrence of VTE is associated with reduced progression‐free survival and overall survival [1, 3].
Although primary thromboprophylaxis is standard practice for hospitalized and surgical patients with cancer, its use remains controversial in the ambulatory setting [4, 5]. Several risk assessment tools have been developed to identify patients at highest risk of VTE, of which the Khorana score is most widely used [6]. As pancreatic cancer itself contributes 2 points to the Khorana score, all patients have a score of at least 2, irrespective of additional clinical or laboratory risk factors, corresponding to at least an intermediate risk of VTE.
Randomized controlled trials demonstrated that thromboprophylaxis with low‐molecular‐weight heparins (LMWH) or direct oral anticoagulants (DOACs) reduces VTE risk by 12.3% to 3.9% in ambulatory patients with pancreatic cancer receiving chemotherapy, without an increase in major bleeding [7, 8, 9, 10, 11, 12, 13]. Consequently, international guidelines of the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN), and International Initiative on Thrombosis and Cancer (ITAC) either suggest or recommend thromboprophylaxis in those with a low risk of bleeding [14, 15, 16, 17]. The ESMO and ASCO guidelines suggest thromboprophylaxis in outpatients with a Khorana score ≥ 2 points treated with chemotherapy [14, 16]. The ITAC and NCCN guidelines specifically recommend starting thromboprophylaxis in patients with locally advanced or metastatic pancreatic cancer, initiating chemotherapy [15, 17].
Although international guidelines provide recommendations, evidence on real‐world implementation is limited, and thromboprophylaxis seems to be underused [4]. The present study evaluated current clinical practice among medical oncologists in the Netherlands and assessed adherence to international guideline recommendations regarding primary thromboprophylaxis in patients with pancreatic cancer.
2. Methods
2.1. Study Design
A cross‐sectional survey was conducted among medical oncologists treating patients with pancreatic cancer in the Netherlands. The questionnaire was developed by a national panel of eight experts in pancreatic cancer‐associated thrombosis and approved by the Dutch Pancreatic Cancer Group [18]. No formal pilot testing, cognitive testing, or validation of the questionnaire was performed prior to distribution. The survey was hosted on Qualtrics. The survey included 18 questions with branching logic and free‐text fields (Table S1).
Medical oncologists involved in pancreatic cancer care were invited via the DPCG and the study committee's network between March and June 2025. An email invitation was sent to 97 oncologists, followed by two reminders. Participation was voluntary and anonymous. Duplicate and incomplete (< 50%) responses were excluded.
2.2. Statistical Analysis
Descriptive statistics were performed to summarize the respondent characteristics and survey outcomes. Categorical variables are presented as frequencies and percentages, and continuous variables as medians with interquartile ranges (IQR). For each survey item, percentages were calculated using the number of respondents who answered or were presented with the respective question as denominator. For multiple‐response questions, each response option was analyzed separately as the proportion of respondents selecting that option. Analyses were performed using SPSS version 28 (IBM CORP., Armonk, NY, USA).
3. Results and Discussion
3.1. Respondent Characteristics
A total of 45 medical oncologists of 97 invited medical oncologists submitted a survey, corresponding to an initial response rate of 46%. Seven surveys were excluded due to less than 50% completion, resulting in a final analytic sample of 38 respondents (39% of those invited). Among the remaining 38 respondents, 42% (n = 16/38) worked in non‐academic tertiary referral centers, 37% (n = 14/38) in academic centers, and 21% (n = 8/38) in non‐academic hospitals. All 38 respondents were medical oncologists, no medical oncologists in training were included. Most respondents (24/37, 65%) had more than 10 years of experience treating pancreatic cancer, followed by 5–10 years (8/37, 22%) and 0–5 years (5/37, 14%), with data missing for one respondent. Regarding annual patient volume, 47% of medical oncologists reported treating 10–30 new patients with pancreatic cancer per year (n = 18/38), 32% treated fewer than 10 (n = 12/38), and 18% treated more than 30 patients (n = 7/38).
3.2. Perceived Risk and Awareness of VTE
When informed that approximately 20% of patients with locally advanced or metastatic pancreatic cancer develop VTE, 12 respondents (12/38, 32%) classified this risk as very high, 18 (18/38, 47%) as high, and seven (7/38, 18%) as moderate. Nevertheless, awareness and use of risk assessment tools were limited: the majority of respondents were not familiar with the Khorana score (n/N = 23/38, 61%), 29% were familiar with the score but did not use it (n/N = 11/38), and 11% used the score (n/N = 4/38).
3.3. Educating Patients on VTE Risk
Discussion of VTE risk with patients occurred infrequently. Only one respondent (1/38, 3%) reported always discussing the risk of VTE, whereas eight (8/38, 21%) discussed this often, 21 (21/38, 55%) sometimes, and eight (8/38, 21%) never. Respondents were asked to indicate for which stages of pancreatic cancer they discussed VTE risk. Most reported discussing VTE risk with patients with metastatic disease (25/38, 66%), followed by locally advanced disease (12/38, 32%), borderline resectable disease (5/38, 13%), and resectable disease (5/38, 13%). Overall, these findings indicate that counseling on VTE risk is inconsistent and tends to occur more often in patients with advanced disease.
Nearly half of the respondents (n/N = 18/38, 47%) reported discussing VTE risk only when patients presented with symptoms suggestive of VTE. Earlier discussions were less common: 10 respondents (10/38, 26%) discussed the risk of VTE at or shortly after diagnosis, nine (9/38, 24%) before initiating chemotherapy, and 15 (15/38, 39%) when imaging results raised uncertainty regarding the presence of VTE. These findings suggest that counseling on VTE risk is often reactive rather than proactively provided in routine patient care.
These findings are consistent with Kaptein et al., who reported that only 4% of Dutch physicians always discussed the risk of cancer‐associated VTE with their patients [19]. Similarly, a European survey among 1365 cancer patients showed that most patients (72%) were unaware of their increased risk of thrombosis, and one quarter first became aware of this risk only after being diagnosed with thrombosis [20]. A global survey among 2262 patients with cancer reported that 55% received no thrombosis education, and 8% only at the time of thrombosis diagnosis, although 79% considered thrombosis awareness highly relevant [21]. Based on these observations, we suggest that structured patient education on the risk, clinical presentation, and potential consequences of cancer‐associated thrombosis should be considered for incorporation into routine care to support awareness and earlier recognition of VTE.
3.4. Perceived Efficacy and Safety of Thromboprophylaxis
Respondents were informed that randomized controlled trials report an estimated number needed to treat (NNT) of 12 for thromboprophylaxis to prevent one VTE in ambulatory patients with locally advanced or metastatic pancreatic cancer receiving chemotherapy [7, 8, 9, 10, 11, 12, 13]. Six respondents (6/38, 16%) considered this NNT high, 22 (22/38, 58%) moderate, nine (9/38, 24%) low, and one (1/38, 3%) very low. The median acceptable NNT for initiating primary thromboprophylaxis as reported by the participating oncologists was 10 (IQR 5–15) (Figure 1).
FIGURE 1.
Perspectives of the respondents on the efficacy and safety of thromboprophylaxis in patients with advanced pancreatic cancer. CVAD, Central venous access device; kg, Kilogram; NNH, Number needed to harm; NNT, Number needed to treat; VTE, Venous thromboembolism.
When presented with an estimated number needed to harm (NNH) of 385 for major bleeding, five respondents (5/38, 13%) classified this NNH as very high, four (4/38, 11%) as high, five (5/38, 13%) as moderate, 15 (15/38, 39%) as low, and nine (9/38, 24%) as very low. This distribution suggests that respondents may have interpreted the NNH categories differently, as a higher NNH reflects a lower risk of harm. Consequently, these findings regarding perceived bleeding risk should be interpreted with caution. Respondents reported that a median NNH of 100 (IQR 50–200) would be too low to justify the use of thromboprophylaxis.
The consistency between trial‐derived estimates and respondents' acceptable NNT and NNH values suggests that factors beyond physician's perceived risk–benefit balance may contribute to the limited use of thromboprophylaxis.
3.5. Use of Thromboprophylaxis in Clinical Practice
Despite recognizing the elevated risk of VTE, 63% of oncologists (n/N = 24/38) reported never prescribing thromboprophylaxis to ambulatory patients with locally advanced or metastatic pancreatic cancer treated with chemotherapy, while 37% (n/N = 14/38) reported prescribing thromboprophylaxis in 1%–24% of cases. In patients with resectable or borderline resectable pancreatic cancer treated with neoadjuvant chemotherapy, 32 respondents (32/38, 84%) never prescribed thromboprophylaxis, and six respondents (6/38, 16%) in 1%–24% of cases. Thus, thromboprophylaxis was infrequently prescribed in both settings, with particularly limited use in patients receiving neoadjuvant treatment for resectable or borderline resectable disease.
The most frequently reported reason for not prescribing thromboprophylaxis was the absence of a recommendation in the Dutch national guideline at the time of the survey (n/N = 28/38, 74%), followed by a perceived low risk of VTE (n/N = 14/38, 37%), lack of evidence for survival benefit (n/N = 13/38, 34%), and perceived low overall VTE burden (n/N = 5/38, 13%) (Figure 2); based on the branching logic, all 38 respondents were presented with this question. These responses suggest that the lack of national guidance, rather than perceived inefficacy or safety concerns, primarily explains the low prescription rates.
FIGURE 2.
Perspectives of respondents on the use of thromboprophylaxis in patients with advanced pancreatic cancer. NNT, Number needed to treat; VTE, Venous thromboembolism.
3.6. Choice of Thromboprophylaxis and Treatment Burden
Among the respondents who prescribed thromboprophylaxis (n = 18), DOACs were the preferred agents (12/18, 67%), followed by LMWH (6/18, 33%). According to the respondents, the treatment burden of thromboprophylaxis is regarded as high, particularly with LMWH, since they see daily subcutaneous injections as a major strain that negatively affects quality of life.
However, evidence on the impact of prophylactic LMWH on quality of life in ambulatory patients with cancer remains limited. In a randomized controlled trial including 2022 patients with lung cancer randomized to LMWH or no LMWH, no significant differences in overall quality of life were observed at 6 and 12 months, as measured by the Hospital Anxiety and Depression Scale and the EuroQol‐5D questionnaire [22]. Similarly, Sideras et al. conducted a randomized trial including 141 patients with advanced cancer, comparing LMWH injections with standard care alone [23]. A 10‐point decrease on the 100‐point Uniscale was observed in 54% of patients receiving LMWH and 51% of those receiving standard care, a difference that was not considered clinically meaningful.
3.7. Estimating Bleeding Risk
When estimating bleeding risk, respondents most frequently considered a prior history of bleeding (n/N = 32/38, 84%), antiplatelet therapy (n/N = 31/38, 82%), liver failure (n/N = 24/38, 63%), and the location of the primary tumor or metastases (n/N = 23/38, 61%) (Figure 1). Randomized trials studying thromboprophylaxis generally excluded patients with a bleeding diathesis, poor performance status, thrombocytopenia, and renal impairment with a creatinine clearance below 30 mL/min [1]. Because the efficacy and safety of thromboprophylaxis remain uncertain for patients with these characteristics, its use should be avoided.
3.8. Discontinuation of Thromboprophylaxis in Patients Nearing the End of Life
When asked about discontinuation of thromboprophylaxis in patients nearing the end of life, 36 of 38 respondents answered the question. Of these, 14 respondents (14/36, 39%) reported they would stop treatment upon transfer to a hospice or palliative care unit, 12 (12/36, 33%) when best supportive care was initiated, and six (6/36, 17%) upon transfer to the general practitioner for best supportive care. Nine respondents (9/36, 25%) indicated they would discontinue thromboprophylaxis when the patient's life expectancy was estimated to be less than three months, and nine (9/36, 25%) when the patient had an ECOG performance status of 4. One respondent (1/36, 3%) indicated they would stop thromboprophylaxis when chemotherapy was discontinued, while one (1/36, 3%) reported to never discontinue thromboprophylaxis.
These responses should be interpreted with caution, as the question was presented to all respondents, including those who did not routinely prescribe thromboprophylaxis, rendering some answers hypothetical. The heterogeneity of responses may nonetheless reflect variability in how clinicians define the end of life, as well as differing views on the potential impact of LMWH on quality of life in this phase and on the impact of acute VTE itself. Importantly, clinical trials informing current evidence typically included treatment durations of up to six months, and it therefore remains uncertain whether the risk–benefit balance of prophylaxis is the same beyond this period [9]. Consequently, the optimal duration of thromboprophylaxis, particularly in patients approaching the end of life, remains unclear, underscoring the need for further research.
3.9. Implications of the New National Guideline
A revised version of the Dutch national guideline on antithrombotic management was published after completion of the survey, in October 2025 [24]. For the first time, this guideline provides recommendations on thromboprophylaxis in patients with malignancies. Specifically, it suggests a DOAC for ambulatory patients with solid malignancies and a high VTE risk (Khorana score ≥ 2), who are starting systemic therapy and have no major risk factors for bleeding. The guideline lists the following bleeding risk factors: diagnosed bleeding disorder, liver dysfunction with coagulopathy, (expected) thrombocytopenia < 50 × 109/L, eGFR < 30 mL/min/1.73 m2, dual antiplatelet therapy, chronic NSAID use, body weight below < 40 kg, and concomitant use of strong CYP3A4 or P‐glycoprotein inhibitors. It further suggests continuing thromboprophylaxis beyond six months, until systemic therapy is discontinued. Thromboprophylaxis should be stopped in the event of clinically relevant bleeding, development of a high bleeding risk, or upon entering the terminal phase.
The guideline also states that the risk of cancer‐associated VTE and the symptoms of VTE should be part of the counseling of patients starting chemotherapy. Shared decision‐making regarding thromboprophylaxis should be explicit: patients should be informed that thromboprophylaxis does not improve survival, and they should be counseled on both its potential to reduce VTE and its associated risk of bleeding.
As pancreatic cancer confers two points in the Khorana score, these recommendations effectively apply to all patients with pancreatic cancer receiving chemotherapy. Our findings indicate that most respondents (90%) were unfamiliar with the Khorana score or did not apply it in practice. Successful implementation of the new guideline will therefore require improved awareness and education among medical oncologists. Future research should evaluate whether these recommendations lead to increased thromboprophylaxis use in the Netherlands.
3.10. Study Limitations
This study has limitations. First, the number of respondents was limited, which did not allow stratified analyses and may limit the generalizability of our findings to all Dutch medical oncologists treating pancreatic cancer. Second, the final response rate of 39% introduces a risk of non‐response bias. Third, participants were recruited through the DPCG and the study committee's professional networks, which may have introduced selection bias. Fourth, participation may have been influenced by personal interest in thromboprophylaxis, introducing self‐selection bias. Fifth, the questionnaire was expert‐developed but not formally validated or pilot tested. Sixth, presenting trial‐derived NNT and NNH values may have influenced respondents' assessment of the benefits and risks of thromboprophylaxis, potentially introducing framing bias. Seventh, prescribing practices were self‐reported and may differ from actual prescribing behavior due to recall or social desirability bias. Finally, differences in healthcare systems and national guidelines may limit the generalizability of our findings beyond the Netherlands. Nonetheless, this survey provides insights into clinical practice and perspectives of clinicians, serving as a benchmark for evaluating future implementation efforts in the Netherlands.
4. Conclusion
Among surveyed Dutch medical oncologists, VTE risk assessment and thromboprophylaxis were infrequently used in ambulatory patients with pancreatic cancer in the Netherlands, despite support by international guidelines. Increased awareness among both clinicians and patients of VTE risk, symptom recognition, and the role of thromboprophylaxis may support improved prevention and management of cancer‐associated thrombosis. Future studies should assess whether implementation of the recently updated Dutch national guideline translates into changes in clinical practice.
Author Contributions
Ruth A. L. Willems: conceptualization, investigation, writing – original draft, methodology, visualization, formal analysis, writing – review and editing, resources, data curation. Merlijn U. J. E. Graus: conceptualization, investigation, writing – original draft, methodology, writing – review and editing, formal analysis, resources, data curation. Eline H. E. van Gansewinkel: resources, writing – review and editing. Aniek E. van Diepen: writing – review and editing. Geert A. Cirkel: supervision, writing – review and editing. Hanneke W. M. van Laarhoven: writing – review and editing, supervision, conceptualization. Miriam L. Wumkes: supervision, writing – review and editing, conceptualization. Marjolein Y. V. Homs: writing – review and editing, supervision, conceptualization, methodology. Johanna W. Wilmink: writing – review and editing, supervision, conceptualization, methodology. F. A. Klok: conceptualization, writing – review and editing, methodology, supervision. Nick van Es: supervision, writing – review and editing, conceptualization, methodology. Hugo ten Cate: writing – review and editing, conceptualization, methodology, supervision. Judith de Vos‐Geelen: conceptualization, writing – original draft, writing – review and editing, supervision, methodology, resources.
Funding
The authors have nothing to report.
Ethics Statement
Ethical approval was not required for this survey among healthcare professionals, as the study did not involve patients or patient data and was not subject to the Dutch Medical Research Involving Human Subjects Act (WMO).
Conflicts of Interest
J.V.‐G. has served as a consultant for Amgen, AstraZeneca, MSD, Pierre Fabre, and Servier, and has received institutional research funding from Servier. All outside the submitted work. H.C. has received institutional fees for consultation and research from Astra Zeneca and Bayer; and for consultation from Alveron, Galapagos, Novostia, and Synapse Research Institute. He is a shareholder with Coagulation Profile, a diagnostic spinoff company from Maastricht University. The other authors declare no conflicts of interest.
Supporting information
Table S1: Survey on thromboprophylaxis in patients with pancreatic cancer.
Acknowledgements
The authors would like to thank the Dutch Pancreatic Cancer Group (DPCG) for their support in distributing the survey within their professional networks.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request via judith.de.vos@mumc.nl.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1: Survey on thromboprophylaxis in patients with pancreatic cancer.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request via judith.de.vos@mumc.nl.