Table 3.

Guideline Recommendations for the Treatment of Cancer-Associated VTE

Guideline	Recommendations
	Initial Treatment	Treatment Duration
ACCPa	Apixaban, edoxaban or rivaroxaban (strong recommendation) Apixaban or LMWH may be preferred in luminal GI malignancies.	Extended-phase DOAC therapy (>3 months) Reassess periodically.
	DOAC (apixaban or rivaroxaban) or LMWH (conditional recommendation) Caution with DOACs in GI cancers.	Treat for 3–6 months with a DOAC (apixaban, edoxaban or rivaroxaban) over LMWH or VKA (conditional recommendations). Treat for >6 months rather than short term (3–6 months) in patients with active cancer (conditional recommendation). Suggest continuing indefinitely rather than stopping after completion of a definitive period of anticoagulation (conditional recommendation). Use a DOAC or LMWH (conditional recommendation).
NCCNa	Apixaban (category 1), edoxaban after ≥5 days of parenteral anticoagulation (category 1) or rivaroxaban (category 2A) preferred for patients without gastric or gastroesophageal lesions Caution in GU tract lesions LMWH preferred for patients with gastric or gastroesophageal lesions (category 1). Dabigatran if above regimens are not appropriate or unavailable.	≥3 months or as long as active cancer or cancer therapy.
ASCOb	LMWH, UFH, fondaparinux, rivaroxaban, or apixaban For long-term anti-coagulation, LMWH, edoxaban, rivaroxaban, or apixaban for at least 6 months are preferred over VKAs. Caution with direct factor Xa inhibitors in patients with GI and GU cancers or other high-risk settings.	Offer LMWH, DOACs or VKAs beyond the initial 6 months to select patients with active cancer, such as those with metastatic disease or those receiving chemotherapy. LMWH, edoxaban or rivaroxaban preferred. LMWH preferred in settings with increased bleeding risk. Assess intermittently to ensure a continued favorable risk-benefit profile. Patients needing extended pharmacologic antithrombotic prophylaxis post cancer surgery Prophylactic doses of LMWH
ESCb	PE and cancer: LMWH for the first 3–6 months (IIa. A) Edoxaban (IIa. B) or rivaroxaban (IIa. C) may be used except in GI cancer patients.	Extend indefinitely or until the cancer is cured (IIa. B). Consider LMWH, DOAC or VKA.
ITACb	LMWH when CrCl ≥30 mL/min (grade 1A). Apixaban or rivaroxaban (first 10 days) or edoxaban (started after initial LMWH/UFH for 5 days) can be used for initial treatment if CrCl ≥30 mL/min and patient is not at high risk of GI or GU bleeding (grade 1 A).	LMWH or DOACs for ≥6 months (grade 1 A) DOACs when CrCl ≥30 mL/min if no impairment in GI absorption or strong DDIs (grade 1 A), but caution advised in GI malignancies, especially upper GI tract. After 6 months, termination or continuation of anticoagulation based on benefit–risk ratio, tolerability, drug availability, patient preference and cancer activity (guidance).
ISTHb	Patients with low bleeding risk and no DDIs: edoxaban or rivaroxaban; LMWHs are acceptable alternatives. Patients with high bleeding riskc: LMWH; edoxaban or rivaroxaban as an alternative if no potential DDI.	No specific recommendation.
NICEb	Consider DOAC if active cancer and confirmed proximal DVT or PE. If DOAC unsuitable, consider LMWH alone or VKA (following initial LMWH). Choice of anticoagulant should consider tumor site, DDIs and bleeding risk.	Review treatment at 3 to 6 months according to clinical need.
ESMO	During the acute phase (first 5–10 days after diagnosis) Consider LMWH, UFH, fondaparinux, apixaban or rivaroxaban (I, A) LMWH is preferable to UFH and fondaparinux (V, A)	For long-term anticoagulation for at least 6 months LMWH, apixaban, edoxaban or rivaroxaban are preferred to VKAs (I, A) In patients with luminal GI cancer, urothelial cancer (II, B), patients at high risk of GI bleeding, receiving powerful inducers and/or inhibitors of CYP3A4 or P-gp, (IV, B) LMWH is preferred. Beyond initial 6 months, LMWH, apixaban, edoxaban, rivaroxaban or VKAs based on benefit–risk assessment (III, B) Regularly assess risk–benefit profile of anticoagulation therapy for favorable balance (IV, C)

Notes: This table collates data from the cited published papers,^{31,37–42,69,72} also over viewed in two previously published studies^55,56 and new data available since then. ^aRecommendations based on ADAM VTE, Caravaggio, Hokusai VTE Cancer and SELECT-D trial results. ^bRecommendations based on Hokusai VTE Cancer and SELECT-D trial results. ^cHigh bleeding risk includes patients with luminal gastrointestinal cancers with an intact primary; cancers at risk of bleeding from the genitourinary tract, bladder, or nephrostomy tubes; or active GI mucosal abnormalities (eg, duodenal ulcers, gastritis, esophagitis, or colitis).

Abbreviations: ACCP, American College of Chest Physicians; ASCO, American Society of Clinical Oncology; CrCl, creatinine clearance; CYP3A4, cytochrome P450 3A4; DDI, drug–drug interaction; DOAC, direct oral anticoagulant; ESC, European Society of Cardiology; ESMO, European Society for Medical Oncology; GI, gastrointestinal; GU, genitourinary; ISTH, International Society on Thrombosis and Haemostasis; ITAC, International Initiative on Thrombosis and Cancer; LMWH, low-molecular-weight heparin; NICE, National Institute for Health and Care Excellence; NCCN, National Comprehensive Cancer Network; P-gp, P-glycoprotein; PE, pulmonary embolism; UFH, unfractionated heparin; VKA, vitamin K antagonist; VTE, venous thromboembolism.