Prevention of Colorectal Cancer With Low-dose Aspirin
Prevention of Colorectal Cancer With Low-dose Aspirin
Objective Low-dose aspirin reduces colorectal cancer (CRC) incidence and mortality. Recently, the aspirin effect has been shown to occur primarily in the proximal colon. Colonoscopy has been either less effective or ineffective in the proximal compared to the distal colon. The authors assessed the cost-effectiveness of adding low-dose aspirin to a simulated screening with colonoscopy or sigmoidoscopy.
Design A Markov model comparing the strategies of 10-year colonoscopy or sigmoidoscopy screening and the combination of either of the two with low-dose aspirin in 100 000 subjects aged 50 years until death was constructed. Proximal and distal CRC prevention rates with endoscopy or aspirin were extracted from the literature. Screening and aspirin prevention were simulated to stop at 80 years. The cost of aspirin and aspirin-related complications, as well as aspirin-related mortality, was included. Incremental cost-effectiveness ratios between the different strategies were calculated. Sensitivity and probabilistic analyses were also performed.
Results The addition of low-dose aspirin to colonoscopy and sigmoidoscopy screening increased the CRC death prevention rate from 68% and 39% to 81% and 69%, respectively. Lifetime aspirin-related mortality appeared to be 0.1%. Because of the substantial reduction in CRC care, the addition of aspirin to colonoscopy and sigmoidoscopy screening was cost-effective (incremental cost-effectiveness ratio: US$5413 per life-year saved) and cost saving (US$278 per person), respectively. When the proximal CRC prevention rate with colonoscopy was increased 56% to 73% from the baseline, the addition of aspirin was no longer cost-effective. The addition of aspirin to colonoscopy and sigmoidoscopy was a cost-effective strategy in 52% and 94% of the scenarios at probabilistic analysis.
Conclusions When assuming a suboptimal efficacy of endoscopy in preventing CRC, the addition of low-dose aspirin may be an effective and cost-effective strategy, mainly because of its high efficacy in preventing proximal CRC.
Colorectal cancer (CRC) represents a major cause of morbidity and mortality in Western countries, also resulting in a substantial economic burden due to costs for surgery, chemotherapy and terminal care.
In a 20-year follow-up of high-quality randomised trials on cardiovascular prevention including over 14 000 patients, ≥5-year treatment with low-dose aspirin (75–300 mg daily) was shown to reduce CRC incidence and mortality by 38% and 52%, respectively. This result was consistent with previous randomised and observational studies showing the efficacy of high-dose aspirin in preventing CRC/adenoma incidence in patients at average or increased risk of CRC. The effect of low-dose aspirin also appeared to be site-specific, resulting in a high rate of proximal CRC prevention, while no distal CRC prevention was observed. Compared to high-dose aspirin, which has also been effective in preventing CRC, low-dose aspirin may also be expected to reduce aspirin toxicity, including its potentially life-threatening side effects.
CRC screening by means of endoscopy has been shown to prevent CRC incidence and mortality. This has been related to the efficacy of polypectomy in preventing CRC incidence and the increase in 5-year CRC survival because of early diagnosis of already-developed CRC. A high-quality randomised trial showed the efficacy of flexible sigmoidoscopy in reducing CRC incidence and mortality by 33% and 43%, respectively, in screening-attendant average-risk subjects. A substantial difference between distal and proximal CRC protection by colonoscopy screening has also been shown. While confirming a substantial reduction in distal CRC incidence and mortality, population-based studies found a reduced, if any, prevention of proximal CRC. This effect was operator dependent, and gastroenterologists achieved better protection in the proximal colon than did surgeons and primary care physicians performing colonoscopy. In a German-based study, colonoscopy by gastroenterologists produced a 56% reduction in proximal cancer and an 84% reduction in distal cancer. Thus, colonoscopy has been either less effective or ineffective in preventing right-sided compared to left-sided cancer, with the variation likely explained by operator performance.
No randomised trial compared the potential efficacy and costs of a primary CRC prevention with low-dose aspirin with those of an endoscopic screening, preventing definitive assumptions on the relative efficacy and interaction between the two strategies. Microsimulation models may partially compensate for the lack of clinical data, simulating the comparison and possible interaction among different preventive strategies based on the available, albeit incomplete, knowledge.
The aim of this cost-effectiveness analysis was to assess the efficacy and costs of CRC primary prevention with low-dose aspirin in average-risk subjects, also assessing its potential interaction with an endoscopic screening, when assuming subsite-specific efficacies for the different strategies.
Abstract and Introduction
Abstract
Objective Low-dose aspirin reduces colorectal cancer (CRC) incidence and mortality. Recently, the aspirin effect has been shown to occur primarily in the proximal colon. Colonoscopy has been either less effective or ineffective in the proximal compared to the distal colon. The authors assessed the cost-effectiveness of adding low-dose aspirin to a simulated screening with colonoscopy or sigmoidoscopy.
Design A Markov model comparing the strategies of 10-year colonoscopy or sigmoidoscopy screening and the combination of either of the two with low-dose aspirin in 100 000 subjects aged 50 years until death was constructed. Proximal and distal CRC prevention rates with endoscopy or aspirin were extracted from the literature. Screening and aspirin prevention were simulated to stop at 80 years. The cost of aspirin and aspirin-related complications, as well as aspirin-related mortality, was included. Incremental cost-effectiveness ratios between the different strategies were calculated. Sensitivity and probabilistic analyses were also performed.
Results The addition of low-dose aspirin to colonoscopy and sigmoidoscopy screening increased the CRC death prevention rate from 68% and 39% to 81% and 69%, respectively. Lifetime aspirin-related mortality appeared to be 0.1%. Because of the substantial reduction in CRC care, the addition of aspirin to colonoscopy and sigmoidoscopy screening was cost-effective (incremental cost-effectiveness ratio: US$5413 per life-year saved) and cost saving (US$278 per person), respectively. When the proximal CRC prevention rate with colonoscopy was increased 56% to 73% from the baseline, the addition of aspirin was no longer cost-effective. The addition of aspirin to colonoscopy and sigmoidoscopy was a cost-effective strategy in 52% and 94% of the scenarios at probabilistic analysis.
Conclusions When assuming a suboptimal efficacy of endoscopy in preventing CRC, the addition of low-dose aspirin may be an effective and cost-effective strategy, mainly because of its high efficacy in preventing proximal CRC.
Introduction
Colorectal cancer (CRC) represents a major cause of morbidity and mortality in Western countries, also resulting in a substantial economic burden due to costs for surgery, chemotherapy and terminal care.
In a 20-year follow-up of high-quality randomised trials on cardiovascular prevention including over 14 000 patients, ≥5-year treatment with low-dose aspirin (75–300 mg daily) was shown to reduce CRC incidence and mortality by 38% and 52%, respectively. This result was consistent with previous randomised and observational studies showing the efficacy of high-dose aspirin in preventing CRC/adenoma incidence in patients at average or increased risk of CRC. The effect of low-dose aspirin also appeared to be site-specific, resulting in a high rate of proximal CRC prevention, while no distal CRC prevention was observed. Compared to high-dose aspirin, which has also been effective in preventing CRC, low-dose aspirin may also be expected to reduce aspirin toxicity, including its potentially life-threatening side effects.
CRC screening by means of endoscopy has been shown to prevent CRC incidence and mortality. This has been related to the efficacy of polypectomy in preventing CRC incidence and the increase in 5-year CRC survival because of early diagnosis of already-developed CRC. A high-quality randomised trial showed the efficacy of flexible sigmoidoscopy in reducing CRC incidence and mortality by 33% and 43%, respectively, in screening-attendant average-risk subjects. A substantial difference between distal and proximal CRC protection by colonoscopy screening has also been shown. While confirming a substantial reduction in distal CRC incidence and mortality, population-based studies found a reduced, if any, prevention of proximal CRC. This effect was operator dependent, and gastroenterologists achieved better protection in the proximal colon than did surgeons and primary care physicians performing colonoscopy. In a German-based study, colonoscopy by gastroenterologists produced a 56% reduction in proximal cancer and an 84% reduction in distal cancer. Thus, colonoscopy has been either less effective or ineffective in preventing right-sided compared to left-sided cancer, with the variation likely explained by operator performance.
No randomised trial compared the potential efficacy and costs of a primary CRC prevention with low-dose aspirin with those of an endoscopic screening, preventing definitive assumptions on the relative efficacy and interaction between the two strategies. Microsimulation models may partially compensate for the lack of clinical data, simulating the comparison and possible interaction among different preventive strategies based on the available, albeit incomplete, knowledge.
The aim of this cost-effectiveness analysis was to assess the efficacy and costs of CRC primary prevention with low-dose aspirin in average-risk subjects, also assessing its potential interaction with an endoscopic screening, when assuming subsite-specific efficacies for the different strategies.
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