Comorbidity and the risk of venous thromboembolism in prostate cancer.

Venous thromboembolism (VTE) includes the development of deep vein thrombosis (DVT) and pulmonary embolism (PE). VTE is common in the general population (risk, 118 per 100,000 person-years), and PE is associated with a 30% risk of death within 3 months. Important risk factors for VTE include increasing age, recent surgery, and malignancy. Additional VTE risk factors include trauma, institutionalization, and specific comorbidities, including myocardial infarction, congestive heart failure, chronic obstructive pulmonary disease, and certain neurologic disorders. Effective and safe thromboprophylaxis and treatment exist. VTE is particularly important in the cancer population. Individuals with a diagnosis of cancer have a 4-fold increased risk of developing VTE. The frequency of VTE is higher in the first year after a diagnosis of cancer. In addition, survival among individuals with cancer who have a VTE is 3 times worse than that among individuals who have cancer and no occurrence of VTE. Not only does a diagnosis of cancer increase the risk of VTE: site, stage, and treatment all appear to influence the risk. Among cancer sites, high-risk cancer types include brain, lung, and pancreatic and other digestive cancers. Prostate cancers (PCs), as well as breast and colorectal cancers, are considered to fall within the low-risk category compared with most other malignancies. As disease stage progresses, so too does the likelihood of VTE occurrence. Furthermore, treatment for the disease can also impact the risk of VTE occurrence; surgery and chemotherapy increase the risk of VTE, whereas radiation is not typically considered a risk factor. The major risk factors for VTE in the general population and the overall cancer population hold true for men with PC. Age and active malignancy increase the risk of VTE, and recent surgery is associated with a 5-fold to 7-fold increased risk. Like all cancer types, more advanced stage is associated with an increased risk of VTE. Additional factors that can increase the risk of VTE in men with PC include a previous history of VTE, blood transfusion, ABO blood type, the number of lymph nodes removed during surgery, and receipt of androgen-deprivation therapy (ADT). ADT in particular deserves special comment, because it is received by up to 1 in 2 men with PC and may increase the risk of both arterial thromboembolism and VTE by up to 50%. Both treatment and duration of ADT increase an individual’s risk of a VTE occurrence. There are still areas that need to be addressed to obtain a fuller understanding of the risk of VTE for men diagnosed with PC who are undergoing various treatments (surgery, radiation, or ADT). Although some risk factors have been identified consistently across multiple studies, including increasing age, recent surgery, and active malignancy, the role of other risk factors, such as blood type, vascular or neurologic disorders, other comorbidities, and receipt of ADT, needs to be evaluated further. What is not so clear is how these VTE risk factors interact with one another. Risk factors (eg, PC, comorbidity) for a given outcome (eg, VTE) can interact in 1 of 3 main ways: they may be additive, multiplicative, or partially offset one another. Although much of conventional medicine features additive risk factor models, there are important exceptions. For example, in the world of inheritable thrombophilias and VTE risk, being heterozygous for Factor V Leiden (FVL) is associated with a 4-fold increased risk of VTE, whereas being homozygous is associated with an 11-fold increased risk. Family members who are heterozygous for the FVL mutation have a 3.5-fold increased risk of VTE, but those who are homozygous have a whopping 18-fold increased risk. Understanding the relation between risk factors may have important implications for counseling, screening, and prophylaxis.