The American Society of Clinical Oncology (ASCO) has been developing guidelines on cancer-associated thrombosis (CAT) since 2007 to aid healthcare professionals in identifying and managing thrombotic events in cancer patients.
While awaiting a full update of the 2019 guidelines, a brief update has been issued, focusing on two of the six clinical questions covered [1]. These questions include Clinical Question 3, which concerns perioperative prophylaxis for venous thromboembolism (VTE) in cancer patients undergoing surgery, and Clinical Question 4, which explores the most effective methods for preventing VTE recurrence in cancer patients with established VTE.
The recent update introduces apixaban as a possible treatment option for VTE in cancer patients. In addition, it incorporates new discoveries on the usage of direct factor-Xa inhibitors for extended thromboprophylaxis after surgery [1].
This article outlines the main points of the newest ASCO Guidelines update on VTE prophylaxis and treatment in patients with cancer.
Should patients with cancer undergoing surgery receive perioperative VTE prophylaxis?
Updated guidelines:
- Prophylactic doses of low-molecular-weight heparin (LMWH) may be offered to candidates for extended pharmacologic thromboprophylaxis after surgery [1].
- As an alternative, prophylactic doses of rivaroxaban or apixaban after an initial period of LMWH or unfractionated heparin may be administered [1].
Previously, direct oral anticoagulants were not recommended for VTE perioperative prophylaxis in patients with cancer due to insufficient evidence.
However, in the last 2 years, two randomized clinical trials have demonstrated the safety and effectiveness of rivaroxaban after laparoscopy for colorectal cancer and apixaban after laparotomy or laparoscopy for gynecological cancer [2,3]. Based on these studies, the revised guidelines now contain a new (weak) recommendation on extended postoperative prophylaxis using apixaban or rivaroxaban, as well as prophylactic dose LMWH, after cancer surgery for patients who may require extended prophylaxis [1].
The two studies varied in design, surgical procedure (laparoscopic or open), type of cancer (colorectal or gynecological), comparator (placebo or LMWH), and primary outcome. More randomized clinical trial data are needed to bolster this recommendation [1].
What is the best method for treatment of patients with cancer with established VTE to prevent recurrence?
Updated guidelines:
- Initial anticoagulation may involve LMWH, UFH, fondaparinux, rivaroxaban, or apixaban. For patients with cancer, newly diagnosed VTE and without severe renal impairment, initiating treatment with parenteral anticoagulation, LMWH is preferred over UFH for the initial 5–10 days of anticoagulation [1].
- Regarding long-term anticoagulation, LMWH, edoxaban, rivaroxaban, or apixaban should be used for at least 6 months, as these options have shown improved efficacy over vitamin K antagonists (VKAs). VKAs may be utilized if the other preferred alternatives are not available. Although direct factor Xa inhibitors decrease recurrent thrombosis, there is an increase in clinically significant non-major bleeding risk when compared to LMWH. Caution is required with direct factor Xa inhibitors, particularly in gastrointestinal and genitourinary malignancies, as well as other scenarios with a high risk of mucosal bleeding. Before utilizing a direct factor Xa inhibitor, it is important to check for potential drug interactions [1].
The efficacy and safety of apixaban for treating cancer-associated thrombosis were not evaluated during the previous guideline revision in 2019 [4]. The recent version, however, examined three randomized clinical studies and concluded that apixaban is now a viable therapy option instead of earlier ones. One of three direct factor-Xa inhibitors, apixaban, differs from rivaroxaban and edoxaban in that it is used twice a day rather than once. There are currently no studies that directly compare the effectiveness of various direct oral anticoagulants in this clinical setting [1].
Full set of ASCO perioperative recommendations
Here, we summarize all the ASCO Guidelines recommendations concerning perioperative prophylaxis for VTE in cancer patients undergoing surgery and the most effective methods for preventing VTE recurrence in cancer patients with established VTE, inclusive of the recent updates [1].
Perioperative VTE prophylaxis in patients with cancer undergoing surgery [1]
- Unless precluded by active bleeding, a high risk of bleeding, or other contraindications, pharmacologic thromboprophylaxis with either UFH or LMWH should be made available to all patients with malignant illness requiring significant surgical intervention.
- Prophylaxis with UFH or LMWH should be commenced preoperatively.
- If pharmaceutical thromboprophylaxis is contraindicated due to active bleeding or a high risk of bleeding, mechanical methods may be supplemented, but they should not be utilized as a stand-alone treatment for VTE prevention.
- Particularly in the highest-risk patients, a combined regimen of pharmacological and mechanical prophylaxis may increase effectiveness.
- Pharmacologic thromboprophylaxis for patients undergoing major surgery for cancer should be continued for at least 7–10 days.
- Patients undergoing major open or laparoscopic abdominal or pelvic surgery for cancer who have high-risk characteristics, such as restricted mobility, obesity, a history of VTE, or with other risk factors, should be administered extended pharmacologic thromboprophylaxis for up to 4 weeks postoperatively. The choice of the proper length of thromboprophylaxis in lower-risk surgical situations should be determined on a case-by-case basis.
- Prophylactic doses of LMWH may be offered to candidates for extended pharmacologic thromboprophylaxis after surgery (updated guideline).
- As an alternative, prophylactic doses of rivaroxaban or apixaban after an initial period of LMWH or unfractionated heparin may be administered.
Best treatment methods to prevent recurrence in patients with cancer with established VTE [1]
- Initial anticoagulation may involve LMWH, UFH, fondaparinux, rivaroxaban, or apixaban. For patients with cancer, newly diagnosed VTE and without severe renal impairment, initiating treatment with parenteral anticoagulation, LMWH is preferred over UFH for the initial 5–10 days of anticoagulation (updated guideline).
- Regarding long-term anticoagulation, LMWH, edoxaban, rivaroxaban, or apixaban should be used for at least 6 months, as these options have shown improved efficacy over vitamin K antagonists (VKAs). VKAs may be utilized if the other preferred alternatives are not available. Although direct factor Xa inhibitors decrease recurrent thrombosis, there is an increase in clinically significant non-major bleeding risk when compared to LMWH. Caution is required with direct factor Xa inhibitors, particularly in gastrointestinal and genitourinary malignancies, as well as other scenarios with a high risk of mucosal bleeding. Before utilizing a direct factor Xa inhibitor, it is important to check for potential drug interactions (updated guideline).
- Selected individuals with active cancer, such as those with metastatic illness or those taking chemotherapy, should be administered anticoagulation with LMWH, direct factor Xa inhibitors, or VKAs after the first six months. To maintain a good risk–benefit profile, anticoagulation beyond 6 months needs to be periodically evaluated.
- Given the lack of randomized trial data, uncertain short-term benefits, and increasing evidence of long-term harm from filters, it is not advisable to offer vena cava filter insertion to patients with established or chronic thrombosis (diagnosed more than 4 weeks ago) or to those with temporary contraindications to anticoagulant therapy, such as those undergoing surgery. Vena cava filters should also not be used for primary prevention or prophylaxis of PE or DVT due to concerns about long-term harm. However, in cases where patients have absolute contraindications to anticoagulant therapy and the thrombus burden is life-threatening, vena cava filter insertion may be considered in the acute treatment setting (diagnosis within the past 4 weeks). It is essential to conduct further research on this topic.
- In patients who continue to develop thrombosis (recurrent VTE or extension of an existing thrombus) after receiving the best anticoagulant medication, the implantation of a vena cava filter may be suggested as an adjuvant to anticoagulation. Given the lack of a survival improvement, the minimal short-term benefit, and accumulating evidence of the long-term elevated risk for VTE, this is based on the panel’s expert view.
- Anticoagulation as outlined for other cancer patients should be made available to patients with primary or metastatic central nervous system malignancies and established VTE, while there are still questions about the best drugs to use and who will benefit from it.
- Given their similar clinical outcomes compared to individuals with cancer who experience symptomatic episodes, incidental PE and DVT should be treated in the same way as symptomatic VTE.
Treatment for isolated subsegmental PE or incidentally discovered splanchnic or visceral vein thrombi should be provided case-by-case while taking into account the potential advantages and dangers of anticoagulation.
References
- Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO guideline update. J Clin Oncol. 2023. doi:10.1200/JCO.23.00294. Epub ahead of print.
- Becattini C, Pace U, Pirozzi F, et al. Rivaroxaban vs placebo for extended antithrombotic prophylaxis after laparoscopic surgery for colorectal cancer. Blood. 2022;140(8):900-908. doi:10.1182/blood.2022015796
- Guntupalli SR, Brennecke A, Behbakht K, et al. Safety and efficacy of apixaban vs enoxaparin for preventing postoperative venous thromboembolism in women undergoing surgery for gynecologic malignant neoplasm: a randomized clinical trial. JAMA Netw Open. 2020;3(6):e207410. doi:10.1001/jamanetworkopen.2020.7410
- Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2020;38(5):496-520. doi:10.1200/JCO.19.01461