Defining and Applying Locally Relevant Benchmarks for the Adenoma Detection Rate.

INTRODUCTION: The adenoma detection rate (ADR) is the best validated colonoscopy performance quality indicator. The ASGE/ACG Task Force on Colonoscopy Quality set an ADR benchmark of ≥25% in a mixed male/female population. We propose a novel means for defining locally relevant ADR benchmarks using data from the population of interest and for applying ADR benchmarks using 95% confidence intervals (CIs) of an endoscopist's ADR. We further propose that ADR benchmarks should be raised to reflect what can be achieved by high-performing endoscopists. METHODS: We used endoscopists' performance in a baseline year to develop and apply benchmarks in an assessment year. We defined assessment year benchmarks (Minimally Acceptable, Standard of Care, and Aspirational) based on the average ADR of performance groups defined by baseline year ADR quartiles. We demonstrated the use of these benchmarks in endoscopists performing screening colonoscopies by determining if the upper bound of the 95% CI of the endoscopist's ADR included the ADR benchmark. RESULTS: The study included 8,492 colonoscopies (mean ADR 29%) in 2014 and 5,193 colonoscopies (mean ADR 32%) in 2015, completed at a regional screening center in Calgary, Canada. The Minimally Acceptable, Standard of Care, and Aspirational benchmarks for 2015 were 25%, 30%, and 39%, respectively. The 95% CI of the ADR of 1 (3%), 3 (10%), and 12 (39%) endoscopists did not include the benchmark. DISCUSSION: We have proposed methods for defining and applying benchmarks for ADR in average-risk patients that go beyond the "minimally acceptable" threshold currently recommended.

Determinants of changes in physical activity from pre-diagnosis to post-diagnosis in a cohort of prostate cancer survivors.

PURPOSE: Physical activity (PA) has been shown to improve quality of life and survival in cancer survivors; however, a cancer diagnosis may change PA patterns. We examine determinants of changes in meeting the PA guidelines (150 min/week of moderate aerobic PA) before and after a prostate cancer diagnosis. METHODS: Eight hundred and thirty prostate cancer survivors who participated in a population-based case-control study between 1997 and 2000 in Alberta, Canada, enrolled in a prospective cohort study. Past year activity levels were self-reported at diagnosis (pre-diagnosis measure) and again 2 years post-diagnosis. Determinants were collected by questionnaires and medical chart abstractions. Four PA patterns were created: non-exercisers (fail to meet guidelines pre-diagnosis and post-diagnosis), adopters (fail to meet guidelines pre-diagnosis, meet guidelines post-diagnosis), maintainers (meet guidelines pre-diagnosis and post-diagnosis) and relapsers (meet guidelines pre-diagnosis, fail to meet guidelines post-diagnosis). RESULTS: Multinomial logistic regression analyses identified that being a non-exerciser compared to maintainer was associated with being employed, rural location, high PSA, smoking status, not attending support groups and less than average physical quality of life (QoL). Being a relapser compared to maintainer was associated with rural location and lack of friend support. Finally, being a non-exerciser compared to adopter was associated with urinary incontinence, smoking status and less than average physical and mental QoL. CONCLUSIONS: Demographic, health and lifestyle variables are associated with changes in meeting PA guidelines from pre-diagnosis to post-diagnosis in prostate cancer survivors. Programming should be aimed at offering interventions to help inactive survivors adopt PA and active survivors to maintain PA.

Post-diagnosis alcohol intake and prostate cancer survival: A population-based cohort study.

Alcohol consumption has been declared a Group 1 carcinogen by the International Agency for Research on Cancer (IARC) and is a potential risk factor for several types of cancer mortality. However, evidence for an association with prostate cancer survival remains inconsistent. We examined how alcohol consumption post-diagnosis was associated with survival after prostate cancer diagnosis. Men diagnosed with prostate cancer (n = 829) in Alberta, Canada between the years 1997 and 2000 were recruited into a population-based case-control study and then followed for up to 19 years for survival outcomes. Pre- and post-diagnosis alcohol consumption, clinical characteristics and lifestyle factors were collected through in-person interviews shortly after diagnosis and again 2-3 years post-diagnosis. Cox proportional hazards were used to examine how post-diagnosis alcohol consumption was associated with all-cause and prostate cancer-specific mortality (competing risk analysis too), in addition to first recurrence/progression or new primary cancer. Most participants reported drinking alcohol (≥once a month for 6 months) post-diagnosis (n = 589, 71.0%). Exceeding Canadian Cancer Society (CCS) alcohol consumption recommendations (≥2 drinks/day) post-diagnosis was associated with prostate cancer-specific mortality relative to non-drinkers (aHR: 1.82, 95% CI: 1.07-3.10) with borderline evidence of a linear trend. Interestingly, those in the highest quartile of drinks/week pre- and post-diagnosis also had a twofold increase for prostate-specific mortality (aHR: 2.67, 95% CI: 1.28-5.56) while controlling for competing risks. Our results support post-diagnosis alcohol consumption was associated with increased mortality after prostate cancer diagnosis, specifically for prostate cancer-related death. Future studies focused on confirming this burden of disease are warranted.

Patterns and predictors of adherence to colorectal cancer screening recommendations in Alberta's Tomorrow Project participants stratified by risk.

BACKGROUND: Colorectal cancer (CRC) screening is an important modifiable behaviour for cancer control. Regular screening, following recommendations for the type, timing and frequency based on personal CRC risk, contributes to earlier detection and increases likelihood of successful treatment. METHODS: To determine adherence to screening recommendations in a large provincial cohort of adults, participants in Alberta's Tomorrow Project (n = 9641) were stratified based on increasing level of CRC risk: age (Age-only), family history of CRC (FamilyHx), personal history of bowel conditions (PersonalHx), or both (Family/PersonalHx) using self-reported information from questionnaires. Provincial and national guidelines for timing and frequency of screening tests were used to determine if participants were up-to-date based on their CRC risk. Screening status was compared between enrollment (2000-2006) and follow-up (2008) to determine screening pattern over time. RESULTS: The majority of participants (77%) fell into the average risk Age-only strata. Only a third of this strata were up-to-date for screening at baseline, but the proportion increased across the higher risk strata, with > 90% of the highest risk Family/PersonalHx strata up-to-date at baseline. There was also a lower proportion (< 25%) of the Age-only group who were regular screeners over time compared to the higher risk strata, though age, higher income and uptake of other screening tests (e.g. mammography) were associated with a greater likelihood of regular screening in multinomial logistic regression. CONCLUSIONS: The low (< 50%) adherence to regular CRC screening in average and moderate risk strata highlights the need to further explore barriers to uptake of screening across different risk profiles.

The association between recreational physical activity, sedentary time, and colorectal polyps in a population screened for colorectal cancer.

PURPOSE: Regular recreational moderate to vigorous physical activity (rMVPA) has been previously associated with a reduced risk of colorectal cancer (CRC), however, few studies have examined the association of rMVPA with colorectal polyps, the pre-malignant precursor lesions. The objective of this study was to examine the associations between physical activity and sitting time and polyps at the time of screening. METHODS: We conducted a cross-sectional study of 2496 individuals undergoing screening-related colonoscopy in Calgary, Alberta, Canada. Physical activity and sitting time were characterized using hours of rMVPA, meeting physical activity recommendations and hours of sitting time using self-reported data obtained from the International Physical Activity Questionnaire. Logistic regression models were used to estimate the crude and adjusted odds ratios (OR) for presence of polyps associated with rMVPA and sitting time. RESULTS: Meeting physical activity guidelines of ≥150 min/week was non-significantly associated with a modest decrease in odds of having ≥1 polyp at screening (ORadj = 0.95, 95% CI: 0.80-1.14). In males, threshold effects for sitting time were observed for up to 20 h/week (ORadj per hour sitting = 1.07, 95% CI: 1.01-1.13). In stratified analysis, larger inverse associations were observed between physical activity and the presence of polyps in females, obese individuals, and ever smokers, compared to pooled findings. CONCLUSIONS: In this large CRC screening population, there was a suggestive association between increased rMVPA and reduced prevalence of polyps at screening, particularly among females. Even low amounts of regular sitting time (0-20 h/day) were associated with the presence of polyps, particularly among males. Further research on rMVPA and sitting time is necessary to better inform strategies to reduce the frequency of pre-malignant colorectal lesions.

A quantitative multimodal metabolomic assay for colorectal cancer.

BACKGROUND: Early diagnosis of colorectal cancer (CRC) simplifies treatment and improves treatment outcomes. We previously described a diagnostic metabolomic biomarker derived from semi-quantitative gas chromatography-mass spectrometry. Our objective was to determine whether a quantitative assay of additional metabolomic features, including parts of the lipidome could enhance diagnostic power; and whether there was an advantage to deriving a combined diagnostic signature with a broader metabolomic representation. METHODS: The well-characterized Biocrates P150 kit was used to quantify 163 metabolites in patients with CRC (N = 62), adenoma (N = 31), and age- and gender-matched disease-free controls (N = 81). Metabolites included in the analysis included phosphatidylcholines, sphingomyelins, acylcarnitines, and amino acids. Using a training set of 32 CRC and 21 disease-free controls, a multivariate metabolomic orthogonal partial least squares (OPLS) classifier was developed. An independent set of 28 CRC and 20 matched healthy controls was used for validation. Features characterizing 31 colorectal adenomas from their healthy matched controls were also explored, and a multivariate OPLS classifier for colorectal adenoma could be proposed. RESULTS: The metabolomic profile that distinguished CRC from controls consisted of 48 metabolites (R2Y = 0.83, Q2Y = 0.75, CV-ANOVA p-value < 0.00001). In this quantitative assay, the coefficient of variance for each metabolite was <10%, and this dramatically enhanced the separation of these groups. Independent validation resulted in AUROC of 0.98 (95% CI, 0.93-1.00) and sensitivity and specificity of 93% and 95%. Similarly, we were able to distinguish adenoma from controls (R2Y = 0.30, Q2Y = 0.20, CV-ANOVA p-value = 0.01; internal AUROC = 0.82 (95% CI, 0.72-0.93)). When combined with the previously generated GC-MS signatures for CRC and adenoma, the candidate biomarker performance improved slightly. CONCLUSION: The diagnostic power for metabolomic tests for colorectal neoplasia can be improved by utilizing a multimodal approach and combining metabolites from diverse chemical classes. In addition, quantification of metabolites enhances separation of disease-specific metabolomic profiles. Our future efforts will be focused on developing a quantitative assay for the metabolites comprising the optimal diagnostic biomarker.

Anthropometric measurements and survival after a prostate cancer diagnosis.

BACKGROUND: Evidence regarding the role of anthropometrics in prostate cancer survival is inconsistent. We examined the associations between anthropometric measures and survival outcomes. METHODS: Men diagnosed with prostate cancer (n=987) were recruited into a population-based case-control study between 1997 and 2000 then a prospective cohort study between 2000 and 2002 where anthropometric measurements (weight, height, body mass index, waist circumference, waist-hip ratio) were taken and participants were followed up to 19 years for survival outcomes. Cox proportional hazards were used to examine these associations. RESULTS: Survival analyses suggested no clear pattern of associations between post-diagnosis anthropometric measurements and all-cause mortality, prostate-specific mortality, first recurrence/progression or new primary cancer. CONCLUSIONS: We did not find a significant trend relating anthropometrics to survival outcomes after prostate cancer diagnosis. Continued assessment of objective measurements of body composition over the life-course is warranted to determine true associations between anthropometrics and survival after prostate cancer.

Intake of dietary fibre and lifetime non-steroidal anti-inflammatory drug (NSAID) use and the incidence of colorectal polyps in a population screened for colorectal cancer.

BACKGROUND: There is suggestive evidence that increased intake of dietary fibre and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are generally associated with decreased colorectal cancer risk. However, the effects on precursors of colorectal cancer, such as adenomatous polyps, are mixed. We present the associations between dietary fibre intake and NSAID use on the presence and type of colorectal polyps in a screening population. METHODS: A cross-sectional study of 2548 individuals undergoing colonoscopy at the Forzani & MacPhail Colon Cancer Screening Centre (Calgary, Canada) was conducted. Dietary fibre intake and NSAID use were assessed using the Diet History Questionnaire I or II and the Health and Lifestyle Questionnaire. Colorectal outcomes were documented as a polyp or high-risk adenomatous polyp (HRAP; villous histology, high-grade dysplasia, ≥10 mm or ≥3 adenomas). Crude and ORs and 95% CIs were estimated using unconditional logistic regression. RESULTS: There were 1450 negative colonoscopies and 1098 patients with polyps, of which 189 patients had HRAPs. Total dietary fibre intake was associated with a decreased presence of HRAPs (OR=0.50, 95% CI: 0.29 to 0.86) when comparing the highest to lowest quartiles and was observed with both soluble (OR=0.51, 95% CI: 0.30 to 0.88) and insoluble (OR=0.51, 95% CI: 0.30 to 0.86) fibres. Ever use of NSAIDs was also inversely associated with HRAPs (OR=0.65, 95% CI: 0.47 to 0.89), observed with monthly (OR=0.60, 95% CI: 0.37 to 0.95) and daily (OR=0.53, 95% CI: 0.32 to 0.86) use. CONCLUSIONS: Dietary fibre intake and NSAID use were associated with a decreased risk of having a HRAP at screening.

Performance and Cost-Effectiveness of Computed Tomography Lung Cancer Screening Scenarios in a Population-Based Setting: A Microsimulation Modeling Analysis in Ontario, Canada.

BACKGROUND: The National Lung Screening Trial (NLST) results indicate that computed tomography (CT) lung cancer screening for current and former smokers with three annual screens can be cost-effective in a trial setting. However, the cost-effectiveness in a population-based setting with >3 screening rounds is uncertain. Therefore, the objective of this study was to estimate the cost-effectiveness of lung cancer screening in a population-based setting in Ontario, Canada, and evaluate the effects of screening eligibility criteria. METHODS AND FINDINGS: This study used microsimulation modeling informed by various data sources, including the Ontario Health Insurance Plan (OHIP), Ontario Cancer Registry, smoking behavior surveys, and the NLST. Persons, born between 1940 and 1969, were examined from a third-party health care payer perspective across a lifetime horizon. Starting in 2015, 576 CT screening scenarios were examined, varying by age to start and end screening, smoking eligibility criteria, and screening interval. Among the examined outcome measures were lung cancer deaths averted, life-years gained, percentage ever screened, costs (in 2015 Canadian dollars), and overdiagnosis. The results of the base-case analysis indicated that annual screening was more cost-effective than biennial screening. Scenarios with eligibility criteria that required as few as 20 pack-years were dominated by scenarios that required higher numbers of accumulated pack-years. In general, scenarios that applied stringent smoking eligibility criteria (i.e., requiring higher levels of accumulated smoking exposure) were more cost-effective than scenarios with less stringent smoking eligibility criteria, with modest differences in life-years gained. Annual screening between ages 55-75 for persons who smoked ≥40 pack-years and who currently smoke or quit ≤10 y ago yielded an incremental cost-effectiveness ratio of $41,136 Canadian dollars ($33,825 in May 1, 2015, United States dollars) per life-year gained (compared to annual screening between ages 60-75 for persons who smoked ≥40 pack-years and who currently smoke or quit ≤10 y ago), which was considered optimal at a cost-effectiveness threshold of $50,000 Canadian dollars ($41,114 May 1, 2015, US dollars). If 50% lower or higher attributable costs were assumed, the incremental cost-effectiveness ratio of this scenario was estimated to be $38,240 ($31,444 May 1, 2015, US dollars) or $48,525 ($39,901 May 1, 2015, US dollars), respectively. If 50% lower or higher costs for CT examinations were assumed, the incremental cost-effectiveness ratio of this scenario was estimated to be $28,630 ($23,542 May 1, 2015, US dollars) or $73,507 ($60,443 May 1, 2015, US dollars), respectively. This scenario would screen 9.56% (499,261 individuals) of the total population (ever- and never-smokers) at least once, which would require 4,788,523 CT examinations, and reduce lung cancer mortality in the total population by 9.05% (preventing 13,108 lung cancer deaths), while 12.53% of screen-detected cancers would be overdiagnosed (4,282 overdiagnosed cases). Sensitivity analyses indicated that the overall results were most sensitive to variations in CT examination costs. Quality of life was not incorporated in the analyses, and assumptions for follow-up procedures were based on data from the NLST, which may not be generalizable to a population-based setting. CONCLUSIONS: Lung cancer screening with stringent smoking eligibility criteria can be cost-effective in a population-based setting.

Alberta's Tomorrow Project: adherence to cancer prevention recommendations pertaining to diet, physical activity and body size.

OBJECTIVE: To explore cross-sectional adherence to cancer prevention recommendations by adults enrolled in a prospective cohort in Alberta, Canada. DESIGN: Questionnaire data were used to construct a composite cancer prevention adherence score for each participant, based on selected personal recommendations published by the World Cancer Research Fund/American Institute for Cancer Research (2007). Data were self-reported on health and lifestyle, past-year physical activity and past-year FFQ. The scores accounted for physical activity, dietary supplement use, body size, and intakes of alcohol, fruit, vegetables and red meat. Tobacco exposure was also included. Scores ranged from 0 (least adherent) to 7 (most adherent). SETTING: Alberta's Tomorrow Project; a research platform based on a prospective cohort. SUBJECTS: Adult men and women (n 24 988) aged 35-69 years recruited by random digit dialling and enrolled in Alberta's Tomorrow Project between 2001 and 2009. RESULTS: Of the cohort, 14 % achieved adherence scores ≥5 and 60 % had scores ≤3. Overall adherence scores were higher in women (mean (sd): 3·4 (1·1)) than in men (3·0 (1·2)). The extent of overall adherence was also associated with level of education, employment status, annual household income, personal history of chronic disease, family history of chronic disease and age. CONCLUSIONS: Reported adherence to selected personal recommendations for cancer prevention was low in this cohort of adults. In the short to medium term, these results suggest that more work is required to identify behaviours to target with cancer prevention strategies at a population level. Future work will explore the associations between adherence scores and cancer risk in this cohort.

Identification and prediction of health-related quality of life trajectories after a prostate cancer diagnosis.

The aim of our study was to identify physical and mental health-related quality of life (HRQoL) trajectories after a prostate cancer diagnosis and systematically characterize trajectories by behaviours and prognostic factors. Prostate cancer survivors (n = 817) diagnosed between 1997 and 2000 were recruited between 2000 and 2002 into a prospective repeated measurements study. Behavioural/prognostic data were collected through in-person interviews and questionnaires. HRQoL was collected at three post-diagnosis time-points, approximately 2 years apart using the Short Form (SF)-36 validated questionnaire. To identify physical and mental HRQoL trajectories, group-based trajectory modelling was undertaken. Differences between groups were evaluated by assessing influential dropouts (mortality/poor health), behavioural/prognostic factors at diagnosis or during the follow-up. Three trajectories of physical HRQoL were identified including: average-maintaining HRQoL (32.2%), low-declining HRQoL (40.5%) and very low-maintaining HRQoL (27.3%). In addition, three trajectories for mental HRQoL were identified: average-increasing HRQoL (66.5%), above average-declining HRQoL (19.7%) and low-increasing HRQoL (13.8%). In both physical and mental HRQoL, dropout from mortality/poor health differed between trajectories, thus confirming HRQoL and mortality were related. Furthermore, increased Charlson comorbidity index score was consistently associated with physical and mental HRQoL group membership relative to average maintaining groups, while behaviours such as time-varying physical activity was associated with physical HRQoL trajectories but not mental HRQoL trajectories. It was possible to define three trajectories of physical and mental HRQoL after prostate cancer. These data provide insights regarding means for identifying subgroups of prostate cancer survivors with lower or declining HRQoL after diagnosis whom could be targeted for interventions aimed at improving HRQoL.

Associations of Postdiagnosis Physical Activity and Change from Prediagnosis Physical Activity with Quality of Life in Prostate Cancer Survivors.

BACKGROUND: This prospective study examined the associations between postdiagnosis physical activity and change from prediagnosis physical activity with quality of life (QoL) in prostate cancer survivors. METHODS: Prostate cancer survivors (N = 830) who participated in a case-control study with invasive stage ≥II disease were followed up to 2007 to capture QoL outcomes. At baseline and three time points postdiagnosis (2000-2007), interviews/questionnaires were used to collect data on physical activity, general QoL measured by the SF-36, and other treatment/lifestyle factors. Multivariable linear regression was used to test the relation between postdiagnosis physical activity and QoL as well as the change in physical activity over the diagnostic period and QoL. RESULTS: Both total and recreational physical activities were positively associated with physical QoL. Furthermore, when comparing changes in physical activity levels from pre- to postdiagnosis, men who consistently met physical activity guidelines had significantly higher physical [ß = 6.01; 95% confidence interval (CI), 4.15-7.86] and mental (ß = 2.32; 95% CI, 0.29-4.34) QoL scores compared with those who did not meet guidelines pre- or postdiagnosis. Furthermore, those who adopted and met guidelines had increased QoL, whereas those who relapsed experienced decreased QoL. CONCLUSIONS: Postdiagnosis recreational physical activity is associated with better physical QoL in prostate cancer survivors. Moreover, prostate cancer survivors who maintain or adopt physical activity after diagnosis report substantially higher QoL than men who never exercised or stopped exercising after diagnosis. IMPACT: Future intervention studies should focus on achieving and maintaining adherence to physical activity guidelines postdiagnosis in prostate cancer survivors. Cancer Epidemiol Biomarkers Prev; 26(2); 179-87. ©2016 AACR.

Defining Benchmarks for Adenoma Detection Rate and Adenomas Per Colonoscopy in Patients Undergoing Colonoscopy Due to a Positive Fecal Immunochemical Test.

OBJECTIVES: Although there is an accepted benchmark for adenoma detection rate (ADR) in average risk screening colonoscopy, a benchmark for ADR or the associated quality indicator, adenomas per colonoscopy (APC), for colonoscopies performed for a positive fecal immunochemical test (FIT+) has not been established. The purpose of this study was to propose methods for establishing a benchmark ADR and APC for FIT+ patients. METHODS: In this historical cohort study, we included 15,329 patients aged 50-74 years who underwent a colonoscopy at Alberta Health Services' Colon Cancer Screening Centre, Calgary, Canada, from 1 January 2014 to 30 June 2015 for either investigation of a positive FIT or average risk screening. Using meta-regression, we estimated for FIT+ patients the ADR and APC that corresponded to (Method #1: minimally acceptable) an ADR of 25% in average risk individuals, (Method #2: standard of care) the average ADR or APC in all FIT+ patients, and (Method #3: aspirational) the average FIT+ ADR or APC in colonoscopies performed by endoscopists with an ADR of ≥35% in average risk patients. RESULTS: At least one adenoma was detected in 30% of average risk patients and 58% of FIT+ patients. The calculated benchmark FIT+ ADRs for the three methods were 55, 60, and 65%, respectively. The calculated benchmarks for FIT+ APC were 1.2, 1.4, and 1.7, respectively. To account for expected random variation in individual endoscopists' ADR or APC, we propose using the upper bound of the 95% confidence interval of an endoscopist's ADR or APC to determine if they fall below a given benchmark. CONCLUSIONS: We have proposed methods of defining benchmarks for ADR and APC in FIT+ patients that go beyond the current "minimally acceptable" threshold currently recommended in average risk patients. These new thresholds represent results obtained by all peers and by a group of expert adenoma detectors defined in an independent patient cohort (average risk). Because the true adenoma burden in FIT+ patients could vary based on factors such as the threshold used to define a positive FIT, screening programs or endoscopy units may need to calculate their own benchmarks using local data.

Design, methods and demographics from phase I of Alberta's Tomorrow Project cohort: a prospective cohort profile.

BACKGROUND: Prospective cohorts have the potential to support multifactorial, health-related research, particularly if they are drawn from the general population, incorporate active and passive follow-up and permission is obtained to allow access by researchers to data repositories. This paper describes Phase I of the Alberta's Tomorrow Project cohort, a broad-based research platform designed to support investigations into factors that influence cancer and chronic disease risk. METHODS: Adults aged 35-69 years living in Alberta, Canada, with no previous cancer diagnosis other than nonmelanoma skin cancer were recruited to the project by telephone-based random digit dialling. Participants were enrolled if they returned a Health and Lifestyle Questionnaire. Past year diet and physical activity questionnaires were mailed 3 months after enrolment. Consent was sought for active follow-up and linkage with administrative databases. Depending on enrolment date, participants were invited to complete up to 2 follow-up questionnaires (2004 and 2008). RESULTS: Between 2001 and 2009, 31 072 (39% men) participants (mean age 50.2 [± 9.2] yr) were enrolled and 99% consented to linkage with administrative databases. Participants reported a wide range of educational attainment and household income. Compared with provincial surveillance data from the Canadian Community Health Survey, Alberta's Tomorrow Project participants had higher body mass index, lower prevalence of smoking and similar distribution of chronic health conditions. Follow-up questionnaires were completed by 83% and 72% of participants in 2004 and 2008, respectively. Robust quality control measures resulted in low frequencies of missing data. INTERPRETATION: Alberta's Tomorrow Project provides a robust platform, based on a prospective cohort design, to support research into risk factors for cancer and chronic disease.

A validated metabolomic signature for colorectal cancer: exploration of the clinical value of metabolomics.

BACKGROUND: Timely diagnosis and classification of colorectal cancer (CRC) are hindered by unsatisfactory clinical assays. Our aim was to construct a blood-based biomarker series using a single assay, suitable for CRC detection, prognostication and staging. METHODS: Serum metabolomic profiles of adenoma (N=31), various stages of CRC (N=320) and healthy matched controls (N=254) were analysed by gas chromatography-mass spectrometry (GC-MS). A diagnostic model for CRC was derived by orthogonal partial least squares-discriminant analysis (OPLS-DA) on a training set, and then validated on an independent data set. Metabolomic models suitable for identifying adenoma, poor prognosis stage II CRC and discriminating various stages were generated. RESULTS: A diagnostic signature for CRC with remarkable multivariate performance (R(2)Y=0.46, Q(2)Y=0.39) was constructed, and then validated (sensitivity 85%; specificity 86%). Area under the receiver-operating characteristic curve was 0.91 (95% CI, 0.87-0.96). Adenomas were also detectable (R(2)Y=0.35, Q(2)Y=0.26, internal AUROC=0.81, 95% CI, 0.70-0.92). Also of particular interest, we identified models that stratified stage II by prognosis, and classified cases by stage. CONCLUSIONS: Using a single assay system, a suite of CRC biomarkers based on circulating metabolites enables early detection, prognostication and preliminary staging information. External population-based studies are required to evaluate the repeatability of our findings and to assess the clinical benefits of these biomarkers.

Physical Activity and Survival After Prostate Cancer.

BACKGROUND: Despite the high global prevalence of prostate cancer (PCa), few epidemiologic studies have assessed physical activity in relation to PCa survival. OBJECTIVE: To evaluate different types, intensities, and timing of physical activity relative to PCa survival. DESIGN, SETTING, AND PARTICIPANTS: A prospective study was conducted in Alberta, Canada, in a cohort of 830 stage II-IV incident PCa cases diagnosed between 1997 and 2000 with follow-up to 2014 (up to 17 yr). Prediagnosis lifetime activity was self-reported at diagnosis. Postdiagnosis activity was self-reported up to three times during follow-up. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox proportional hazards models related physical activity to all-cause and PCa-specific deaths and to first recurrence/progression of PCa. RESULTS AND LIMITATIONS: A total of 458 deaths, 170 PCa-specific deaths, and, after first follow-up, 239 first recurrences/progressions occurred. Postdiagnosis total activity (>119 vs ≤42 metabolic equivalent [MET]-hours/week per year) was associated with a significantly lower all-cause mortality risk (hazard ratio [HR]: 0.58; 95% confidence interval [CI], 0.42-0.79; p value for trend <0.01). Postdiagnosis recreational activity (>26 vs ≤4 MET-hours/week per year) was associated with a significantly lower PCa-specific mortality risk (HR: 0.56; 95% CI, 0.35-0.90; p value for trend = 0.01). Sustained recreational activity before and after diagnosis (>18-20 vs <7-8 MET-hours/week per year) was associated with a lower risk of all-cause mortality (HR: 0.66; 95% CI, 0.49-0.88). Limitations included generalisability to healthier cases and an observational study design. CONCLUSIONS: These findings support emerging recommendations to increase physical activity after the diagnosis of PCa and would inform a future exercise intervention trial examining PCa outcomes. PATIENT SUMMARY: In a 17-yr prostate cancer (PCa) survival study, men who survived at least 2 yr who were more physically active postdiagnosis or performed more recreational physical activity before and after diagnosis survived longer. Recreational physical activity after diagnosis was associated with a lower risk of PCa death.

Evaluation of a clinical risk index for advanced colorectal neoplasia among a North American population of screening age.

BACKGROUND: A clinical risk index employing age, sex, family history of colorectal cancer (CRC), smoking history and body mass index (BMI) may be useful for prioritizing screening with colonoscopy. The aim of this study was to conduct an external evaluation of a previously published risk index for advanced neoplasia (AN) in a large, well-characterized cohort. METHODS: Five thousand one hundred thirty-seven asymptomatic persons aged 50 to 74 (54.9 % women) with a mean age (SD) of 58.3 (6.2) years were recruited for the study from a teaching hospital and colorectal cancer screening centre between 2003 and 2011. All participants underwent a complete screening colonoscopy and removal of all polyps. AN was defined as cancer or a tubular adenoma, traditional serrated adenoma (TSA), or sessile serrated adenoma (SSA) with villous characteristics (≥25% villous component), and/or high-grade dysplasia and/or diameter ≥10 mm. Risk scores for each participant were summed to derive an overall score (0-8). The c-statistic was used to measure discriminating ability of the risk index. RESULTS: The prevalence of AN in the study cohort was 6.8 %. The likelihood of detecting AN increased from 3.6 to 13.1 % for those with a risk score of 1 to 6 respectively. The c-statistic for the multivariable logistic model in our cohort was 0.64 (95 % CI = 0.61-067) indicating modest overlap between risk scores. CONCLUSIONS: The risk index for AN using age, sex, family history, smoking history and BMI was found to be of limited discriminating ability upon external validation. The index requires further refinement to better predict AN in average risk persons of screening age.

The association of colonoscopy quality indicators with the detection of screen-relevant lesions, adverse events, and postcolonoscopy cancers in an asymptomatic Canadian colorectal cancer screening population.

BACKGROUND: Although several quality indicators of colonoscopy have been defined, quality assurance activities should be directed at the measurement of quality indicators that are predictive of key screening colonoscopy outcomes. OBJECTIVE: The goal of this study was to examine the association among established quality indicators and the detection of screen-relevant lesions (SRLs), adverse events, and postcolonoscopy cancers. DESIGN: Historical cohort study. SETTING: Canadian colorectal cancer screening center. PATIENTS: A total of 18,456 asymptomatic men and women ages 40 to 74, at either average risk or increased risk for colorectal cancer because of a family history, who underwent a screening colonoscopy from 2008 to 2010. MAIN OUTCOME MEASUREMENTS: Using univariate and multivariate analyses, we explored the association among procedural quality indicators and 3 colonoscopy outcomes: detection of SRLs, adverse events, and postcolonoscopy cancers. RESULTS: The crude rates of SRLs, adverse events, and postcolonoscopy cancers were 240, 6.44, and .54 per 1000 colonoscopies, respectively. Several indicators, including endoscopist withdrawal time (OR, 1.3; 95% CI, 1.2-1.4) and cecal intubation rate (OR, 13.9; 95% CI, 1.9-96.9), were associated with the detection of SRLs. No quality indicator was associated with the risk of adverse events. Endoscopist average withdrawal time over 6 minutes (OR, .12; 95% CI, .002-.85) and SRL detection rate over 20% (OR, .17; 95% CI, .03-.74) were associated with a reduced risk of postcolonoscopy cancers. LIMITATIONS: Single-center study. CONCLUSION: Quality assurance programs should prioritize the measurement of endoscopist average withdrawal time and adenoma (SRL) detection rate.

Acceptability and yield of birth-cohort screening for hepatitis C virus in a Canadian population being screened for colorectal cancer: a cross-sectional study.

BACKGROUND: Screening for hepatitis C virus (HCV) is recommended in patients born between 1945 and 1965 ("baby boomers") in the United States. Because these patients are often screened for colorectal cancer, dual screening for HCV may enhance case identification. Our objectives were to assess the acceptability and yield of screening for HCV among patients undergoing screening for colorectal cancer. METHODS: Patients referred for a colonoscopy to screen for colorectal cancer completed an anonymous survey regarding the acceptability of screening for HCV, risk factors and prior testing. The impacts of demographics and risk factors for HCV on willingness to be screened were determined using logistic regression, and the stored sera of 483 patients who had undergone screening for colorectal cancer between February 2011 and August 2012 were tested for HCV antibodies. RESULTS: Among 1012 survey respondents (median age 56 yr; 911 [90.0%] were baby boomers, 880 [87.0%] were white and 223 [22.0%] were born outside Canada), 123 patients (12.2%) reported prior testing for HCV. HCV was previously diagnosed in 9 of these patients (0.9%, representing 1.0% of the patients who were baby boomers): 5 (55.6% of those diagnosed) reported risk factors. Excluding patients diagnosed with HCV, 903 (90.0%) respondents indicated that they would consent to testing of blood or saliva for HCV. After adjusting for age, sex and status of immigration, patients who were white (odds ratio [OR] 3.38, 95% confidence interval [CI] 1.81-6.32) and patients with risk factors (> 1 v. 0: OR 3.67, 95% CI 1.12-12.02) had a greater acceptance of screening. Among 483 patients screened for colorectal cancer, 3 were anti-HCV positive (0.6%, 95% CI 0.1%-1.8%), representing 0.8% (95% CI 0.2%-2.4%) of the patients who were baby boomers. INTERPRETATION: Acceptance of screening for HCV is high among patients undergoing screening for colorectal cancer in the Calgary area. However, the low prevalence of HCV suggests that the cost-effectiveness of birth-cohort screening in this population warrants evaluation.