Venous Thromboembolism Prophylaxis and Treatment in Cancer patients: ASCO Guideline Update

Following are the major recommendations:

Clinical Question 1. Should hospitalize patients with cancer receive anticoagulation for VTE prophylaxis?

• Hospitalized patients who have active malignancy and acute medical illness or reduced mobility should be offered pharmacologic thromboprophylaxis in the absence of bleeding or other contraindications (Type: evidence-based; Evidence quality: intermediate; Strength of recommendation: moderate).


• Hospitalized patients who have active malignancy without additional risk factors may be offered pharmacologic thromboprophylaxis in the absence of bleeding or other contraindications (Type: evidence-based; Evidence quality: low; Strength of recommendation: moderate).


• Routine pharmacologic thromboprophylaxis should not be offered to patients admitted for the sole purpose of minor procedures or chemotherapy infusion, nor to patients undergoing stem-cell/bone marrow transplantation (Type: informal consensus; Evidence quality: insufficient; Strength of recommendation: moderate).

Clinical Question 2. Should ambulatory patients with cancer receive anticoagulation for VTE prophylaxis during systemic chemotherapy?

• Routine pharmacologic thromboprophylaxis should not be offered to all outpatients with cancer (Type: evidence-based; Evidence quality: intermediate to high; Strength of recommendation: strong).


• High-risk outpatients with cancer (Khorana score of 2 or higher prior to starting a new systemic chemotherapy regimen) may be offered thromboprophylaxis with apixaban, rivaroxaban, or low-molecular-weight heparin (LMWH) provided there are no significant risk factors for bleeding and no drug interactions. Consideration of such therapy should be accompanied by a discussion with the patient about the relative benefits and harms, drug cost, and duration of prophylaxis in this setting (Type: evidence-based; Evidence quality: intermediate to high for apixaban and rivaroxaban, intermediate for LMWH; Strength of recommendation: moderate).


• Patients with multiple myeloma receiving thalidomide- or lenalidomide-based regimens with chemotherapy and/or dexamethasone should be offered pharmacologic thromboprophylaxis with either aspirin or LMWH for lower-risk patients and LMWH for higher-risk patients (Type: evidence-based; Evidence quality: intermediate; Strength of recommendation: strong).

Clinical Question 3. Should patients with cancer undergoing surgery receive perioperative VTE prophylaxis?

• All patients with malignant disease undergoing major surgical intervention should be offered pharmacologic thromboprophylaxis with either unfractionated heparin (UFH) or LMWH unless contraindicated because of active bleeding, or high bleeding risk, or other contraindications (Type: evidence-based; Evidence quality: high; Strength of recommendation: strong).


• Prophylaxis should be commenced preoperatively (Type: evidence based; Evidence quality: intermediate; Strength of recommendation: moderate).


• Mechanical methods may be added to pharmacologic thromboprophylaxis but should not be used as monotherapy for VTE prevention unless pharmacologic methods are contraindicated because of active bleeding or high bleeding risk (Type: evidence-based; Evidence quality: intermediate; Strength of recommendation: strong).


• A combined regimen of pharmacologic and mechanical prophylaxis may improve efficacy, especially in the highest-risk patients (Type: evidence-based; Evidence quality: intermediate; Strength of recommendation: moderate).


• Pharmacologic thromboprophylaxis for patients undergoing major surgery for cancer should be continued for at least 7 to 10 days. Extended prophylaxis with LMWH for up to 4 weeks postoperatively is recommended for patients undergoing major open or laparoscopic abdominal or pelvic surgery for cancer who have high-risk features, such as restricted mobility, obesity, history of VTE, or with additional risk factors. In lower-risk surgical settings, the decision on the appropriate duration of thromboprophylaxis should be made on a case-by-case basis (Type: evidence-based; Evidence quality: high; Strength of recommendation: moderate to strong).

Clinical Question 4. What is the best method for the treatment of patients with cancer with established VTE to prevent recurrence?

• Initial anticoagulation may involve LMWH, UFH, fondaparinux, or rivaroxaban. For patients initiating treatment with parenteral anticoagulation, LMWH is preferred over UFH for the initial 5 to 10 days of anticoagulation for the patient with cancer with newly diagnosed VTE who does not have severe renal impairment (defined as creatinine clearance less than 30 mL/min) (Type: evidence-based; Evidence quality: high; Strength of recommendation: strong).


• For long-term anticoagulation, LMWH, edoxaban, or rivaroxaban for at least 6 months are preferred because of improved efficacy over vitamin K antagonists (VKAs). VKAs are inferior but may be used if LMWH or direct oral anticoagulants (DOACs) are not accessible. There is an increase in major bleeding risk with DOACs, particularly observed in GI and potentially genitourinary malignancies. Caution with DOACs is also warranted in other settings with high risk for mucosal bleeding. Drug-drug interaction should be checked prior to using a DOAC (Type: evidence-based; Evidence quality: high; Strength of recommendation: strong).


• Anticoagulation with LMWH, DOACs, or VKAs beyond the initial 6 months should be offered to select patients with active cancer, such as those with metastatic disease or those receiving chemotherapy. Anticoagulation beyond 6 months needs to be assessed on an intermittent basis to ensure a continued favorable risk-benefit profile (Type: informal consensus; Evidence quality: low; Strength of recommendation: weak to moderate).


• Based on expert opinion in the absence of randomized trial data, uncertain short-term benefit, and mounting evidence of long-term harm from filters, the insertion of a vena cava filter should not be offered to patients with established or chronic thrombosis (VTE diagnosis more than 4 weeks ago), nor to patients with temporary contraindications to anticoagulant therapy (eg, surgery). There also is no role for filter insertion for primary prevention or prophylaxis of pulmonary embolism (PE) or deep vein thrombosis due to its long-term harm concerns. It may be offered to patients with absolute contraindications to anticoagulant therapy in the acute treatment setting (VTE diagnosis within the past 4 weeks) if the thrombus burden was considered life-threatening. Further research is needed (Type: informal consensus; Evidence quality: low to intermediate; Strength of recommendation: moderate).


• The insertion of a vena cava filter may be offered as an adjunct to anticoagulation in patients with progression of thrombosis (recurrent VTE or extension of existing thrombus) despite optimal anticoagulant therapy. This is based on the panel's expert opinion given the absence of a survival improvement, a limited short-term benefit, but mounting evidence of the long-term increased risk for VTE (Type: informal consensus; Evidence quality: low to intermediate; Strength of recommendation: weak).


• For patients with primary or metastatic CNS malignancies and established VTE, anticoagulation, as described for other patients with cancer, should be offered, although uncertainties remain about the choice of agents and selection of patients most likely to benefit (Type: informal consensus; Quality of evidence: low; Strength of recommendation: moderate).


• Incidental PE and deep vein thrombosis should be treated in the same manner as symptomatic VTE, given their similar clinical outcomes compared with patients with cancer with symptomatic events (Type: informal consensus; Evidence quality: low; Strength of recommendation: moderate).


• Treatment of isolated subsegmental PE or splanchnic or visceral vein thrombi diagnosed incidentally should be offered on a case-by-case basis, considering potential benefits and risks of anticoagulation (Type: informal consensus; Evidence quality: insufficient; Strength of recommendation: moderate).

Clinical Question 5. Should patients with cancer receive anticoagulants in the absence of established VTE to improve survival?

• Anticoagulant use is not recommended to improve survival in patients with cancer without VTE (Type: evidence-based; Evidence quality: high; Strength of recommendation: strong).

Clinical Question 6. What is known about risk prediction and awareness of VTE among patients with cancer?

• There is substantial variation in risk of VTE between individual patients with cancer and cancer settings. Patients with cancer should be assessed for VTE risk initially and periodically thereafter, particularly when starting systemic antineoplastic therapy or at the time of hospitalization. Individual risk factors, including biomarkers or cancer site, do not reliably identify patients with cancer at high risk of VTE. In the ambulatory setting among patients with solid tumors treated with systemic therapy, risk assessment can be conducted based on a validated risk assessment tool (Khorana score; Table 1) (Type: evidence-based; Evidence quality: intermediate; Strength of recommendation: strong).


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  Oncologists and members of the oncology team should educate patients regarding VTE, particularly in settings that increase risk, such as major surgery, hospitalization, and while receiving systemic antineoplastic therapy (Type: informal consensus; Evidence quality: insufficient; Strength of recommendation: strong).