Colorectal Cancer: Aspirin and Colorectal Cancer

Aspirin Benefits May Include Cancer Prevention
Aspirin Benefits May Include Cancer Prevention

By Charles Bankhead, Staff Writer, MedPage Today
Published: March 21, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

Regular aspirin use leads to significant reductions in the risk of cancer, metastasis, and cancer mortality, according to one of the largest-ever analyses of published data.

Overall, aspirin users had a 38% reduction in the risk of colorectal and other gastrointestinal cancers compared with nonusers. Cancer mortality was 15% lower among regular users of aspirin, and metastasis was 35% to 40% less common.

One of the analyses showed a reduced risk of vascular events in patients taking aspirin, but an increased risk of major bleeding. The effects of aspirin on both outcomes declined over time. Fatal extracranial bleeding occurred significantly less often among aspirin users, as reported online in three articles in The Lancet and The Lancet Oncology.

The findings “add to the case for long-term use of aspirin for cancer prevention in middle age in addition to appropriate dietary and lifestyle interventions,” Peter M. Rothwell, FMedSci, of the University of Oxford in England, and co-authors concluded in one of their Lancet articles.

“In view of the very low rates of vascular events in recent and ongoing trials of aspirin in primary prevention, prevention of cancer could become the main justification for aspirin use in this setting, although more research is required to identify which individuals are likely to benefit most.”

Despite the comprehensive nature of the analyses, they did not include the two largest clinical evaluations of aspirin’s effect on cancer risk, noted authors of a commentary published simultaneously in The Lancet. The Women’s Health Initiative and the Physicians’ Health Study involved more than 60,000 men and women, and neither demonstrated an effect of aspirin on cancer risk.

“These caveats notwithstanding, Rothwell and colleagues show quite convincingly that aspirin seems to reduce cancer incidence and death across different subgroups and cancer sites, with an apparent delayed effect,” Andrew T. Chan, MD, and Nancy R. Cook, ScD, of Harvard and Brigham and Women’s Hospital in Boston, wrote.

“Thus, for most individuals, the risk benefit calculus of aspirin seems to favor aspirin’s long-term anti-cancer benefit.”

In the three articles, the authors described cancer-related outcomes from more than 200 randomized, cohort, and case control studies involving several million patients. The investigators performed multiple analyses, which involved various combinations of the trials.

The analysis of cancer mortality encompassed 51 trials (including 34 randomized trials) and more than 100,000 patients.

The principal analysis included 34 trials and 69,224 participants. The results showed a mortality odds ratio of 0.85 in favor of aspirin (P=0.008).

Considering deaths occurring five years or later into the trials, the aspirin advantage increased to 37% (OR 0.63, P=0.0005).

In six trials of low-dose aspirin for primary prevention, cancer incidence was 24% lower with aspirin from 3 years on (P=0.0003) and was significantly lower in both men (OR 0.77, P=0.008) and women (OR 0.75, P=0.01).

Aspirin did not significantly reduce the risk of vascular events nor significantly increase the risk of major bleeding. Major extracranial bleeding did occur less often in patients using low-dose aspirin (OR 0.32, P=0.009) compared with those who did not use aspirin.

The analysis of aspirin and metastatic cancer comprised five randomized trials and a total of 17,285 study participants followed for an average of 6.5 years. The primary objective of each trial was prevention of vascular events.

Overall, randomization to aspirin was associated with a 36% reduction in the hazard for cancer with metastasis (P=0.001), including a 46% reduction in the hazard for metastatic adenocarcinoma (P=0.0007).

Aspirin reduced the risk of metastatic adenocarcinoma at diagnosis (HR 0.69, P=0.02) and during follow-up (HR 0.45, P=0.0009). The greatest benefit occurred in patients with colorectal cancer who did not have metastatic disease at diagnosis (OR 0.26, P=0.0008).

A survival analysis showed that aspirin reduced cancer mortality only in patients with adenocarcinoma (HR 0.65, P=0.0002).

The third article by Rothwell and co-authors described an analysis of 195 case-control and cohort studies of aspirin and cancer risk, which they compared with outcomes from six randomized trials.

In the case-control studies, patients allocated to aspirin had a 38% lower risk of colorectal cancer (OR 0.62, P<0.0001) with minimal heterogeneity among the studies. Similarly consistent effects of aspirin emerged from analyses of esophageal, gastric, biliary, and breast cancer. Comparison with the randomized trials also demonstrated consistent effects. Estimated effects of aspirin in the cohort studies paralleled those of the case-control studies and were consistent with the randomized trials. An analysis limited to studies that stratified by cancer stage at diagnosis showed that regular aspirin use was associated with a 31% reduction in the risk of distant metastasis but not locoregional spread (OR 0.98). Eric Jacobs, PhD, a spokesperson for the American Cancer Society, characterized the analyses as "important new evidence that long-term daily aspirin, even at low doses, may lower the risk of developing cancer." Even so, the decision to initiate regular aspirin use should be individualized after a discussion between patient and physician, he said. "Because these results are new, it will take time for the broader scientific community to evaluate the data in the context of existing knowledge and to consider whether the clinical guidelines should be changed ... Clinical guidelines require a systematic analysis of for whom the benefits of aspirin use are likely to outweigh the risks." These studies found that regular aspirin use leads to significant reductions in the risk of cancer, metastasis, and cancer mortality. Note that despite the comprehensive nature of the analyses, they did not include the two largest clinical evaluations of aspirin's effect on cancer risk, neither of which demonstrated an effect of aspirin on cancer risk. Rothwell disclosed relationships with AstraZeneca, Bayer, Boehringer Ingelheim, sanofi-aventis, Bristol-Myers Squibb, and Servier. Co-authors disclosed relationships with AstraZeneca, Bayer, sanofi-aventis, and Bristol-Myers Squibb. Primary source: The Lancet Source reference: Rothwell PR, et al "Short-term effects of daily aspirin on cancer incidence, mortalilty, and nonvascular death: Analysis of the time course of risks and benefits in 51 randomized controlled trials" Lancet 2012; DOI: 10.1016/S01450-6736(11)61720-0. Additional source: The Lancet Source reference: Rothwell PM, et al "Effect of daily aspirin on risk of cancer metastasis: A study of incident cancers during randomized controlled trials" Lancet 2012; DOI: 10.1016/S0140-6736(12)60209-8. Additional source: The Lancet Oncology Source reference: Rothwell PM, et al "Effects of regular aspirin on long-term cancer incidence and metastasis: A systematic comparison of evidence from observational studies versus randomized trials" Lancet Oncol 2012; DOI: 10.1016/S1470-2045(12)70112-2.

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