Recurrent VTE in Cancer Still Problematic

Patients with cancer-associated pulmonary embolism (PE) had a significant risk of recurrent venous thromboembolism (VTE) at 12 months, despite anticoagulant therapy, investigators in a large international cohort study reported.

Overall, the 12-month incidence of recurrent VTE was 6.0% and did not differ significantly in patients with subsegmental versus proximal PE. Almost 6% of the 695 patients had major bleeding episodes at 1 year.

Additionally, 43% of the patients died within 12 months, Noemie Kraaijpoel, MD, of the University of Amsterdam, and co-authors reported online in the Journal of Clinical Oncology.

“Results of the current study indicate that patients with cancer with incidental PE have a high risk of recurrent VTE despite anticoagulant treatment, which strengthens current guideline advice to treat incidental PE as symptomatic PE for at least 3 to 6 months,” the authors concluded. “Patients with subsegmental PE seemed to have a risk of VTE recurrence that was comparable with that of patients who had more proximal PE, regardless of the type and dose of anticoagulation, although this subgroup analysis should be considered hypothesis generating.”

“Future intervention studies should validate our findings in patients receiving a standardized treatment regimen and assess whether anticoagulation may be withheld in selected cancer patients with isolated single subsegmental PE who are deemed to have a low risk of recurrent VTE.”

Patients with cancer have a heightened risk of VTE, including deep-vein thrombosis (DVT) and PE, associated with significant morbidity and mortality. About half of all cancer-associated PEs are detected incidentally during imaging for cancer staging, treatment evaluation, or routine follow-up, the authors noted. Prior studies suggested a prevalence of incidental PE in patients with cancer as high as 5%.

Several clinical guidelines recommend anticoagulant treatment for incidentally detected PE in patients with cancer, as well as those with symptomatic PE. However, the treatment recommendations are based primarily on retrospective data and extrapolation of treatment effects from clinical trials of patients with symptomatic PE, the authors continued.

Management of subsegmental PE, in particular, has remained controversial. Results of a systematic review suggested that subsegmental PE may not be clinically relevant in the general population.

The voids in data provided the impetus for an international, multicenter cohort study to assess current treatment strategies for incidental PE in patients with cancer, risk of recurrent VTE, major bleeding, and mortality. Investigators also sought to compare VTE recurrence risk in patients with subsegmental versus more proximal PE.

The study population accrued at 32 centers in Europe and North America, with enrollment from Oct. 22, 2012 to Dec. 31, 2017. Eligible patients had active solid tumors or hematologic malignancies diagnosed or treated within the previous 12 months and incidental PE diagnosis in the 2 months before enrollment. Patients were excluded if they had received any anticoagulant therapy prior to PE diagnosis.

The primary outcomes were recurrent VTE, major bleeding, and all-cause mortality. The 695 patients included in the data analysis had a mean age of 66 and a median Karnofsky performance status of 80%. The most common malignancies were colorectal (21%), lung (15%), and gynecologic (11%) cancers. The authors reported that 44% of the patients had signs or symptoms of PE in the 2 weeks before diagnosis, and 9.1% of PEs were confined to subsegmental arteries.

All but 20 patients (3%) received long-term anticoagulation, continued for a median duration of 216 days. Almost 90% of the patients received low-molecular-weight heparin (LMWH), which was administered at therapeutic doses in 73% of cases.

The data showed that 41 patients had recurrent VTE, which translated into a 12-month cumulative VTE incidence of 6.0%. VTE recurred during treatment in 32 patients, and eight patients died of VTE events. Among the 63 patients with subsegmental VTE, four (6.4%) had recurrent VTE, as compared with 37 of 623 patients with more proximal PE (12-month cumulative incidence 6.0%).

Major bleeding occurred in 39 (5.7% cumulative incidence) patients. The most frequent sites of bleeding were gastrointestinal (21 patients), intracranial (four patients), and urogenital (three patients). Three patients had fatal bleeding incidents.

The authors reported that 283 patients died, representing a 12-month cumulative mortality of 43%. Most deaths resulted from cancer, as PE and bleeding accounted for 3.8% of deaths.

The results were not entirely consistent with data from retrospective studies, some of which included patients with symptomatic and incidentally discovered PE, the authors noted. One such study showed a 12-month cumulative incidence of recurrent VTE of 16.9% for patients with symptomatic PE and 13.3% for incidental PE, although the difference between groups did not reach statistical significance. Additionally, most patients in the multicenter cohort study received LMWH, whereas most patients in retrospective analyses received older regimens associated with a higher risk of recurrent VTE.

The study also did not resolve questions about the clinical relevance of subsegmental PE, the authors continued. Increased detection of the peripherally located clots has not led to a decrease in PE-associated mortality.