Illustration of a blood clot in a vein to represent the risks of venous thromboembolism blood clots

A large Swedish study has shown that people undergoing surgery for cancer have an increased risk for venous thromboembolism (VTE) that persists for about two to four months postoperatively but varies by cancer type.

“The results highlight the need for individualized venous thromboembolism risk evaluation and prophylaxis regimens for patients undergoing different surgery for different cancers,” writes Johan Björklund, M.D., Ph.D., of the Karolinska Institutet in Stockholm, and co-authors in JAMA Network Open.

They explain that major surgery and cancer are both risk factors for VTE, which comprises pulmonary embolism and deep vein thrombosis (DVT). Many clinical guidelines recommend extended prophylactic use of low molecular-weight heparin or other anticoagulants for patients undergoing cancer surgery, but these recommendations are not based on precise estimates of disease-specific excess risk for VTE.

To provide more specific estimates, Björklund and team carried out a registry-based study that included data for 432,218 people (median age, 67 years; 68.7% women) who underwent major surgery for cancer of the bladder, breast, colon or rectum, gynecologic organs, kidney and upper urothelial tract, lung, prostate, or gastroesophageal tract in Sweden between 1998 and 2016. Their 1-year cumulative risk for VTE was compared with that of 4,009,343 cancer-free members of the general population matched by birth year, sex, and county of residence.

The researchers report that the crude 1-year cumulative risk for VTE was significantly higher among the people undergoing cancer surgery than in the general population for all cancer types.

Overall, 1.3% of people in the cancer surgery cohort had a pulmonary embolism within 1 year compared with 0.2% of those in the comparison cohort. For DVT, the corresponding rates were 2.0% and 0.3%.

The excess risk for pulmonary embolism was greatest for people undergoing bladder cancer surgery at 2.69 percentage points and lowest for those undergoing prostate cancer surgery at 0.57 percentage points. Similarly, people undergoing bladder cancer surgery had the greatest excess risk for DVT, at 4.67 percentage points, while those undergoing prostate cancer surgery had the lowest excess risk, at 0.75 percentage points.

The risks for both pulmonary embolism and DVT peaked just after discharge and generally plateaued 60 to 90 days later.

“Although venous thromboembolism is most common in the period covered by standard prophylactic regimens, the transient peak of the rate of venous events is, in general, of longer duration than such regimens, including extended prophylaxes,” the investigators write.

“The clinical significance [of these findings] varies between the different cancer surgeries,” says Björklund. He tells Inside Precision Medicine: “All absolute risks were statistically significant but the absolute risk increase at certain timepoints were was small for some cancers (i.e. breast cancer) and large for some cancers (i.e. bladder and lung). This highlights that not all VTE preventions should be that same in all cancer surgeries.”

He adds that even where the absolute difference is very small, the study still provides relevant information to guide VTE risk assessment.

The researchers also compared the cancer surgery cohort with a noncancer surgery cohort that included individuals who underwent benign prostate, kidney, gynecologic, and colorectal cancer surgery.

“When compared to the benign surgery cohort, we no longer see any increase in cause-specific hazard for prostate and kidney cancer surgery and even a lower hazard in the first 60 days for gynecological and colorectal cancer surgery,” Björklund remarks. “These results indicate that the initial rate increase in our main results is likely due to surgery rather than cancer.”

“For the later part we believe that more cancer specific factors such as neoadjuvant and adjuvant chemotherapies as well as tumor stage can play a role.”

The researchers are now planning future studies to evaluate individualized prophylactic regimens for VTE by taking the degree of surgical trauma caused by, for example, minimally invasive surgery, addition of lymph node dissection, and addition of a stoma, into account as well as disease severity, and exposure to systemic chemotherapy.

“Our observational data alone cannot […] bring about a change in clinical practice,” they write.

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