What is the relationship between cancer and the risk of developing pulmonary embolism (PE)?

From the Guidelines

Cancer significantly increases the risk of developing pulmonary embolism (PE) due to its hypercoagulable state, with certain cancers like pancreatic, lung, brain, and gynecological cancers carrying especially high thrombosis risk. The relationship between cancer and PE is complex, involving multiple factors such as cancer cells releasing procoagulant substances, reduced mobility, and the presence of central venous catheters 1. According to the American Society of Hematology 2021 guidelines, patients with cancer are at greater risk for venous thromboembolism (VTE) compared with the general population, resulting in considerable morbidity, mortality, and costs 1.

The risk of VTE in cancer patients is influenced by various factors, including the type of cancer, treatment, and patient-specific factors 1. For instance, patients receiving chemotherapy have a six-fold increase in the adjusted risk ratio for VTE compared with a healthy population 2. The 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism recommend that patients with cancer should receive indefinite anticoagulation after a first episode of VTE, with the choice between LMWH and edoxaban or rivaroxaban left to the discretion of the physician 3.

Key considerations in managing PE in cancer patients include:

• The high risk of recurrence, which necessitates indefinite anticoagulation 3
• The need for careful assessment of the risk-to-benefit ratio of continued anticoagulant treatment 3
• The importance of patient values and preferences in decision-making 1
• The potential for cancer treatments to increase clotting risk, and the need for prophylactic anticoagulation in high-risk patients 2, 1

Prophylactic anticoagulation with low molecular weight heparin (such as enoxaparin 40mg daily) is often recommended during hospitalization or periods of reduced mobility, and some high-risk patients may require extended prophylaxis even as outpatients. The decision to continue with LMWH or to change to VKA or a NOAC should be made on a case-by-case basis, taking into account the success of anticancer therapy, the estimated risk of recurrence of VTE, the bleeding risk, and the preference of the patient 3.

From the Research

Relationship Between Cancer and Pulmonary Embolism (PE)

• Patients with cancer are prone to develop pulmonary embolism (PE) due to cancer-associated thrombosis, as stated in 4, 5, 6, 7, 8.
• The risk of PE in cancer patients is increased, with a pooled incidence of 3.7% in lung cancer patients, and unsuspected pulmonary embolism (UPE) is also non-negligible, ranging from 29.4% to 63% 6.
• Many risk factors of PE have been detected and could be classified into three categories: lung cancer-related, patient-related, and treatment-related factors 6.
• Decreased mean survival time could be significantly observed in lung cancer patients with PE or UPE compared to those without, and suspected PE has higher mortality than UPE 6.

Treatment and Management of Cancer-Associated PE

• Current first-line treatment in long-term therapy following an episode of PE is low molecular weight heparin (LMWH), with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) listed as viable alternatives 4.
• Thrombolytic therapy should be considered in appropriate patients 5.
• Prophylactic anticoagulant therapy benefit might be highest in patients with stage IV non-small cell lung cancer (NSCLC) or limited small cell lung cancer (SCLC), and heparin seems superior to warfarin for thrombotic prophylaxis 6.
• The brief duration of anticoagulation therapy and elevated likelihood of recurrent VTE serve as cautionary indicators for the need to enhance awareness of standardized anticoagulant treatment for cancer-associated PE 8.

Clinical Characteristics and Outcomes of Cancer-Associated PE

• Pulmonary embolism is the second leading cause of death after the cancer itself in cancer patients, most likely due to difficulties in diagnosing the disease due to its nonclassical presentation 7.
• The risk of PE recurrence and possibly the case-fatality rate depends on whether the patient presents a symptomatic PE, an unsuspected PE, a subsegmental PE, or a catheter-related PE 7.
• Patients with cancer were found to be at a higher risk of recurrent VTE (17.3% vs 4.0%) and all-cause mortality (23.7% vs 10.5%) compared to non-cancer patients 8.