Onco-Cardiology
Incidental Pulmonary Embolism ― How Should We Treat It? ―
2024 年 88 巻 2 号 p. 205-206
詳細
2024 年 88 巻 2 号 p. 205-206
With the development of high-resolution computed tomography (CT), the frequency of incidental, clinically unsuspected pulmonary embolism (PE) is increasing. PE may be discovered incidentally during diagnostic work-up for another disease, especially cancer diagnosis or staging. The clinical status of incidental PE is mostly low risk (non-massive) PE and can be partly submassive PE. Unsuspected incidental PE has been detected in 3.3–5.0% of cancer patients and in 1–2% of all thoracic CT examinations.1–4
Article p 198
Only a few investigations have shown the outcome of untreated patients with isolated subsegmental PE. There are no definitive data comparing treatment results with and without anticoagulation. Stein et al reported there were no episodes of recurrent venous thromboembolism (VTE) in retrospective reports that included in 58 patients, although bleeding occurred in 7–8% of patients with anticoagulation in that review.5 Stein et al suggested that patients with isolated subsegmental PE need not be treated with anticoagulants and recommended clinical observation if the patients are not at high risk.5 The American College of Chest Physicians clinical practice guidelines for antithrombotic therapy for VTE disease suggest the same initial and long-term anticoagulation for incidental PE as for comparable patients with symptomatic PE (Grade 2B) because there are no data demonstrating the safety of withholding anticoagulation.6 In addition, for patients with isolated subsegmental PE, the guidelines suggested clinical surveillance (i.e., a “wait and see” approach) over anticoagulation in patients at low risk of recurrent VTE (Grade 2C), and anticoagulation over clinical surveillance in patients at high risk for recurrent VTE (Grade 2C).6 The definition of “high risk” includes patients with multiple PE, hospitalization, reduced mobility, no reversible risk factors for VTE, and those with a low cardiopulmonary reserve.6 For cancer patients unexpectedly diagnosed with asymptomatic PE, recommended treatment is the same as for comparable patients with symptomatic PE (Grade 1C).7 den Exter et al reported that cancer patients diagnosed with and treated for incidental PE have similar high rates of recurrent VTE, bleeding complications, and mortality as active cancer patients who develop symptomatic PE;8 both groups contain a certain number of cases of isolated subsegmental PE (12% and 17% respectively). Although data on subsegmental PE is limited, the 2019 European Society of Cardiology guideline recommendation is as follows:
In patients with cancer, management of incidental PE in the same manner as symptomatic PE should be considered, if it involves segmental or more proximal branches, multiple subsegmental vessels, or a single subsegmental vessel in association with proven DVT (Class IIa Level B).9
However, the guidelines also stated, “No robust data exist to guide the decision on whether to treat incidental PE with anticoagulants compared with a strategy of watchful waiting”,9 because of poor evidence.
Recently, Kraaijpoel et al reported the results of a large-scale prospective cohort study on the treatment and long-term clinical outcomes of incidental PE in patients with cancer.10 That study demonstrated that isolated subsegmental PE has the same risk of recurrent VTE as patients with more proximal clots, even if most of them are anticoagulated with low molecular weight heparin. Cancer was the most frequent cause of death and bleeding and PE accounted for 3.8% of all deaths.10 The clinical relevance of subsegmental PE remains a matter of debate, because the increased detection of subsegmental clots has not been paralleled by a decrease in PE-related mortality.11 Raslan et al reported that 87% of cases of isolated subsegmental PE were treated and that 42% of patients experienced admission or major bleeding in 3 months, indicating possible overtreatment with anticoagulation.12 The risks of anticoagulation may be greater than the benefits for subsegmental PE, particularly in the Japanese population, which has a higher incidence of bleeding with anticoagulation.
In this issue of the Journal, Nishikawa et al report on a retrospective single-center cohort study of incidental PE among cancer patients in Japan.13 In that study, the incidence of incidental PE was 1.3%, lower than in previous reports. Oral anticoagulants, including direct oral anticoagulants (DOACs), were introduced selectively in 79% of PE patients with careful consideration of the contraindications to anticoagulation and the general condition of the patients, such as palliative care status. Among the PE group of patients, there were no deaths due to PE and none among those receiving anticoagulant therapy. Among the oncology patients, only 4 (2.2%) experienced major bleeding without death. Under a careful anticoagulation policy including subsegmental PE, incidental PE or other thrombosis-related factors did not determine prognosis, although the presence of incidental PE indicated a poorer prognosis due to cancer progression.13 Until definitive results regarding the efficacy of anticoagulation for incidental PE are available, the management policy proposed by Nishikawa et al for incidental PE seems reasonable.
Based on the results reported by Nishikawa et al,13 a tentative policy of using oral anticoagulants, including DOACs, in selected patients with incidental PE, taking into consideration bleeding and cancer status, seems reasonable. Anticoagulation is indicated for proximal and segmental PE. When incidental subsegmental PE is detected, an examination for proximal deep vein thrombosis (DVT) should be performed. If there is proximal DVT, anticoagulation is indicated. Treatment of isolated subsegmental PE depends on the risk of VTE and bleeding (Table).
Cancer-Associated Incidental PE and Treatments
| Type of PE | Treatment |
|---|---|
| Proximal PE | Anticoagulation |
| Segmental PE | Anticoagulation |
| Subsegmental PE with proximal DVT | Anticoagulation |
| Isolated subsegmental PE | Anticoagulation or clinical observationA |
AConsider anticoagulation over clinical observation in case of multiple PE, hospitalization, reduced mobility, no reversible risk factor for venous thromboembolism, and a low cardiopulmonary reserve. Consider clinical observation over anticoagulation in the case of a high risk of bleeding or terminal cancer. DVT, deep vein thrombosis; PE, pulmonary embolism.
The results reported by Nishikawa et al13 also implied that incidental PE can be a part of the expression of the natural history of the disease and indicates substantial cancer progression, as reported previously in studies of asymptomatic DVT and PE.14,15 Incidental PE may be an indicator of cancer progression that cannot be graded by known cancer prognostic factors. Further research into incidental PE is required not only in terms of cancer prognosis, but also with regard to the indications and methods of anticoagulation.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
M.M. has no relationships relevant to the contents of this paper to disclose. Y.Y. has received lecture fees from Daiichi-Sankyo, Bristol-Myers Squibb, Pfizer, and Bayer Healthcare.
