Strategies for Colorectal Cancer Screening Ladabaum, Uri; Dominitz, Jason A.; Kahi, Charles ...
Gastroenterology (New York, N.Y. 1943),
January 2020, 2020-01-00, 20200101, Letnik:
158, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The incidence of colorectal cancer (CRC) is increasing worldwide. CRC has high mortality when detected at advanced stages, yet it is also highly preventable. Given the difficulties in implementing ...major lifestyle changes or widespread primary prevention strategies to decrease CRC risk, screening is the most powerful public health tool to reduce mortality. Screening methods are effective but have limitations. Furthermore, many screen-eligible people remain unscreened. We discuss established and emerging screening methods, and potential strategies to address current limitations in CRC screening. A quantum step in CRC prevention might come with the development of new screening strategies, but great gains can be made by deploying the available CRC screening modalities in ways that optimize outcomes while making judicious use of resources.
The American Cancer Society has recommended initiating colorectal cancer (CRC) screening at age 45 years instead of 50 years. We estimated the cost effectiveness and national effects of adopting this ...recommendation.
We compared screening strategies and alternative resource allocations in a validated Markov model. We based national projections on screening participation rates by age and census data.
Screening colonoscopy initiation at age 45 years instead of 50 years in 1000 persons averted 4 CRCs and 2 CRC deaths, gained 14 quality-adjusted life-years (QALYs), cost $33,900/QALY gained, and required 758 additional colonoscopies. These 758 colonoscopies could instead be used to screen 231 currently unscreened 55-year-old persons or 342 currently unscreened 65-year-old persons, through age 75 years. These alternatives averted 13–14 CRC cases and 6–7 CRC deaths and gained 27–28 discounted QALYs while saving $163,700–$445,800. Improving colonoscopy completion rates after abnormal results from a fecal immunochemical test yielded greater benefits and savings. Initiation of fecal immunochemical testing at age 45 years instead of 50 years cost $7700/QALY gained. Shifting current age-specific screening rates to 5 years earlier could avert 29,400 CRC cases and 11,100 CRC deaths over the next 5 years but would require 10.7 million additional colonoscopies and cost an incremental $10.4 billion. Improving screening rates to 80% in persons who are 50–75 years old would avert nearly 3-fold more CRC deaths at one third the incremental cost.
In a Markov model analysis, we found that starting CRC screening at age 45 years is likely to be cost effective. However, greater benefit, at lower cost, could be achieved by increasing participation rates for unscreened older and higher-risk persons.
Display omitted
IMPORTANCE: Individuals with adenomatous polyps are advised to undergo repeated colonoscopy surveillance to prevent subsequent colorectal cancer (CRC), but the relationship between adenomas at ...colonoscopy and long-term CRC incidence is unclear. OBJECTIVE: To compare long-term CRC incidence by colonoscopy adenoma findings. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, prospective cohort study of participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer randomized clinical trial of flexible sigmoidoscopy (FSG) beginning in 1993 with follow-up for CRC incidence to 2013 across the United States. Participants included 154 900 men and women aged 55 to 74 years enrolled in PLCO of whom 15 935 underwent colonoscopy following their first positive FSG screening result. The final day of follow-up was December 31, 2013. EXPOSURES: Enrolled participants had been randomized to FSG or usual care. Participants who underwent FSG and had abnormal findings were referred for follow-up. Subsequent colonoscopy findings were categorized as advanced adenoma (≥1 cm, high-grade dysplasia, or tubulovillous or villous histology), nonadvanced adenoma (<1 cm without advanced histology), or no adenoma. MAIN OUTCOMES AND MEASURES: The primary outcome was CRC incidence within 15 years of the baseline colonoscopy. The secondary outcome was CRC mortality. RESULTS: There were 15 935 participants who underwent colonoscopy (men, 59.7%; white, 90.7%; median age, 64 y IQR, 61-68). On initial colonoscopy, 2882 participants (18.1%) had an advanced adenoma, 5068 participants (31.8%) had a nonadvanced adenoma, and 7985 participants (50.1%) had no adenoma; median follow-up for CRC incidence was 12.9 years. CRC incidence rates per 10 000 person-years of observation were 20.0 (95% CI, 15.3-24.7; n = 70) for advanced adenoma, 9.1 (95% CI, 6.7-11.5; n = 55) for nonadvanced adenoma, and 7.5 (95% CI, 5.8-9.7; n = 71) for no adenoma. Participants with advanced adenoma were significantly more likely to develop CRC compared with participants with no adenoma (rate ratio RR, 2.7 95% CI, 1.9-3.7; P < .001). There was no significant difference in CRC risk between participants with nonadvanced adenoma compared with no adenoma (RR, 1.2 95% CI, 0.8-1.7; P = .30). Compared with participants with no adenoma, those with advanced adenoma were at significantly increased risk of CRC death (RR, 2.6 95% CI, 1.2-5.7, P = .01), but mortality risk in participants with nonadvanced adenoma was not significantly different (RR, 1.2 95% CI, 0.5-2.7, P = .68). CONCLUSIONS AND RELEVANCE: Over a median of 13 years of follow-up, participants with an advanced adenoma at diagnostic colonoscopy prompted by a positive flexible sigmoidoscopy result were at significantly increased risk of developing colorectal cancer compared with those with no adenoma. Identification of nonadvanced adenoma may not be associated with increased colorectal cancer risk. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00002540
Colonoscopy examination does not always detect colorectal cancer (CRC)— some patients develop CRC after negative findings from an examination. When this occurs before the next recommended ...examination, it is called interval cancer. From a colonoscopy quality assurance perspective, that term is too restrictive, so the term post-colonoscopy colorectal cancer (PCCRC) was created in 2010. However, PCCRC definitions and methods for calculating rates vary among studies, making it impossible to compare results. We aimed to standardize the terminology, identification, analysis, and reporting of PCCRCs and CRCs detected after other whole-colon imaging evaluations (post-imaging colorectal cancers PICRCs).
A 20-member international team of gastroenterologists, pathologists, and epidemiologists; a radiologist; and a non-medical professional met to formulate a series of recommendations, standardize definitions and categories (to align with interval cancer terminology), develop an algorithm to determine most-plausible etiologies, and develop standardized methodology to calculate rates of PCCRC and PICRC. The team followed the Appraisal of Guidelines for Research and Evaluation II tool. A literature review provided 401 articles to support proposed statements; evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The statements were voted on anonymously by team members, using a modified Delphi approach.
The team produced 21 statements that provide comprehensive guidance on PCCRCs and PICRCs. The statements present standardized definitions and terms, as well as methods for qualitative review, determination of etiology, calculation of PCCRC rates, and non-colonoscopic imaging of the colon.
A 20-member international team has provided standardized methods for analysis of etiologies of PCCRCs and PICRCs and defines its use as a quality indicator. The team provides recommendations for clinicians, organizations, researchers, policy makers, and patients.
Colorectal cancer (CRC) ranks third among the most commonly diagnosed cancers worldwide, with wide geographical variation in incidence and mortality across the world. Despite proof that screening can ...decrease CRC incidence and mortality, CRC screening is only offered to a small proportion of the target population worldwide. Throughout the world there are widespread differences in CRC screening implementation status and strategy. Differences can be attributed to geographical variation in CRC incidence, economic resources, healthcare structure and infrastructure to support screening such as the ability to identify the target population at risk and cancer registry availability. This review highlights issues to consider when implementing a CRC screening programme and gives a worldwide overview of CRC burden and the current status of screening programmes, with focus on international differences.
Guidelines for initiating colorectal cancer (CRC) screening are based on family history but do not consider lifestyle, environmental, or genetic risk factors. We developed models to determine risk of ...CRC, based on lifestyle and environmental factors and genetic variants, and to identify an optimal age to begin screening.
We collected data from 9748 CRC cases and 10,590 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colorectal Transdisciplinary study, from 1992 through 2005. Half of the participants were used to develop the risk determination model and the other half were used to evaluate the discriminatory accuracy (validation set). Models of CRC risk were created based on family history, 19 lifestyle and environmental factors (E-score), and 63 CRC-associated single-nucleotide polymorphisms identified in genome-wide association studies (G-score). We evaluated the discriminatory accuracy of the models by calculating area under the receiver operating characteristic curve values, adjusting for study, age, and endoscopy history for the validation set. We used the models to project the 10-year absolute risk of CRC for a given risk profile and recommend ages to begin screening in comparison to CRC risk for an average individual at 50 years of age, using external population incidence rates for non-Hispanic whites from the Surveillance, Epidemiology, and End Results program registry.
In our models, E-score and G-score each determined risk of CRC with greater accuracy than family history. A model that combined both scores and family history estimated CRC risk with an area under the receiver operating characteristic curve value of 0.63 (95% confidence interval, 0.62–0.64) for men and 0.62 (95% confidence interval, 0.61–0.63) for women; area under the receiver operating characteristic curve values based on only family history ranged from 0.53 to 0.54 and those based only E-score or G-score ranged from 0.59 to 0.60. Although screening is recommended to begin at age 50 years for individuals with no family history of CRC, starting ages calculated based on combined E-score and G-score differed by 12 years for men and 14 for women, for individuals with the highest vs the lowest 10% of risk.
We used data from 2 large international consortia to develop CRC risk calculation models that included genetic and environmental factors along with family history. These determine risk of CRC and starting ages for screening with greater accuracy than the family history only model, which is based on the current screening guideline. These scoring systems might serve as a first step toward developing individualized CRC prevention strategies.
Display omitted
Myeloid derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that accumulate in circulation of cancer patients and at tumor sites where they suppress anti-tumor ...immunity. We previously reported that in a colon cancer prevention trial of a MUC1 vaccine tested in individuals at increased risk for colon cancer, those who did not mount immune response to the vaccine had higher pre-vaccination levels of circulating MDSC compared to those who did. We also reported that individuals with pancreatic premalignancy, Intraductal Papillary Mucinous Neoplasm (IPMN), had increased circulating levels of MDSC that inversely correlated with spontaneous antibody responses against the pancreatic tumor associated antigen MUC1, abnormally expressed on IPMN. Accumulation of MDSC in cancer and their immunosuppressive role had been well established but their presence in premalignancy was unexpected. In this study we compared MDSC in premalignancy with those in cancer with the hypothesis that there might be differences in the composition of various MDSC subpopulations and their immunosuppressive functions due to different lengths of exposure to disease and/or different tissue microenvironments. In cohorts of patients with premalignant polyps, colon cancer, premalignant IPMN, and pancreatic cancer, we confirmed higher levels of MDSC in premalignancy compared to healthy controls, higher levels of MDSC in cancer compared to premalignancy, but no difference in their subpopulation composition or immunosuppressive capacity. We show that levels of MDSC in premalignancy correlate negatively
with spontaneous MUC1-specific antibody responses and
with polyclonal T cell proliferation and IFN-γ secretion.
PDF
