Thanks to advances in both cancer and venous thromboembolism (VTE) management, the epidemiology of cancer-associated thrombosis (CAT) management over time remains unclear. About one out of five VTE events, defined by deep vein thrombosis (DVT) and pulmonary embolism (PE), occurs in patients with cancer. [1]
During the ICTHIC webinar titled “Further insights on the Real-World CAT patient profile from the RIETE Registry,” Professor Laurent Bertoletti delivered a lecture focused on the investigation of temporal trends in clinical characteristics and treatments for CAT based on the analysis of data from the RIETE registry. Here, we summarize the main points from his speech. You can watch Laurent Bertoletti’s lecture in the video below and the full webinar video here.
The RIETE registry
RIETE registry is a prospective, international, ongoing registry of consecutive patients with VTE, launched almost 20 years ago, with more than 100.000 patients currently included and almost 200 active hospitals participating from 29 different countries. All patients with an acute venous clot may participate, except those who are participating in blinded therapy or are unable to be followed up for at least 3 months [2].
In the RIETE registry, baseline characteristics, treatment options, and information on therapeutic management approaches and outcomes during the follow-up period are collected for each patient [2].
The fact that the RIETE registry has been active for several years allows for assessing temporal trends. For example, it has been possible to demonstrate a decrease in 30-day PE-related mortality during the first decade of the century, highlighting how patients’ management has been improved in clinical practice [3]. On the other hand, a growing incidence of CAT has been demonstrated in the last two decades in patients with cancer [4].
Evolution of clinical characteristics
The purpose of the present study is to assess for temporal trends in clinical characteristics and treatments of CAT patients by analyzing all adult patients with objectively confirmed PE or DVT and active cancer. Patients included and followed up in the RIETE registry between 2001 and 2020 were included. The authors also aimed to investigate temporal trends in risk-adjusted rates of VTE recurrences, major bleeding, and death within 30 days from incident VTE [2].
Shedding light on key outcomes and trends observed during the course of the study, Professor Bertoletti has shown how the proportion of patients with CAT, particularly women, has constantly increased. Unexpectedly, the proportion of patients diagnosed with CAT as inpatients (30%) and the average age of CAT patients (67 years) have remained constant all over the 20-year study period, while a slight increase in body weight has been observed [2].
Regarding the clinical presentation of VTE, the authors are surprised to observe, on the one hand, an increase in the proportion of patients diagnosed with PE and, on the other hand, a decrease in the overall proportion of DVT, except for upper-arm DVT [2].
Looking at VTE circumstances and comorbidities, the Professor showed how, in terms of thromboprophylaxis, progress has been made. Indeed, the proportion of patients who develop CAT after surgery or medical immobilization decreased throughout the study period. However, an increase in the prescription of antiplatelets and anti-inflammatory treatments, which may interact with anticoagulant therapy, has been reported [2].
Finally, the proportion of patients with renal impairment has decreased, but it remains a comorbidity to contend with in CAT patients [2].
Evolution of cancer characteristics and therapies
Currently, lung cancer is the most common type of cancer found in patients with CAT. The percentage of patients with lung cancer has increased along with that of breast cancer, while the percentage of men with prostate cancer has decreased. This may be the reason behind the increased percentage of women with CAT. The proportion of patients with colorectal cancer has remained stable [2].
The median time from cancer diagnosis to the occurrence of CAT has remained at 4 months, while an increase in the proportion of patients with metastasis has been proven [2].
Regarding cancer therapies, it has been demonstrated an increased proportion of patients are treated with radiotherapy or chemotherapy and radiotherapy together with immunotherapy. On the opposite, it has been highlighted a huge decrease in the proportion of patients treated with hormonal therapy [2].
How are patients with CAT treated in contemporary times compared to the past?
Regarding the initial therapy of VTE (first week), the proportion of patients treated with low molecular-weight heparin (LMWH) has remained very high throughout the study period, except for the last few years, during which the use of direct-acting oral anticoagulants (DOACs) has increased [2].
The same considerations are also valid beyond the first week of therapy, where a decrease in the proportion of patients treated with vitamin K antagonists (VKA) has been observed [2]. Nowadays, the majority of patients receives LMWH but the proportion of those treated with DOACs increases steadily.
Patients evolution
After analyzing the temporal trends, it was highlighted that there was a decrease in fatal bleeding and fatal PE shortly after the registry was initiated. Moreover, there was also a decrease in overall mortality observed in the second half of the analysis period [2].
According to the professor’s opinion, the most important result is represented by a progressive decline in the 30-day rates of VTE recurrences. Moreover, a constant reduction in the rate of major bleeding has also been demonstrated, except for the last 5 years, during which the rate of major bleeding has been twice as high as the rate of VTE recurrences in CAT patients despite anticoagulant therapy. These results highlight the need to find a way to protect CAT patients from VTE recurrences while simultaneously safeguarding them from anticoagulant-related bleeding [2].
Conclusion
In conclusion, the analysis of data collected in the RIETE registry over the last 20 years has provided various insights into the CAT profile as a patient-modified clinical phenotype and changes in VTE treatments over the years.
Finally, there is a constant reduction in the risk of death, VTE recurrences, and bleeding under anticoagulant therapy. Still, nowadays, the challenge seems to be to reduce the risk of bleeding, which remains at twice the risk of VTE recurrences.
Watch Laurent Bertoletti’s lecture:
References
- Grilz E, Posch F, Nopp S, et al. Relative risk of arterial and venous thromboembolism in persons with cancer vs. persons without cancer-a nationwide analysis. Heart J.2021;42(23):2299–2307, doi: 10.1093/eurheartj/ehab171
- Bertoletti L, Madridano O, Jiménez D, Muriel A, Bikdeli B, Ay C, Trujillo-Santos J, Bosevski M, Sigüenza P, Monreal M, Cancer-Associated Thrombosis: Trends in Clinical Features, Treatment and Outcomes From 2001 to 2020, JACC CardioOncology (2023), doi: https://doi.org/10.1016/j.jaccao.2023.09.003.
- Jiménez D, de Miguel-Díez J, Guijarro R, Trujillo-Santos J, Otero R, Barba R, Muriel A, Meyer G, D Yusen R, Monreal M, Trends in the Management and Outcomes of Acute Pulmonary Embolism: Analysis From the RIETE Registry, J Am Coll Cardiol (2016);67(2):162-170, doi: 10.1016/j.jacc.2015.10.060.
- Mulder FI, Horváth-Puhó E, van Es N, van Laarhoven HWM, Pedersen L, Moik F, Ay C, Büller HR, Sørensen HT, Venous thromboembolism in cancer patients: a population-based cohort study, Blood (2021);137(14):1959-1969, doi: 1182/blood.2020007338