Inflammation control vs cancer risk in ulcerative colitis: The treatment decisions that matter
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The thing that stands out the most in my years treating surgical patients is how many of them came into the OR with completely preventable damage.
—Jason Schroder, DO
Ulcerative colitis is no longer viewed only through symptoms and flares. Long-term mortality risk is driven by two factors that clinicians still underestimate in routine care: colorectal cancer and venous thromboembolism.
Both are closely tied to inflammatory burden and treatment decisions over time.
Colorectal cancer risk is linked to duration and control
IBD is associated with a 17% to 54% higher risk of overall cancer incidence and a 26% higher risk of cancer-related death compared to the general population. [] [] [] []
Chronic colonic inflammation drives dysplasia. Risk increases with disease duration, extent, and severity. Historical data show a cumulative colorectal cancer risk of about 2% at 10 years, rising to 5% to 8% at 20 years, and up to 18% at 30 years in long-standing disease. []
More recent cohorts show lower rates, reflecting better disease control and surveillance, though risk persists, especially in extensive colitis. []
Extent matters. Patients with pancolitis carry a higher risk than those with left-sided disease. Persistent histologic inflammation further increases risk, even when symptoms are controlled. []
This shifts how therapy is selected. Patients with extensive disease or ongoing inflammation require earlier optimization of therapy, not repeated cycles of steroids or partial control. Jason Schroder, DO, a board-certified anesthesiologist, says, “Chronic inflammation deep in the wall of the bowel, the type that lasts for months or years without treatment, causes the fibrosis and dysplasia to develop…and no drug reverses that once it occurs.”
Surveillance alone is not enough
Colonoscopy detects dysplasia. It does not prevent it. Disease control reduces risk. Dr. Schroder adds, “The thing that stands out the most in my years treating surgical patients is how many of them came into the OR with completely preventable damage.”
Further, he says, “Strictures and fistulas are the most common permanent consequences that I see in under-treated IBD that both develop quietly, long before a patient reports feeling worse.”
Related: Treat-to-target in Crohn’s and UC: Optimizing therapy, de-escalating thiopurines, and defining steroid thresholdsVenous thromboembolism is a major driver of mortality
The thrombotic risk in UC remains under-recognized in outpatient care. Patients with inflammatory bowel disease have a two- to fourfold higher risk of venous thromboembolism compared with the general population. []
Risk increases further during active disease and hospitalization. In one cohort, in-hospital mortality was 10.26% in patients with VTE compared with 2.28% without VTE. []
Long-term mortality also remained higher in patients with thromboembolic events. This risk extends even into the post-discharge period and correlates with inflammatory activity. []
Steroid exposure adds to the risk. Prolonged corticosteroid use is associated with increased thrombotic events and infection risk.
Therapy selection directly influences risk
Persistent inflammation drives both cancer risk and thromboembolism, but advanced therapies with sustained anti-inflammatory effect can reduce cumulative exposure to active disease. This includes biologics and small molecules used earlier in the disease course.
JAK inhibitors introduce a different consideration. While effective for rapid control, they are traditionally believed to carry a known signal for thromboembolic risk, particularly in higher-risk populations. Patient selection and risk stratification remain critical.
However, most data on JAK inhibitors’ cancer and DVT risks comes from research done in rheumatoid arthritis patients. [] [] [] []
According to board-certified gastroenterologist Raymond K. Cross, Jr., MD, MS, AGAF, FACG, who is Medical Director of The Center for Inflammatory Bowel and Colorectal Diseases at Mercy in Baltimore, this risk might be “overestimated” in many cases.
As he explained, “I routinely review a patient's problem list for MACE and prior DVT/PE before starting any new therapy….The biggest misconception is the magnitude of risk. In older adults with arthritis on a different JAK inhibitor, there was a 1% absolute increase of MACE, 1% absolute increase risk of cancer, and 1/300 increased risk in DVT/PE. In that study, if patients did not have a history of MACE or DVT, their risk was not increased. If they were under 65 and never smoked, they had no increased risk of cancer. Patients with UC and Crohn's disease have not been found to have a higher risk of these complications in the clinical trials or real-world studies. As I mentioned above, I do think safety is a class-wide effect, but the risks are overestimated.”
Monitoring must match risk
Patients with long-standing disease require structured colorectal cancer surveillance. This includes regular colonoscopy with targeted biopsies.
Thromboembolism prevention requires attention during flares and hospitalizations. Pharmacologic VTE prophylaxis is recommended for hospitalized patients with IBD, particularly during active disease, using low-molecular-weight or unfractionated heparin unless contraindicated. This approach, however, remains underused. []
Related: Applying Montreal classification and progression red flags in IBD: When phenotype should trigger escalation