Differences between men and women with respect to colorectal cancer mortality despite screening colonoscopy.

BACKGROUND AND AIMS: Women aged 55 to 59 years have a similar prevalence rate and number needed to screen for colorectal adenomas as men at a 10-year younger age. The aim of this study was to determine sex-specific differences in colorectal cancer mortality and estimate the association with adenomas at screening colonoscopy. METHODS: This retrospective study analyzed 323,139 individuals who underwent colonoscopy within a national colorectal cancer screening program in Austria between January 2007 and December 2020. RESULTS: Median patient age was 60 years (interquartile range, 54-67), and the sex distribution in all age groups was nearly identical. Men had significantly higher odds of having an adenoma or serrated polyp, low-risk polyp, high-risk polyp, or colorectal cancer detected at colonoscopy than women (odds ratio [OR] 1.83; 95% confidence interval [CI], 1.80-1.86; OR, 1.46; 95% CI, 1.44-1.49; OR, 1.74; 95% CI, 1.69-1.80; and OR, 1.87; 95% CI, 1.70-2.05, respectively). Strikingly, male sex, when compared with female sex, was associated with an almost 2-fold (hazard ratio, 1.67; 95% CI, 1.05-2.67) increased risk to die from colorectal cancer when an adenoma or serrated polyp was found at the screening colonoscopy and a 4-fold (hazard ratio, 4.14; 95% CI, 2.72-6.3) increased risk when a high-risk polyp was found at the screening colonoscopy. The cumulative incidence for death of colorectal cancer for 60-year-old individuals was 8.5-fold higher in men as compared with women. Markedly, this sex gap narrowed with increasing age, whereas the difference in deaths of other causes remained similar in all age groups. CONCLUSIONS: Our findings strengthen the necessity of sex-specific screening recommendations. Importantly, further prospective studies should focus on sex differences in tumor biology to propose personalized surveillance guidelines.

Polyp characteristics at screening colonoscopy and post-colonoscopy colorectal cancer mortality: a retrospective cohort study.

BACKGROUND AND AIMS: Polyp size and high-grade dysplasia in polyps at screening colonoscopy are considered risk factors for post-colonoscopy colorectal cancer (PCCRC) development and death, which might be averted by surveillance colonoscopy. However, robust evidence backing these risk factors is lacking. We aimed to investigate whether polyp size or dysplasia grade is associated with PCCRC mortality. METHODS: This was a retrospective study including individuals of the Austrian Quality Certificate for Screening Colonoscopy who underwent a colonoscopy between January 2007 and December 2020. We investigated the association of polyp size and dysplasia in polyps with PCCRC mortality according to Cox regression analysis. In addition, whether patients with certain polyp characteristics had similar risk for CRC death compared with the Austrian population was assessed by calculating standardized mortality ratios (SMRs). RESULTS: A total of 316,001 individuals were included. After a median follow-up time of 5.27 years (95% confidence interval [CI], 5.25-5.29), a significant association of polyps 10 to 20 mm (hazard ratio, 4.00; 95% CI, 2.46-6.50; P < .001) as well as high-grade dysplasia (hazard ratio, 6.61; 95% CI, 3.31-13.2; P < .001) with PCCRC death was observed. PCCRC mortality was significantly lower than the expected CRC mortality in the general population in patients with polyps <10 mm and without high-grade dysplasia (SMR, .27; 95% CI, .21-.33; P < .001), which was not observed for patients with polyps ≥10 mm or with high-grade dysplasia (SMR, 2.05; 95% CI, 1.64-2.57; P < .001). CONCLUSIONS: Polyp size ≥10 mm and high-grade dysplasia are associated with PCCRC mortality in screening patients. The data suggest that these patients might benefit most from surveillance colonoscopy.

Comparison of adenoma detection rate and proximal serrated polyp detection rate and their effect on post-colonoscopy colorectal cancer mortality in screening patients.

BACKGROUND: Patients with serrated polyps are at increased risk for post-colonoscopy colorectal cancer (PCCRC); however, evidence for a dedicated serrated polyp detection rate is lacking. The aim of this study was to investigate the association of the proximal serrated polyp detection rate (PSDR) and adenoma detection rate (ADR) with PCCRC death. METHODS: This was a retrospective analysis within the Austrian quality assurance program for screening colonoscopy. Spearman's rank coefficient was calculated for the assessment of association between ADR and PSDR. Whether ADR or PSDR were associated with colorectal cancer mortality was assessed by Cox proportional hazards model. RESULTS: 229/729 screening colonoscopies performed by 308 endoscopists were analyzed. The ADR (hazard ratio [HR] per 1 percentage point increase 0.98, 95 %CI 0.96-0.99) as well as the PSDR (HR per 1 percentage point increase 0.97, 95 %CI 0.94-0.99) were significantly associated with PCCRC death. The correlation coefficient of the ADR and PSDR calculated at every colonoscopy was 0.70 (95 %CI 0.70-0.71), and the corresponding PSDR value for an ADR performance standard of 25 % was 11.1 %. At the end of the study period, 86 endoscopists (27.9 %) reached an ADR of > 25 % and a PSDR of > 11.1 %. CONCLUSIONS: The ADR as well as the PSDR were associated with PCCRC death. Striving for a high PSDR in addition to a high ADR might reduce the risk for PCCRC mortality in patients undergoing screening colonoscopy.

Interval cancer after colonoscopy in the Austrian National Screening Programme: influence of physician and patient factors.

OBJECTIVE: Postscreening colorectal cancer (PSCRC) after screening colonoscopy is associated with endoscopists' performance and characteristics of resected lesions. Prior studies have shown that adenoma detection rate (ADR) is a decisive factor for PSCRC, but correlations with other parameters need further analysis and ADR may change over time. DESIGN: Cohort study including individuals undergoing screening colonoscopy between 1/2008 and 12/2019 performed by physicians participating in a quality assurance programme in Austria. Data were linked with hospitalisation data for the diagnosis of PSCRC (defined as CRC diagnosis >6 months after colonoscopy). ADR was defined dynamically in relation to the time point of subsequent colonoscopies; high-risk groups of patients were those with an adenoma ≥10 mm, or with high-grade dysplasia, or villous or tubulovillous histology, or a serrated lesion ≥10 mm or with dysplasia, or colonoscopies with ≥3 lesions. Main outcome was PSCRC for each risk group (negative colonoscopy, hyperplastic polyps, low-risk and high-risk group of patients) after colonoscopy by endoscopists with an ADR <20% compared with endoscopists with an ADR ≥20%. RESULTS: 352 685 individuals were included in the study (51.0% women, median age 60 years) of which 10.5% were classified as high-risk group. During a median follow-up of 55.4 months, 241 (0.06%) PSCRC were identified; of 387 participating physicians, 19.6% had at least one PSCRC (8.4% two or more). While higher endoscopist ADR decreased PSCRC incidence (HR per 1% increase 0.97, 95% CI 0.95 to 0.98), affiliation to the high-risk group of patients was also associated with higher PSCRC incidence (HR 3.27, 95% CI 2.36 to 4.00). Similar correlations were seen with regards to high-risk, and advanced adenomas. The risk for PSCRC was significantly higher after colonoscopy by an endoscopist with an ADR <20% as compared with an endoscopist with an ADR ≥20% in patients after negative colonoscopy (HR 2.01, 95% CI 1.35 to 3.0, p<0.001) and for the high-risk group of patients (HR 2.51, 95% CI 1.49 to 4.22, p<0.001). CONCLUSION: A dynamic calculation of the ADR takes into account changes over time but confirms the correlation of ADR and interval cancer. Both lesion characteristics and endoscopists ADR may play a similar role for the risk of PSCRC. This should be considered in deciding about appropriate surveillance intervals in the future.

Detection of high-risk polyps at screening colonoscopy indicates risk for liver and biliary cancer death.

BACKGROUND: Hepatobiliary cancers share risk factors with colorectal cancer (CRC), but there are no combined screening programs for these conditions. AIMS: The aim of this study was to assess whether patients with high-risk colonic polyps are more likely to die from liver related tumors than patients with a negative colonoscopy. METHODS: In this retrospective analysis of mortality data, Austrian screening participants were included. The absolute risk for hepatobiliary cancer death was calculated using the cumulative incidence method. We aimed to identify an association with time to death of hepatobiliary cancer by Cox proportional hazards model. RESULTS: 343,838 colonoscopies performed between 01/2007 and 12/2020 were included in the analysis, of which 17,678 (5.14%) revealed high-risk polyps. Overall hepatobiliary cancer mortality was more than twice as high in patients with high risk polyps (cumulative incidence 0.39%, 95% CI 0.37-0.41%) compared to patients with a negative colonoscopy (cumulative incidence 0.17%, 95% CI 0.17-0.17%). When adjusting for age and sex, having high-risk polyps at screening colonoscopy was significantly associated with hepatobiliary cancer death (HR 1.83, 95% CI 1.29- 2.59, p < 0.001). CONCLUSIONS: Patients with certain colonic polyp characteristics are at increased risk for mortality of liver malignancies. Further studies are needed to determine whether a structured additional screening for liver diseases and consecutive malignancies might be beneficial in these patients.

Colorectal Cancer and Precursor Lesion Prevalence in Adults Younger Than 50 Years Without Symptoms.

Importance: Incidence of colorectal cancer (CRC) is increasing among younger adults. However, data on precursor lesions in patients who are asymptomatic, especially those aged younger than 50 years, are lacking. Objective: To analyze the prevalence and number needed to screen (NNS) for adenomas, advanced adenomas, and serrated lesions, as well as the incidence of CRC in patients older than age 20 years. Design, Setting, and Participants: This cohort study was conducted among 296 170 patients who received a screening colonoscopy within a national screening colonoscopy registry from 2012 to 2018 in Austria, including 11 103 patients aged younger than 50 years. CRC incidence was analyzed using data from Statistic Austria from 1988 to 2018. Data were analyzed in September 2021. Main Outcome and Measures: The prevalence of adenomas and other lesions and the incidence of CRC in individuals aged 20 years or older were assessed. Results: Among 296 170 patients included in the study (median [IQR] age, 60 [54-68] years; 150 813 females [50.9%]), 11 103 patients (3.7%) were aged younger than 50 years and 285 067 patients (96.3%) were aged 50 years or older. Among patients younger than age 50 years, 1166 individuals (10.5%; NNS = 9) had adenomas and 389 individuals (3.9%; NNS = 26) had at least 1 advanced adenoma, while among those aged 50 years or older, 62 384 individuals (21.9%; NNS = 5) had adenomas and 19 680 individuals (6.9%; NNS = 15) had at least 1 advanced adenoma. Among 1128 males aged 40 to 44 years, 160 individuals (14.2%; NNS = 7) had at least 1 adenoma, and among 1398 females aged 40 to 44 years, 114 individuals (8.1%; NNS = 12) had at least 1 adenoma. The prevalence of adenomas for individuals aged 45 to 49 years vs 50 to 54 years was 490 of 2879 males (17.1%; NNS = 6) vs 8269 of 40 935 males (20.2%; NNS = 5) and 284 of 2792 females (10.2%; NNS = 10) vs 4997 of 40 303 females (12.4%; NNS = 8), respectively. Prevalence of adenomas changed from 61 of 498 individuals (12.4%) in 2008 to 150 of 1064 individuals (14.1%) in 2018 among those younger than 50 years and from 2646 of 12 166 individuals (21.8%) to 10 673 of 37 922 individuals (28.2%) among those aged 50 years and older. The prevalence of advanced adenomas changed from 20 individuals (4.0%) in 2008 to 55 individuals (5.2%) in 2018 in individuals younger than 50 years and from 888 individuals (7.3%) in 2008 to 2578 individuals (6.8%) in 2018 among those aged 50 years and older. Among individuals younger than age 50 years, CRC incidence per 100 000 individuals changed from 9.1 incidents in 1988 to 10.2 incidents in 2018 among males (average annual percentage change [AAPC], 0.5%; 95% CI, 0.1% to 1.0%) and from 9.7 incidents in 1988 to 7.7 incidents in 2018 among females, with a nonsignificant AAPC (-0.2%; 95% CI, -0.7% to 0.3%). Among individuals aged 50 years or older, CRC incidence per 100 000 individuals changed from 168 incidents in 1988 to 97 incidents in 2018 among females (AAPC, -1.8%; 95% CI, -1.9% to -1.6%), and 217 incidents in 1988 to 143 incidents in 2018 among males (AAPC, -1.2%; 95% CI, -1.3% to -1.1%). Conclusion: In this study, CRC incidence decreased after 1988 in Austria among individuals older than 50 years, while among patients younger than 50 years, incidence increased among males but decreased among females. Prevalence of adenomas increased in all age groups, while advanced adenoma prevalence increased among patients younger than 50 years but decreased in patients aged 50 years and older.

Solutions to problems of nonexistence of parameter estimates and sparse data bias in Poisson regression.

Poisson regression can be challenging with sparse data, in particular with certain data constellations where maximum likelihood estimates of regression coefficients do not exist. This paper provides a comprehensive evaluation of methods that give finite regression coefficients when maximum likelihood estimates do not exist, including Firth's general approach to bias reduction, exact conditional Poisson regression, and a Bayesian estimator using weakly informative priors that can be obtained via data augmentation. Furthermore, we include in our evaluation a new proposal for a modification of Firth's approach, improving its performance for predictions without compromising its attractive bias-correcting properties for regression coefficients. We illustrate the issue of the nonexistence of maximum likelihood estimates with a dataset arising from the recent outbreak of COVID-19 and an example from implant dentistry. All methods are evaluated in a comprehensive simulation study under a variety of realistic scenarios, evaluating their performance for prediction and estimation. To conclude, while exact conditional Poisson regression may be confined to small data sets only, both the modification of Firth's approach and the Bayesian estimator are universally applicable solutions with attractive properties for prediction and estimation. While the Bayesian method needs specification of prior variances for the regression coefficients, the modified Firth approach does not require any user input.

Impact of restrictions due to COVID-19 on a quality-assured screening colonoscopy program.

Background and study aims On February 25, 2020, the first patient was diagnosed with COVID-19 in Austria. On March 16, 2020, the Austrian government imposed restrictions and subsequently the Austrian Medical Association recommended minimizing screening examinations in compliance with government restrictions. The aims of this study were to evaluate the impact of this recommendation on the number of colonoscopies performed weekly and detection of non-advanced adenomas, advanced adenomas (AA) and colorectal cancer (CRC) and to calculate how many undetected adenomas could have developed into CRC. Methods We analyzed the number of colonoscopies and pathological findings within a quality assured national colorectal cancer screening program before the COVID-19 pandemic (March 1, t 2019 to September 1, 2019, Period 1) and compared those rates to months during which access to colonoscopy was limited (March 1, 2020 and September 1, 2020, Period 2) with a Wilcoxon-rank-test and a chi-square test. Results A total of 29,199 screening colonoscopies were performed during Period 1 and 24,010 during Period 2. The mean rate of colonoscopies per week during Period 1 was significantly higher than during Period 2 (808,35 [SD = 163,75] versus 594,50 [SD = 282,24], P  = 0.005). A total of 4,498 non-advanced adenomas were detected during Period 1 versus 3,562 during Period 2 ( P  < 0.001). In total 1,317 AAs and 140 CRCs were detected during Period 1 versus 919 AAs and 106 CRCs during Period 2. These rates did not differ significantly ( P  = 0.2 and P  = 0.9). Conclusions During the COVID-19 crisis, the number of colonoscopies performed per week was significantly lower compared to the year before, but there was no difference in the detection of CRCs and AAs.