Colorectal cancer: A health and economic problem.

Colorectal Cancer (CRC) is the third most commonly diagnosed form of cancer and accounts for approximately 1.9 million cancer cases each year (10% of all new cancer cases globally). Incidence strongly increases with age and has been traditionally highest in Western, affluent countries, but it is rapidly increasing in many less developed countries and in younger generations in both developed and developing countries. With demographic aging, CRC will pose a rapidly increasing challenge for many societies, which underlines the need for major efforts on primary and secondary prevention. A number of effective screening options are available, and implementation of well-organized screening programs could have a major impact on lowering the future burden of the disease.

Assessment of Body Mass Index, Polygenic Risk Score, and Development of Colorectal Cancer.

Importance: Excess weight, the prevalence of which is high and increasing in many countries, is linked to multiple adverse health outcomes, including increased colorectal cancer (CRC) risk. Better communication of health risks associated with excess weight might support efforts of prevention. Objective: To evaluate the individual and joint associations of body mass index (BMI) and polygenic risk with CRC, to assess potential interactions among them, and to quantify by how much increased polygenic risk for CRC can be offset by having a BMI within reference range. Design, Setting, and Participants: This population-based case-control study was conducted in the Rhine-Neckar region of southwest Germany, with recruitment from 2003 to 2017. Participants with both risk factor and genetic information were included for analysis. Data analysis was conducted from December 8, 2021, to February 17, 2022. Exposures: BMI was calculated as self-reported weight in kilograms approximately 10 years before diagnosis or interview and current height in meters squared. A polygenic risk score (PRS) was built based on 140 CRC-related risk loci. Main Outcomes and Measures: Individual and joint associations of BMI and PRS with CRC were estimated using multiple logistic regression. Associations of excess weight with CRC were quantified by adjusted odds ratios (aORs) and genetic risk equivalents (GREs), the equivalent outcomes conveyed by defined differences in PRS percentiles. Results: Among 9169 participants (median [IQR] age, 69 [62-76] years; 5589 [61.0%] male participants) included, 5053 had CRC and 4116 did not. BMI of 30 or greater was associated with higher odds of having CRC compared with BMI less than 25 (aOR, 1.71; 95% CI, 1.49-1.97), independent of PRS levels (P for interaction = .45). Participants with BMI of 30 or greater and a PRS in the highest tertile had higher odds of CRC compared with participants with BMI less than 25 and a PRS in the lowest tertile (aOR, 3.82; 95% CI, 3.03-4.82). The estimated association of BMI greater than 30 with CRC risk was equivalent to that of having a 41 (95% CI, 29-53)-percentile higher PRS. BMI of 30 or greater was particularly associated with stage IV CRC (aOR, 2.21; 95% CI, 1.71-2.84). Conclusions and Relevance: These findings suggest that excess weight was associated with CRC regardless of PRS levels. The association of having a BMI within reference range may be similar to that of having a substantially lower polygenic risk for CRC.

Treatment Costs of Colorectal Cancer by Sex and Age: Population-Based Study on Health Insurance Data from Germany.

Objective: Evidence on the cost-effectiveness of screening for colorectal cancer (CRC) in the German general population remains scarce as key input parameters, the costs to treat CRC, are largely unknown. Here, we provide detailed estimates on CRC treatment costs over time. Methods: Using insurance claims data from the Vilua healthcare research database, we included subjects with newly diagnosed CRC and subjects who died of CRC between 2012 and 2016. We assessed annualized CRC-related inpatient, outpatient and medication costs for up to five years after first diagnosis and prior to death, stratified by sex and age. Findings: We identified 1748 and 1117 subjects with follow-up data for at least 1 year after diagnosis and prior to death, respectively. In those newly diagnosed, average costs were highest in the first year after diagnosis (men, EUR 16,375−16,450; women, EUR 10,071−13,250) and dropped steeply in the following years, with no consistent pattern of differences with respect to age. Costs prior to death were substantially higher as compared to the initial phase of care and consistently on a high level even several years before death, peaking in the final year of life, with strong differences by sex and age (men vs. women, <70 years, EUR 34,351 vs. EUR 31,417; ≥70 years, EUR 14,463 vs. EUR 9930). Conclusion: Once clinically manifest, CRC causes substantial treatment costs over time, particularly in the palliative care setting. Strong differences in treatment costs by sex and age warrant further investigation.

Strongly Divergent Impact of Adherence Patterns on Efficacy of Colorectal Cancer Screening: The Need to Refine Adherence Statistics.

INTRODUCTION: The performance of colorectal cancer (CRC) screening programs depends on the adherence to screening offers. However, identical adherence levels may result from varying patterns of the population's screening behavior. We quantified the effects of different adherence patterns on the long-term performance of CRC screening for annual fecal immunochemical testing and screening colonoscopy at 10-year intervals. METHODS: Using a multistate Markov model, we simulated scenarios where, while at the same overall adherence level, a certain proportion of the population adheres to all screening offers (selective adherence) or the entire population uses the screening offers at some point(s) of time, albeit not in the recommended frequency (sporadic adherence). Key outcomes for comparison were the numbers of prevented CRC cases and prevented CRC deaths after 50 simulated years. RESULTS: For screening with annual fecal immunochemical testing at adherence levels of 10%-50%, ratios of prevented CRC cases (CRC deaths) resulting from a sporadic vs a selective pattern ranged from 1.8 to 4.4 (1.9-5.3) for men and from 1.7 to 3.6 (1.8-4.4) for women, i.e., up to 4-5 times more CRC cases and deaths were prevented when the population followed a sporadic instead of a selective adherence pattern. Comparisons of simulated scenarios for screening colonoscopy revealed similar patterns. DISCUSSION: Over a lifelong time frame, large numbers of irregular screening attendees go along with much larger preventive effects than small numbers of perfectly adhering individuals. In clinical practice, efforts to reach as many people as possible at least sporadically should be prioritized over efforts to maximize adherence to repeat screening offers.

Uptake Rates of Novel Therapies and Survival Among Privately Insured Versus Publicly Insured Patients With Colorectal Cancer in Germany.

BACKGROUND: In the era of personalized medicine, cancer care is subject to major changes and innovations. It is unclear, however, to what extent implementation of such innovations and their impact on patient outcomes differ by health insurance type. This study compared provision of treatment and survival outcomes among patients with colorectal cancer (CRC) who had statutory health insurance (SHI) versus private health insurance (PHI) in Germany. METHODS: We analyzed patterns of CRC treatment (surgery, chemotherapy/radiotherapy, and targeted therapy) and survival in a large cohort of patients who were diagnosed with CRC in 2003 through 2014 and were observed for an average of 6 years. Associations of type of health insurance with treatment administration and with overall, CRC-specific, and recurrence-free survival were investigated using multivariable logistic and Cox proportional hazards models, respectively. RESULTS: Of 3,977 patients with CRC, 427 (11%) had PHI. Although type of health insurance was not associated with treatment administration in patients with stage I-III disease, those with stage IV disease with PHI more often received targeted therapy (65% vs 40%; odds ratio, 2.43; 95% CI, 1.20-4.91), with differences decreasing over time because of catch-up of uptake rates in patients with SHI. Median overall survival was longer in patients with PHI than in those with SHI (137.0 vs 114.9 months; P=.010), but survival advantages were explained to a large extent by differences in sociodemographic factors. In patients with stage IV disease, survival advantages of PHI were nonsignificant and were restricted to the early years after diagnosis. CONCLUSIONS: We observed major differences in uptake of targeted therapy between patients with PHI and those with SHI but no differences in patient survival after adjusting for relevant sociodemographic, clinical, and tumor characteristics. Further studies are needed on factors associated with the uptake of therapeutic innovations and their impact on patient survival by health insurance type.

Effects of screening for colorectal cancer: Development, documentation and validation of a multistate Markov model.

Simulation models are a powerful tool to overcome gaps of evidence needed to inform medical decision-making. Here, we present development and application of COSIMO, a Markov-based Colorectal Cancer (CRC) Multi-state Simulation Model to simulate effects of CRC screening, along with a thorough assessment of the model's ability to reproduce real-life outcomes. Firstly, we provide a comprehensive documentation of COSIMO's development, structure and assumptions. Secondly, to assess the model's external validity, we compared model-derived cumulative incidence and prevalences of colorectal neoplasms to (a) results from KolosSal, a study in German screening colonoscopy participants, (b) registry-based estimates of CRC incidence in Germany, and (c) outcome patterns of randomized sigmoidoscopy screening studies. We found that (a) more than 90% of observed prevalences in the KolosSal study were within the 95% confidence intervals of the model-predicted neoplasm prevalences; (b) the 15-year cumulative CRC incidences estimated by simulations for the German population deviated by 0.0% to 0.2% units in men and 0.0% to 0.3% units in women when compared to corresponding registry-derived estimates; and (c) the time course of cumulative CRC incidence and mortality in the modeled intervention group and control group closely resembles the time course reported from sigmoidoscopy screening trials. Overall, COSIMO adequately predicted colorectal neoplasm prevalences and incidences in a German population for up to 25 years, with estimated patterns of the effect of screening colonoscopy resembling those seen in registry data and real-world studies. This suggests that the model may represent a valid tool to assess the comparative effectiveness of CRC screening strategies.

Age-specific sequence of colorectal cancer screening options in Germany: A model-based critical evaluation.

BACKGROUND: The current organized screening program for colorectal cancer in Germany offers both sexes 5 annual fecal immunochemical tests (FITs) between ages 50 and 54 years, followed by a first screening colonoscopy at age 55 years if all of these FITs were negative. We sought to assess the implications of this approach for key parameters of diagnostic performance. METHODS AND FINDINGS: Using a multistate Markov model, we estimated the expected detection rates of advanced neoplasms (advanced adenomas and cancers) and number needed to scope (NNS) to detect 1 advanced neoplasm at a first screening colonoscopy conducted at age 55 after 5 preceding negative FITs and compared them with the corresponding estimates for a first screening colonoscopy at age 55 with no preceding FIT testing. In individuals with 5 consecutive negative FITs undergoing screening colonoscopy at age 55, expected colonoscopy detection rate (NNS) was 3.7% (27) and 0.10% (1,021) for any advanced neoplasm and cancer, respectively, in men, and 2.1% (47) and 0.05% (1,880) for any advanced neoplasm and cancer, respectively, in women. These NNS values for detecting 1 advanced neoplasm are approximately 3-fold higher, and the NNS values for detecting 1 cancer are approximately 8-fold higher, than those for a first screening colonoscopy at age 55 without prior FITs. This study is limited by model simplifying assumptions and uncertainties related to input parameters. CONCLUSIONS: Screening colonoscopy at age 55 after 5 consecutive negative FITs at ages 50-54, as currently offered in the German cancer early detection program, is expected to have very low positive predictive value. Our results may inform efforts to enhance the design of screening programs.

Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers.

Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.

Utilisation of Colorectal Cancer Screening Tests in European Countries by Type of Screening Offer: Results from the European Health Interview Survey.

In the past two decades, an extensive rollout of colorectal cancer (CRC) screening programmes has been initiated in European countries with a large heterogeneity of screening offers. Using data from a population-based cross-sectional survey conducted between 2013 and 2016 in all European Union countries, we analysed the utilisation of faecal tests and colonoscopy among people aged 50-74 years and the factors associated with uptake by type of screening offer. We observed the highest utilisation of either test for countries with fully rolled out organised programmes with faecal tests (ranging from 29.7% in Croatia to 66.7% in the UK) and countries offering both faecal tests and colonoscopy (from 22.7% in Greece to 70.9% in Germany). Utilisation was very low for countries with no programme (from 6.3% in Romania to 30.5% in Norway). Younger age (50-54 years), longer time since last consultation with a doctor and a lifestyle score associated with increased CRC risk were significantly associated with lower test use, a pattern observed across all types of screening offers. Our results suggest that more countries should implement organised programmes with faecal immunochemical tests, in combination with alternative endoscopy offers where resources allow. Furthermore, there is a large potential for increasing screening use in Europe by better reaching the younger eligible individuals, those who have not been to the doctor recently and those at increased risk for CRC.

Association of laparoscopic colectomy versus open colectomy on the long-term health-related quality of life of colon cancer survivors.

BACKGROUND: Laparoscopic colectomy (LC) is a less invasive alternative to open colectomy (OC) in the treatment of stage I-III colon cancer. Research on the long-term (5-year post-diagnosis) health-related quality of life (HRQOL) of LC patients is scarce. Our study aimed to compare the long-term HRQOL and psychological well-being of stage I-III colon cancer survivors treated either with LC or OC. METHODS: This study used a German population-based cohort of patients treated with either LC (n = 86) or OC (n = 980). LC patients were matched to OC patients using a propensity score. At 5-year follow-up, patients completed assessments on HRQOL (EORTC QLQ-C30 and EORTC QLQ-CR29) and psychological well-being (distress and disease/treatment burden). Least square mean scores of HRQOL were derived using linear regression. Proportions of patients with moderate/high distress and disease/treatment burden were compared with Chi-square tests. RESULTS: In total, 81 LC patients were matched to 156 OC patients. Generally, LC patients had HRQOL comparable to OC patients, albeit LC patients reported significantly better body image (87.1 versus 81.0, p = 0.03). Distress levels were generally low and comparable between the two groups, even though LC patients were more likely to experience disease recurrence (16% versus 7%, p = 0.02) than OC patients. OC patients were more likely to feel moderate/high levels of burden associated with the treatment (72% versus 56%, p = 0.01) and the time after treatment completion (43% versus 28%, p = 0.02). CONCLUSION: LC patients reported comparable long-term HRQOL outcomes but higher levels of psychological well-being than OC patients 5 years after diagnosis, even though LC was associated with higher risk of disease recurrence.

Optimal age for screening colonoscopy: a modeling study.

BACKGROUND AND AIMS: Recent guidelines on colorectal cancer (CRC) screening recommend starting screening earlier than before. We performed a simulation study to examine and compare the optimal ages to have once-only screening colonoscopy and repeated colonoscopies. METHODS: A Markov model was set up using data from the German national screening colonoscopy registry to simulate the natural history of the adenoma-carcinoma process. CRC deaths and years of potential life lost (YPLL) for a hypothetical unscreened 50-year-old German population were estimated for a single screening colonoscopy or 2 or 3 screening colonoscopies with 10-year intervals at various ages. RESULTS: One single screening colonoscopy performed between 50 and 65 years of age was expected to reduce CRC death by 49% to 69% and YPLL by 51% to 68%. An inverted U-shaped association was found between screening age and proportion of CRC deaths or YPLL prevented. The optimal age for once-only colonoscopy that yielded the highest reductions in YPLL was around 54 years for men and 56 years for women. Estimates were approximately 6 to 8 years higher when proportions of CRC deaths prevented were examined. For 2 or 3 screening colonoscopies, the optimal starting age fell to around 50 years or even younger for both genders. CONCLUSIONS: Based on the YPLL estimates, in a high CRC incidence and high life expectancy country like Germany, the optimal age for once-only screening colonoscopy is around 55 years and possibly slightly younger for men than for women. When 2 or more screening colonoscopies are offered with 10-year intervals, screening should start at age 50 at the latest or possibly even younger for both genders.

A Web-based survey among adults aged 40-54 years was time effective and yielded stable response patterns.

OBJECTIVE: We want to present information about response patterns obtained by Web-based survey in a large-scale epidemiological study. STUDY DESIGN AND SETTING: Within the RAPS (Risk Adapted Prevention Strategies for colorectal cancer [CRC]) study, we invited 160,000 randomly selected persons aged 40-54 years in three large German cities from 2015 to 2016 to complete a Web-based questionnaire on CRC risk factors and screening (97 items, average time for completion 15 minutes). Invitation letters and up to two reminder letters were sent to each individual. RESULTS: A total of 21.4% of women and 18.0% of men completed the questionnaire. Overall cumulative response rates were 7.5%, 14.3%, and 19.6% after the initial invitation letter, and the first and second reminder, respectively, with prevalence of and associations of key epidemiological parameters (such as family history of cancer, previous colonoscopy, etc.) being remarkably stable across waves of responses. For example, the sex and age distribution of the sample did not change with additional answers gained from additional letters. CONCLUSION: Web-based questionnaires are feasible, cost-effective, and time effective in the setting of large-scale epidemiological studies. Although response patterns were remarkably stable over several rounds of reminders with substantially increasing cumulative response rates, future research should address possibilities to further enhance response rates.

How long does it take until the effects of endoscopic screening on colorectal cancer mortality are fully disclosed?: a Markov model study.

A recent randomized trial has suggested persisting protection from colorectal cancer (CRC) incidence and mortality of a single flexible sigmoidoscopy for up to 17 years and possibly beyond. We performed a simulation study to explore the time course and magnitude of protection provided by screening colonoscopy against CRC death over 25 years. Using data from the German national screening colonoscopy registry, a multistate Markov model was set up based on the adenoma-carcinoma pathway to estimate cumulative CRC mortality when different proportions of the population have a single screening colonoscopy at age 55, or two screening colonoscopies at ages 55 and 65. Cumulative CRC mortality continuously increased with age and reached 2.6 and 1.7% at age 80 in the absence of screening for men and women, respectively. A single colonoscopy at age 55, even with limited uptake, would lead to much lower cumulative mortality (0.7% for men and 0.5% for women at age 80 under 100% uptake). Relative mortality reduction continued to increase over more than 10 years and reached the maximum around 12-13 years after screening. Absolute risk reduction steadily increased throughout follow-up and more than half of the total risk reduction would occur between 15-25 years. A repeat colonoscopy 10 years later further enhanced the effects and cumulative mortality remained at 0.1-0.2% under 100% uptake. Even a single (once-only) screening colonoscopy has the potential to prevent most of CRC mortalities. Protective effects are expected to be long-lasting and to become fully manifest after more than two decades from screening.

Associations of red and processed meat with survival after colorectal cancer and differences according to timing of dietary assessment.

BACKGROUND: Little is known about the prognostic impact of red and processed meat intake or about changes in consumption after a diagnosis of colorectal cancer (CRC). OBJECTIVES: We investigated associations of baseline red and processed meat with survival outcomes and explored changes in intake among CRC survivors 5 y after diagnosis. DESIGN: A total of 3122 patients diagnosed with CRC between 2003 and 2010 were followed for a median of 4.8 y [DACHS (Darmkrebs: Chancen der Verhütung durch Screening) study]. Patients provided information on diet and other factors in standardized questionnaires at baseline and at the 5-y follow-up. Cox proportional hazards regression models were used to estimate HRs and 95% CIs. RESULTS: Among patients with stage I-III CRC, baseline red and processed meat intake was not associated with overall (>1 time/d compared with <1 time/d; HR: 0.85; 95% CI: 0.67, 1.09), CRC-specific (HR: 0.83; 95% CI: 0.61, 1.14), cardiovascular disease-specific (HR: 0.92; 95% CI: 0.51, 1.68), non-CRC-specific (HR: 0.88; 95% CI: 0.59, 1.30), and recurrence-free (HR: 1.03; 95% CI: 0.80, 1.33) survival; results among stage IV patients were comparable. An association with worse overall survival was found among patients with Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated CRC (HR: 1.99; 95% CI: 1.10, 3.56) but not with microsatellite instability or CpG island methylator phenotype (CIMP) positivity. A much lower proportion of survivors reported daily consumption of red and processed meat at the 5-y follow-up than at baseline (concordance rate: 39%; κ-value: 0.10; 95% CI: 0.07, 0.13). CONCLUSIONS: Our findings suggest that baseline red and processed meat intake is not associated with poorer survival among patients with CRC. The potential interaction with KRAS mutation status warrants further evaluation. Major changes in consumption measured at the 5-y follow-up may have had an impact on our survival estimates.

Estimated long-term effects of the initial 6 years of the German screening colonoscopy program.

BACKGROUND: Colorectal cancer is the most common cancer in Germany. Screening colonoscopies have been offered as a primary screening tool in Germany since the end of 2002. OBJECTIVE: To estimate the numbers of clinically manifest colorectal cancers prevented by detection and removal of advanced adenomas in the initial 6 years of the program. DESIGN: Markov model with single-year transitions. SETTING: German screening colonoscopy program. PATIENTS: Participants in the screening colonoscopy program from 2003 to 2008. INTERVENTIONS: Screening colonoscopy with the removal of advanced colorectal neoplasms. MAIN OUTCOME MEASUREMENTS: The expected numbers of incident colorectal cancers prevented by detection and removal of advanced adenomas. RESULTS: An estimated total number of 73,024 cases of colorectal cancer might have developed from the removed advanced adenomas and become clinically manifest between 55 and 84 years of age in the absence of screening colonoscopy. This number exceeds the number of colorectal cancers diagnosed in 2002 by 27%. Among prevented cancers, 8%, 43%, and 49% would have occurred at ages 55 to 64, 65 to 74, and 75 to 84 years (median age 74 years), respectively; 60% and 40% would have occurred among men and women, respectively; and 22%, 32%, 25%, and 20% would have occurred within 1 to 5, 6 to 10, 11 to 15, and 16 to 30 years, respectively, after colonoscopy (median 10 years). LIMITATIONS: Diagnoses of advanced adenomas are based on records from a large number of endoscopists and pathology laboratories. CONCLUSIONS: Despite relatively low screening participation, the German screening colonoscopy program is expected to make a major contribution to the prevention of colorectal cancer, even though most of the impact will only be seen in the longer run.

Assessment of nutritional intake, body mass index and glycemic control in patients with type-2 diabetes from northern Tanzania.

BACKGROUND/AIMS: Little information is available about the nutrition of people with diabetes from Africa. For the treatment and prevention of diabetes by nutrition, we have assessed the major local foods in a baseline study. METHODS: The staple foods and meal frequencies of 53 outpatients with type-2 diabetes were assessed in a 24-hour dietary recall based on a questionnaire at a diabetes clinic in northern Tanzania in November and December 1999. In addition, data on weight and height, casual blood glucose, urinary glucose and diabetes therapy were ascertained. RESULTS: 72% of the patients had a body mass index of > or =25 kg/m(2); 64% of patients had casual blood glucose levels of >7.8 mmol/l, 47% had >11.1 mmol/l, and most of them were treated by sulfonylureas or conventional insulin therapy. The test for urinary glucose highly correlated with the blood glucose values, and was positive in 59% of patients. 36% of the patients had < or =3 meals/day. The foods stated most frequently were stiff porridge, plantains, bread, rice, beef, milk, amaranth leaves, orange and sunflower oil. The main beverages were water, tea and milk. CONCLUSIONS: The baseline data obtained enable more precise dietary assessment and emphasize the need to collect more data on local food consumption in areas where pharmacological diabetes treatment is limited.