On the basis of long-term follow-up data from the National Polyp Study, the authors estimate that mortality from colorectal cancer was about 50% lower among patients who had adenomatous polyps ...removed than in the general population.
It has been a long-standing belief that screening for colorectal cancer can affect mortality from the disease in two ways: by detecting cancers at an early, curable stage and by detecting and removing adenomas.
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Detection of early-stage colorectal cancer has been shown to be associated with a reduction in mortality from colorectal cancer in screening trials.
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However, an adenomatous polyp is a much more common neoplastic finding on endoscopic screening. We previously reported that colonoscopic polypectomy in the National Polyp Study (NPS) cohort reduced the incidence of colorectal cancer.
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An important question is whether the cancers prevented by colonoscopic . . .
Abstract Purpose Screening is a major contributor to colorectal cancer (CRC) mortality reductions in the United States but is underused. We estimated the fraction of CRC deaths attributable to nonuse ...of screening to demonstrate the potential benefits from targeted interventions. Methods The established microsimulation screening analysis colon model was used to estimate the population attributable fraction (PAF) in people aged ≥50 years. The model incorporates long-term patterns and effects of screening by age and type of screening test. PAF for 2010 was estimated using currently available data on screening uptake. PAF was also projected assuming constant future screening rates to incorporate lagged effects from past increases in screening uptake. We also computed PAF using Levin's formula to gauge how this simpler approach differs from the model-based approach. Results There were an estimated 51,500 CRC deaths in 2010, about 63% (N ∼ 32,200) of which were attributable to nonscreening. The PAF decreases slightly to 58% in 2020. Levin's approach yielded a considerably more conservative PAF of 46% (N ∼ 23,600) for 2010. Conclusions Most of the current United States CRC deaths are attributable to nonscreening. This underscores the potential benefits of increasing screening uptake in the population. Traditional methods of estimating PAF underestimated screening effects compared with model-based approaches.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In a population-based sample of cervical cancer survivors, health-related quality of life (HRQoL) was assessed 2-10 years postdiagnosis.
All patients given a diagnosis of cervical cancer in 1995-2003 ...in the Eindhoven region, The Netherlands, and alive after Jan 2006 were identified through the cancer registry. Generic HRQoL (36-Item Short-Form Health Survey, EQ-5D), cervical cancer-specific HRQoL (European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire cervical cancer module), and anxiety (6-item State Trait Anxiety Inventory) were assessed and compared with a reference population (n = 349). Data for tumor characteristics at diagnosis and disease progression were available.
A total of 291 women responded (69%), with a mean age of 53 +/- 13 (SD) years (range, 31-88 years). Treatment had consisted of surgery (n = 195) or a combination of therapies (n = 75); one woman had not been treated. Of all women, 85% were clinically disease free, 2% had a recurrence/metastasis, and in 13%, this was unknown. After controlling for background characteristics (age, education, job and marital status, having children, and country of birth), generic HRQoL scale scores were similar to the reference population, except for worse mental health in survivors. The most frequent symptoms were crampy pain in the abdomen or belly (17%), urinary leakage (15%), menopausal symptoms (18%), and problems with sexual activity. Compared with the 6-10-year survivors, more sexual worry and worse body image were reported by the 2-5-year survivors. Compared with surgery only, especially primary radiotherapy was associated with an increased frequency of treatment-related side effects, also after controlling for age and disease stage at diagnosis and follow-up.
Most cervical cancer survivors were coping well, although their mental health was worse than in the reference population. Even after 2-10 years, radiotherapy was associated with an increased frequency of treatment-related side effects.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Summary Background Screening for colorectal cancer is widely recommended, but the preferred strategy remains unidentified. We aimed to compare participation and diagnostic yield between screening ...with colonoscopy and with non-cathartic CT colonography. Methods Members of the general population, aged 50–75 years, and living in the regions of Amsterdam or Rotterdam, identified via the registries of the regional municipal administration, were randomly allocated (2:1) to be invited for primary screening for colorectal cancer by colonoscopy or by CT colonography. Randomisation was done per household with a minimisation algorithm based on age, sex, and socioeconomic status. Invitations were sent between June 8, 2009, and Aug 16, 2010. Participants assigned to CT colonography who were found to have one or more large lesions (≥10 mm) were offered colonoscopy; those with 6–9 mm lesions were offered surveillance CT colonography. The primary outcome was the participation rate, defined as number of invitees undergoing the examination relative to the total number of invitees. Diagnostic yield was calculated as number of participants with advanced neoplasia relative to the total number of invitees. Invitees and screening centre employees were not masked to allocation. This trial is registered in the Dutch trial register, number NTR1829. Findings 1276 (22%) of 5924 colonoscopy invitees participated, compared with 982 (34%) of 2920 CT colonography invitees (relative risk RR 1·56, 95% CI 1·46–1·68; p<0·0001). Of the participants in the colonoscopy group, 111 (9%) had advanced neoplasia of whom seven (<1%) had a carcinoma. Of CT colonography participants, 84 (9%) were offered colonoscopy, of whom 60 (6%) had advanced neoplasia of whom five (<1%) had a carcinoma; 82 (8%) were offered surveillance. The diagnostic yield for all advanced neoplasia was 8·7 per 100 participants for colonoscopy versus 6·1 per 100 for CT colonography (RR 1·46, 95% CI 1·06–2·03; p=0·02) and 1·9 per 100 invitees for colonoscopy and 2·1 per 100 invitees for CT colonography (RR 0·91, 0·66–2·03; p=0·56). The diagnostic yield for advanced neoplasia of 10 mm or more was 1·5 per 100 invitees for colonoscopy and 2·0 per 100 invitees for CT colonography, respectively (RR 0·74, 95% CI 0·53–1·03; p=0·07). Serious adverse events related to the screening procedure were post-polypectomy bleedings: two in the colonoscopy group and three in the CT colonography group. Interpretation Participation in colorectal cancer screening with CT colonography was significantly better than with colonoscopy, but colonoscopy identified significantly more advanced neoplasia per 100 participants than did CT colonography. The diagnostic yield for advanced neoplasia per 100 invitees was similar for both strategies, indicating that both techniques can be used for population-based screening for colorectal cancer. Other factors such as cost-effectiveness and perceived burden should be taken into account when deciding which technique is preferable. Funding Netherlands Organisation for Health Research and Development, Centre for Translational Molecular Medicine, and the Nuts Ohra Foundation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Pancreatic cancer (PC) survival is poor, as detection usually occurs late, when treatment options are limited. Screening of high‐risk individuals may enable early detection and a more favorable ...prognosis. Knowledge gaps prohibit establishing the effectiveness of screening. We developed a Microsimulation Screening Analysis model to analyze the impact of relevant uncertainties on the effect of PC screening in high‐risk individuals. The model simulates two base cases: one in which lesions always progress to PC and one in which indolent and faster progressive lesions coexist. For each base case, the effect of annual and 5‐yearly screening with endoscopic ultrasonography/magnetic resonance imaging was evaluated. The impact of variance in PC risk, screening test characteristics and surgery‐related mortality was evaluated using sensitivity analyses. Screening resulted in a reduction of PC mortality by at least 16% in all simulated scenarios. This reduction depended strongly on the natural disease course (annual screening: −57% for “Progressive‐only” vs −41% for “Indolent Included”). The number of screen and surveillance tests needed to prevent one cancer death was impacted most by PC risk. A 10% increase in test sensitivity reduced mortality by 1.9% at most. Test specificity is important for the number of surveillance tests. In conclusion, screening reduces PC mortality in all modeled scenarios. The natural disease course and PC risk strongly determines the effectiveness of screening. Test sensitivity seems of lesser influence than specificity. Future research should gain more insight in PC pathobiology to establish the true value of PC screening in high‐risk individuals.
What's new?
About 10 percent of pancreatic cancers occur in individuals with inherited risk factors. While screening such high‐risk individuals can facilitate the detection of precursor lesions and early‐stage cancer, the extent to which benefits outweigh harms, including overdiagnosis, remains unknown. Here, using a microsimulation model, the authors explored uncertainties concerning the early detection of pancreatic cancer and analyzed the impact of these uncertainties on the effect of screening. In all simulated scenarios, screening was associated with reduced pancreatic cancer mortality. The effectiveness of screening was most strongly impacted by characteristics of natural disease course and level of pancreatic cancer risk
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The ColonCancerCheck screening program for colorectal cancer (CRC) in Ontario, Canada, is considering switching from biennial guaiac fecal occult blood test (gFOBT) screening between age 50-74 years ...to the more sensitive, but also less specific fecal immunochemical test (FIT). The aim of this study is to estimate whether the additional benefits of FIT screening compared to gFOBT outweigh the additional costs and harms.
We used microsimulation modeling to estimate quality adjusted life years (QALYs) gained and costs of gFOBT and FIT, compared to no screening, in a cohort of screening participants. We compared strategies with various age ranges, screening intervals, and cut-off levels for FIT. Cost-efficient strategies were determined for various levels of available colonoscopy capacity.
Compared to no screening, biennial gFOBT screening between age 50-74 years provided 20 QALYs at a cost of CAN$200,900 per 1,000 participants, and required 17 colonoscopies per 1,000 participants per year. FIT screening was more effective and less costly. For the same level of colonoscopy requirement, biennial FIT (with a high cut-off level of 200 ng Hb/ml) between age 50-74 years provided 11 extra QALYs gained while saving CAN$333,300 per 1000 participants, compared to gFOBT. Without restrictions in colonoscopy capacity, FIT (with a low cut-off level of 50 ng Hb/ml) every year between age 45-80 years was the most cost-effective strategy providing 27 extra QALYs gained per 1000 participants, while saving CAN$448,300.
Compared to gFOBT screening, switching to FIT at a high cut-off level could increase the health benefits of a CRC screening program without considerably increasing colonoscopy demand.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
The natural history of human papillomavirus (HPV)-induced cervical cancer (CC) is not directly observable, yet the age of HPV acquisition and duration of preclinical disease ...(dwell time) influences the effectiveness of alternative preventive policies. We performed a Cancer Intervention and Surveillance Modeling Network (CISNET) comparative modeling analysis to characterize the age of acquisition of cancer-causing HPV infections and implied dwell times for distinct phases of cervical carcinogenesis.
Methods
Using four CISNET-cervical models with varying underlying structures but fit to common US epidemiological data, we estimated the age of acquisition of causal HPV infections and dwell times associated with three phases of cancer development: HPV, high-grade precancer, and cancer sojourn time. We stratified these estimates by HPV genotype under both natural history and CC screening scenarios, because screening prevents cancer development that affects the mix of detected cancers.
Results
The median time from HPV acquisition to cancer detection ranged from 17.5 to 26.0 years across the four models. Three models projected that 50% of unscreened women acquired their causal HPV infection between ages 19 and 23 years, whereas one model projected these infections occurred later (age 34 years). In the context of imperfect compliance with US screening guidelines, the median age of causal infection was 4.4–15.9 years later compared with model projections in the absence of screening.
Conclusions
These validated CISNET-CC models, which reflect some uncertainty in the development of CC, elucidate important drivers of HPV vaccination and CC screening policies and emphasize the value of comparative modeling when evaluating public health policies.
Background & Aims Colorectal cancer (CRC) screening decisions for elderly individuals are often made primarily on the basis of age, whereas other factors that influence the effectiveness and cost ...effectiveness of screening are often not considered. We investigated the relative importance of factors that could be used to identify elderly individuals most likely to benefit from CRC screening and determined the maximum ages at which screening remains cost effective based on these factors. Methods We used a microsimulation model (Microsimulation Screening Analysis-Colon) calibrated to the incidence of CRC in the United States and the prevalence of adenomas reported in autopsy studies to determine the appropriate age at which to stop colonoscopy screening in 19,200 cohorts (of 10 million individuals), defined by sex, race, screening history, background risk for CRC, and comorbidity status. We applied a willingness-to-pay threshold of $100,000 per quality-adjusted life-year (QALY) gained. Results Less intensive screening history, higher background risk for CRC, and fewer comorbidities were associated with cost-effective screening at older ages. Sex and race had only a small effect on the appropriate age to stop screening. For some individuals likely to be screened in current practice (for example, 74-year-old white women with moderate comorbidities, half the average background risk for CRC, and negative findings from a screening colonoscopy 10 years previously), screening resulted in a loss of QALYs, rather than a gain. For some individuals unlikely to be screened in current practice (for example, 81-year-old black men with no comorbidities, an average background risk for CRC, and no previous screening), screening was highly cost effective. Although screening some previously screened, low-risk individuals was not cost effective even when they were 66 years old, screening some healthy, high-risk individuals remained cost effective until they reached the age of 88 years old. Conclusions The current approach to CRC screening in elderly individuals, in which decisions are often based primarily on age, is inefficient, resulting in underuse of screening for some and overuse of screening for others. CRC screening could be more effective and cost effective if individual factors for each patient are considered.
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