Venous Thromboembolism and Bleeding Risk in Bladder Cancer

Venous thromboembolism ([VTE] including deep venous thrombosis [DVT] and pulmonary emboli [PE]) occurs with an annual incidence of 160 per 100,000 within the general population in North America, and DVT and PE carry an annual economic burden of $33,000 and $3,200, respectively, per patient.[1,2] While VTE events are uncommon in the general population, the risk of developing a VTE rises substantially with an increase in the number of operative procedures, patient age, and medical comorbidities, and is exacerbated in patients with cancer.

To reduce the risk of VTE, thromboprophylactic measures in the form of chemical anticoagulation (heparin, low-molecular-weight heparin [LMWH]), mechanical prophylaxis (compression stockings, sequential compression devices), and early postoperative mobilization have been implemented in clinical practice. Despite these management approaches, there is little consensus regarding the optimal regimen for, and duration of, pre- and postoperative therapies.[3] Furthermore, many US-based hospitals do not have a standing policy regarding prophylaxis to reduce the risk of postoperative VTEs.[4] A recent prospective trial of 8,307 patients published by Kakkar et al in the New England Journal of Medicine demonstrated that use of enoxaparin (over a period of 10 ± 4 days) plus elastic stockings with graduated compression, compared with elastic stockings with graduated compression alone, was not associated with a reduction in the rate of death from any cause among hospitalized, acutely ill medical patients. Because of this finding, Kakkar et al questioned the use of extended LMWH treatment following discharge after major urologic surgery, citing the need for further clinical studies.[5] However, patients with bladder cancer have a fivefold higher risk of VTE than the overall population, and when VTE occurs in this setting it triples the mortality risk.[6] This increased risk is propagated further in patients undergoing cystectomy and systemic chemotherapy.[6,7]

The article by Drs. Fantony and Inman in this issue of ONCOLOGY emphasizes the significant risk that VTE poses in patients with bladder cancer, as well the bleeding phenomena that can occur concurrently and result in clinically relevant anemia necessitating a blood transfusion.[8] The balancing act entailed in avoiding both bleeding and clotting risks in these patients can be challenging and requires a special management approach. The authors offer a clear and succinct review of the physiologic mechanisms of the intrinsic and extrinsic coagulation pathways that ultimately culminate in fibrinolysis, and proceed to elucidate the disruption of the coagulation cascade and fibrinolysis pathways that is specific to bladder cancer.

To identify and manage patients at higher risk for VTE, the authors highlight several risk-assessment tools, including the Khorana and Caprini scoring systems, that may be useful in preoperative assessment and medical optimization to reduce VTE risk.[9,10] More importantly the authors emphasize the current guideline recommendations from the American College of Chest Physicians (ACCP), American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and National Comprehensive Cancer Network (NCCN) for VTE prophylaxis in patients with active bladder cancer as well as bladder cancer patients undergoing surgery. In particular, pharmacologic prophylaxis in patients scheduled for cystectomy should be started prior to surgical incision and should continue for 4 weeks postoperatively.[11,12]

Lastly, as Drs. Fantony and Inman discuss, despite the higher risk of VTE in patients with bladder cancer, ironically, their risk of bleeding and anemia, and greater need for transfusion of blood products, poses an equally significant risk of morbidity and mortality, especially among those who undergo cystectomy. Indeed, patients who require perioperative blood transfusions at cystectomy have up to 30% increased overall mortality.[13] The authors highlight important considerations specific to bladder cancer patients in regard to VTE prevention and reduction of bleeding risks, with an emphasis on high-quality surgery by high-volume (high-quality!) surgeons. We support their conclusions and indeed, in our own large, high-volume radical cystectomy practice, AMK routinely advocates early ambulation, institution of DVT chemoprophylaxis as soon as feasible (even prior to induction of anesthesia), and awareness of the risk of VTE in the setting of bladder cancer as the "cornerstones of VTE prevention and early recognition."

Financial Disclosure:Dr. Kamat serves on the advisory boards of Photocure and Sanofi, and receives research funding from FKD and Merck. Dr. Thomas has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

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2. Ruppert A, Steinle T, Lees M. Economic burden of venous thromboembolism: a systematic review. J Med Econ. 2011;14:65-74.

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8. Fantony JJ, Inman BA. Thromboembolism and bleeding in bladder cancer. Oncology (Williston Park). 2014;28:847-62.

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11. Lyman GH, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31:2189-204.

12. Mandala M, Falanga A, Roila F, Group EGW. Management of venous thromboembolism (VTE) in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2011;22(Suppl 6):vi85-92.

13. Linder BJ, Frank I, Cheville JC, et al. The impact of perioperative blood transfusion on cancer recurrence and survival following radical cystectomy. Eur Urol. 2013;63:839-45.