August 04, 2015
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Interaction between prostate cancer, comorbidities increases VTE risk

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High levels of comorbidities considerably increased venous thromboembolism risk among patients with prostate cancer, according to results of a national cohort study.

The clinical interaction between prostate cancer and those comorbidities accounted for nearly one-third of VTEs among that patient population, results showed. Consequently, the ability to reduce VTEs associated with comorbidities may help improve the prognosis of patients with prostate cancer, researchers wrote.

“Approximately 40% of patients with prostate cancer have other chronic conditions at diagnosis,” Anne G. Ording, PhD, clinical epidemiologist at Aarhus University Hospital in Denmark, and colleagues wrote. “Prostate cancer management is complicated by other chronic conditions; and, as prostate cancer survival improves, many patients die of other causes.”

VTE remains a serious complication risk among patients with cancer. However, the extent to which comorbidity interacts clinically with prostate cancer to increase the risk for VTE beyond that explained by disease and comorbidity alone is unknown, according to Ording and colleagues.

The researchers conducted a nationwide registry-based cohort study of all Danish men diagnosed with prostate cancer between 1995 and 2011 (n = 44,035). They matched patients with prostate cancer with 213,810 men from the general population based on age, calendar time and comorbidities. In both cohorts, the researchers excluded all men treated for VTE prior to the index date.

Both cohorts had a median age of 72 years (interquartile range [IQR], 65-78). Sixty-seven percent of men with prostate cancer had no comorbidities at diagnosis. Approximately 15% of patients had a Charlson Comorbidity Index score of 1 or greater.

Ording and colleagues determined VTE rate ratios and the interaction contrast as a measure on the additive scale of the excess VTE rate based on synergy between prostate cancer and comorbidity.

Median follow-up was 3.2 years (IQR, 1.6-5) for the patient cohort and 4.5 years (IQR, 2.4-5) for the matched cohort.

During follow-up, 849 men with prostate cancer and 2,360 men from the matched cohort developed VTE. The researchers calculated the risk for VTE as 2.2% among men with prostate cancer and 1.3% among those in the matched cohort.

Patients with prostate cancer and a high comorbidity level had a 1-year VTE standardized rate of 15 per 1,000 person-years (95% CI, 6.8-24). The interaction between prostate cancer and comorbidity accounted for 29% of that rate.

Men in the prostate cancer cohort exhibited an almost threefold increased VTE risk in the first year of follow-up and a twofold increased risk during subsequent follow-up compared with the matched cohort.

Factors associated with increased VTE risk included age 70 years or older, metastatic disease, and high Gleason scores. Patients who underwent surgery and those in the D’Amico high-risk group also demonstrated increased risk.

Outpatient diagnoses to the Danish National Patient Registry began in 1995. Consequently, the researchers acknowledged the potential inclusion of men who underwent outpatient treatment for VTE prior to the index date as a study limitation.

“Interaction between prostate cancer and comorbidity was observed among patients who had high levels of comorbidity, accounting for 29% of all episodes of VTE,” Ording and colleagues wrote. “Prostate cancer was not a strong risk factor for VTE compared with many other cancers. However, because of the large population burden of prostate cancer, a small reduction in the VTE risk associated with comorbidity may have a positive impact on the prognosis of patients with prostate cancer.”

More research is needed to determine the full extent to which comorbidities influence VTE risk among patients with prostate cancer, Shabbir M.H. Alibhai, MD, MSc, and Meagan E. O’Neill, MSc, both of the department of medicine at University of Toronto’s University Health Network, wrote in an accompanying editorial.

“There are still areas that need to be addressed to obtain a fuller understanding of the risk [for] VTE for men diagnosed with prostate cancer who are undergoing various treatments (surgery, radiation or ADT),” Alibhai and O’Neill wrote. “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.”

Alibhai and O’Neill also identified additional study limitations.

“First, we lack information on the use of thromboprophylaxis; lower use both in men with prostate cancer and in those with greater comorbidity (eg, because of the perceived increased risk [for] bleeding) could partly explain the results,” they wrote. “Second, the highest risk population was also the smallest (about 2% of prostate cancer patients had severe comorbidity), leading to a substantial uncertainty around findings.” – by Cameron Kelsall

Disclosure: The researchers report no relevant financial disclosures. Alibhai and O’Neill report no relevant financial disclosures.