Detection of colorectal cancer and advanced neoplasia during first surveillance interval after detection of adenomas in fecal immunochemical test cancer screening: a nationwide study.

BACKGROUND: Adenoma surveillance guidelines are based on non-fecal immunochemical test (FIT)-based screening settings. However, colorectal cancer (CRC) risk may be different in FIT-positive screening populations. We evaluated the CRC and advanced adenoma risk within the recommended surveillance periods in the Danish FIT-based CRC screening program for participants with intermediate or high risk adenomas according to 2010 European guidelines. Furthermore, we estimated CRC risk for those who were not recommended surveillance according to European Society of Gastrointestinal Endoscopy (ESGE) 2020 guidelines. METHODS: Using nationwide health registries, we identified 17 936 FIT-screening participants from 2014-2017 with adenomas undergoing surveillance (high risk 1 year, intermediate risk 3 years). Participants with a follow-up examination were included (N = 10 068). Relative risk (RR) of CRC and advance adenoma was compared between intermediate and high risk groups and between intermediates who were recommended surveillance (S) or no surveillance (NS) according to 2020 ESGE guidelines. RESULTS: During surveillance, CRC occurred in 0.59% of the high risk group and 1.11% of the intermediate risk group (RR 0.53 [95%CI 0.34-0.84]). The high risk group had a 24% increased risk of advanced adenoma. CRC occurred in 1.69% of the intermediateNS group and 0.87% of the intermediateS group (RR 1.94 [95%CI 1.18-3.21]), and RR for advanced adenoma was 1.19 (95%CI 1.03-1.37). CONCLUSION: CRC detection was lower among participants rated at higher risk at initial CRC screening. Findings at first screen-derived colonoscopy might not be as good a predictor of CRC risk in a FIT-positive screening population.

Less Invasive Primary Treatment for Colorectal Cancer After Implementation of National Screening: A Nationwide Cohort Study.

BACKGROUND: The effect of organized colorectal cancer (CRC) screening on type of primary treatment remains sparsely investigated. This study evaluated the difference in primary treatment strategy between patients diagnosed with screen-detected (SD-CRC) and non-screen-detected colorectal cancer (NSD-CRC) in a national CRC screening program. METHODS: This was a retrospective national register-based cohort study. Data on patients aged between 50 and 75 years and diagnosed with SD-CRC or NSD-CRC were retrieved from the national colorectal cancer screening database and the Danish Colorectal Cancer Group database. Outcomes related to surgical invasiveness were compared between the two cohorts. Differences were expressed as relative risks using log-binomial generalized linear regression models. UICC stage IV specific outcomes were analyzed using the same method. All analyses were adjusted for sex, age, type of cancer (colonic/rectal), and Charlson comorbidity index. RESULTS: The study included 4707 patients with SD-CRC and 7328 with NSD-CRC. Therapeutic flexible endoscopy (SD-CRC: n = 636 vs. NSD-CRC: n = 334, RR: 2.50, P < 0.001), (robotic-assisted) laparoscopic resection ((n = 616 vs. n = 773, RR: 1.27, P < 0.001), n = 2759 vs. n = 3471, RR: 1.11, P < 0.001), and radical resection (n = 3890 vs. n = 4834, RR: 1.02, P = 0.002) were significantly more frequent in the SD-CRC group. The rates of emergency priority (n = 32 vs. n = 562, RR: 0.09, P < 0.001), open surgery (n = 391 vs. n = 1410, RR: 0.53, P < 0.001), supplementary organ resection (n = 259 vs. n = 860, RR: 0.56, P < 0.001), and stoma formation (n = 526 vs. n = 1040, RR: 0.89, P = 0.007) were significantly lower in the SD-CRC group. The rate of patients undergoing surgery with UICC stage IV disease was significantly higher in the SD-CRC group (SD-CRC: n = 262, NSD-CRC: n = 994, RR: 1.43, P < 0.001). CONCLUSION: SD-CRC remained associated with less invasive primary surgical treatment following adjustment for potential healthy user bias. UICC stage IV disease may be less advanced in patients with SD-CRC.

Effect of colorectal cancer screening on colorectal cancer surgery outcomes: nationwide cohort study.

BACKGROUND: National colorectal cancer screening commenced in Denmark in 2014. Little is known about the effects of organized colorectal cancer screening on intraoperative and postoperative events. The aim of this nationwide cohort study was to evaluate the difference in intraoperative and postoperative outcomes between patients with screen-detected colorectal cancer and non-screen-detected colorectal cancer within the first 90 days after surgery. METHODS: National register data were collected for Danish residents diagnosed with colorectal cancer between January 2014 and March 2018. Outcomes for the two cohorts were reported as relative risk or weighted mean difference. Intraoperative outcomes were blood loss, blood transfusion, tumour perforation, and organ lesion. Postoperative outcomes were complications (surgical and non-surgical) and 90-day mortality. Discrete data estimates were calculated from a general linear model. Analyses were adjusted for potential healthy user bias with respect to sex, age, location of the cancer (colon/rectum), and Charlson co-morbidity index. RESULTS: In total, 10 606 patients were included. Compared with patients in the non-screen-detected colorectal cancer group (4497 patients), patients in the screen-detected colorectal cancer group (6109 patients) had reduced intraoperative blood loss (-52 mL, 95% c.i. -67 to -37, P < 0.001), a shorter duration of hospitalization (-2.3 days, 95% c.i. -2.8 to -1.8, P < 0.001), and reduced rates of intraoperative organ lesion (0.76, 95% c.i. 0.59 to 0.99, P = 0.042), surgical complications (0.79, 95% c.i. 0.73 to 0.87, P < 0.001), non-surgical complications (0.68, 95% c.i. 0.60 to 0.78, P < 0.001), and 90-day mortality (0.29, 95% c.i. 0.21 to 0.39, P < 0.001). CONCLUSION: In comparison with non-screen-detected colorectal cancer, surgery for screen-detected colorectal cancer remains associated with improvement in several intraoperative and early postoperative outcomes after considering healthy user bias.

Breast cancer mortality in Norway after the introduction of mammography screening.

An organized mammography screening program was gradually implemented in Norway during the period 1996-2004. Norwegian authorities have initiated an evaluation of the program. Our study focused on breast cancer mortality. Using Poisson regression, we compared the change in breast cancer mortality from before to during screening in four counties starting the program early controlling for change in breast cancer mortality during the same time in counties starting the program late. A follow-up model included death in all breast cancers diagnosed during the follow-up period. An evaluation model included only breast cancers diagnosed in ages where screening was offered. The study group had been invited for screening one to three times and followed for on average of 5.9 years. In the follow-up model, 314 breast cancer deaths were observed in the study group, and 523, 404 and 638, respectively, in the four control groups. The ratio between the changes in breast cancer mortality between early and late starting counties was 0.93 (95% confidence interval [CI] 0.77-1.12). In the evaluation model, this ratio was 0.89 (95% CI: 0.71-1.12). In Norway, where 40% of women used regular mammography prior to the program, the implementation of the organized mammography screening program was associated with a statistically nonsignificant decrease in breast cancer mortality of around 11%.

Nationwide mammography screening participation in Denmark during the COVID-19 pandemic: An observational study.

Background: In most of the world, the mammography screening programmes were paused at the start of the pandemic, whilst mammography screening continued in Denmark. We examined the mammography screening participation during the COVID-19 pandemic in Denmark. Methods: The study population comprised all women aged 50-69 years old invited to participate in mammography screening from 2016 to 2021 in Denmark based on data from the Danish Quality Database for Mammography Screening in combination with population-based registries. Using a generalised linear model, we estimated prevalence ratios (PRs) and 95% confidence intervals (CIs) of mammography screening participation within 90, 180, and 365 d since invitation during the pandemic in comparison with the previous years adjusting for age, year and month of invitation. Results: The study comprised 1,828,791 invitations among 847,766 women. Before the pandemic, 80.2% of invitations resulted in participation in mammography screening within 90 d, 82.7% within 180 d, and 83.1% within 365 d. At the start of the pandemic, the participation in screening within 90 d was reduced to 69.9% for those invited in pre-lockdown and to 76.5% for those invited in first lockdown. Extending the length of follow-up time to 365 d only a minor overall reduction was observed (PR = 0.94; 95% CI: 0.93-0.95 in pre-lockdown and PR = 0.97; 95% CI: 0.96-0.97 in first lockdown). A lower participation was, however, seen among immigrants and among women with a low income. Conclusions: The short-term participation in mammography screening was reduced at the start of the pandemic, whilst only a minor reduction in the overall participation was observed with longer follow-up time, indicating that women postponed screening. Some groups of women, nonetheless, had a lower participation, indicating that the social inequity in screening participation was exacerbated during the pandemic. Funding: The study was funded by the Danish Cancer Society Scientific Committee (grant number R321-A17417) and the Danish regions.

Adherence to follow-up after the exit cervical cancer screening test at age 60-64: A nationwide register-based study.

BACKGROUND: In Denmark, human papillomavirus (HPV) testing has replaced cytology in primary cervical cancer screening for women aged 60-64; at this age, women are invited for the last (exit) screening test within the national organized program. AIM: We investigated the adherence of these women to the recommended follow-up after a non-negative (positive or inadequate) HPV test and the overall resource use during that follow-up. MATERIALS & METHODS: We included all 2926 women aged 60-64 years with nonnegative HPV screening tests between March 2012 and December 2016. All relevant follow-up tests and procedures were retrieved until the end of 2020 from the highly complete Danish administrative health registers, and the data were linked at the individual level. We determined the extent to which the adherence patterns followed the national recommendations for follow-up and estimated the total numbers of tests and diagnostic procedures utilized during the entire process. RESULTS: In total, only 26% of women had follow-up in accordance with the recommendations; 4% had no follow-up, 46% had insufficient follow-up, and 24% had more follow-up than recommended. We estimated that 17% of women remained in follow-up for longer than 4 years. The average numbers of diagnostic tests and procedures used after positive HPV screening were higher than expected, even among women who had insufficient follow-up, that is, those who received less invasive procedures than recommended, or experienced delays in receiving those procedures. CONCLUSION: To conclude, we found that the patterns of follow-up of women with nonnegative primary HPV screening tests at 60-64 often diverged from the recommendations. Addressing these inconsistencies in follow-up by providing evidence for optimal clinical management should help improve the quality of screening programs and secure an equal and reliable follow-up care service for all women.

Mammography activity in Norway 1983 to 2008.

BACKGROUND: In Norway, an organized screening mammography program, the Norwegian Breast Cancer Screening Program (NBCSP) started in four counties in 1996 and became nationwide in 2004. We collected data on pre-program screening activity, and in view of this activity we evaluated the potential impact of the program on breast cancer mortality in Norway. METHODS: We searched data sources on mammography activity in Norway. Three data sources reported on examination activity, and two on self-reported examinations. We aimed at calculating annual number of women examined by mammography from 1983 to 2008, and coverage rate in program and non-program Norwegian counties. RESULTS: The annual number of women examined increased from 5000 in 1983 to 110,000 in 1993 to reach its maximum of 131,000 in 2002, excluding program examinations. The annual number of women examined in the organized program increased from 1996 to a steady state about 190,000 in 2004. Prior to start of the organized program, 40% of women in target age groups reported to have had mammography examination. During the years 1996-2002, 64% of first participants in the organized program reported to have been examined previously. Assuming that the Norwegian program would in absence of prior screening have decreased breast cancer mortality by 25%, and that the activity in- and outside the organized program were equally effective, the measured effect of the organized program would under actual circumstances be a reduction of 11%. CONCLUSION: The example of Norway illustrates that although monitoring of screening outcome is highly warranted, this may be seriously jeopardized if use of mammography examinations was widespread prior to implementation of an organized program.

Colonoscopy-related complications in a nationwide immunochemical fecal occult blood test-based colorectal cancer screening program.

BACKGROUND: The Danish national screening program for colorectal cancer (CRC) consists of an immunochemical fecal occult blood test (iFOBT) followed by colonoscopy. The Danish Colorectal Cancer Screening Database (DCCSD) records data on the incidence of hospital-registered complications after colonoscopy. However, the validity of these data is unknown, and the incidence of complications is potentially underreported. OBJECTIVE: To evaluate the validity of the colonoscopy complications registered in the DCCSD by using medical records as the reference. Further, to evaluate the incidence of complications leading to hospital contact. METHODS: Among 14,671 individuals with a positive iFOBT result and a colonoscopy procedure performed from March 3, 2014 to December 31, 2014, we selected 295 individuals for medical record review. We calculated sensitivity as the proportion of true complications registered in the DCCSD out of all complications found in the medical records, and the positive predictive value (PPV) as the number of true complications in the DCCSD out of all DCCSD-registered complications. On the basis of the medical record data, we calculated the incidence proportion of hospital-registered complications overall and by subtype. RESULTS: In total, we reviewed 286 records and found 102 individuals with at least one complication. The sensitivity of the DCCSD for any complication was 29.4% (95% CI: 20.8-39.3) and the PPV was 88.2% (95% CI: 72.6-96.7). On the basis of the medical record data, the incidence proportion of any complication after colonoscopy was 0.70% (95% CI: 0.57-0.84) and that of perforation or lesion was 0.10% (95% CI: 0.06-0.17); bleeding, 0.41% (95% CI: 0.31-0.53); post-polypectomy syndrome, 0.16% (95% CI: 0.10-0.24); and other medical complications, 0.04 (95% CI: 0.02-0.09). CONCLUSION: The DCCSD has low sensitivity for complications, and improvements in data registration are warranted. The incidence proportion of any hospital-treated post-colonoscopy complication was 0.70% in 2014, which was the first year of the Danish national CRC screening program. This is within the range of complications reported by other studies.

Danish Quality Database for Mammography Screening.

AIM: The Danish Quality Database for Mammography Screening (DKMS) was established in 2007, with the aim to monitor, sustain, and improve the quality of the Danish national breast cancer screening program. STUDY POPULATION: All Danish women aged 50-69 years who were invited every 2 years for breast cancer screening in the nationwide program since July 10, 2007. MAIN VARIABLES: The DKMS consists of data retrieved from the five regional invitation systems, the National Pathology Registry, and the National Registry of Patients. The DKMS covers the entire screening process and includes variables required to determine the following eleven indicators: 1) radiation exposure, 2) participation among invited women and participation within the target population, 3) time between screening and result, 4) screening interval, 5) recall for further diagnostics, 6) interval cancers consisting of women diagnosed with breast cancer between screening rounds, 7) invasive breast tumors, 8) node-negative cancers, 9) invasive tumors ≤10 mm, 10) ratio of surgery for benign vs malignant lesions, and 11) breast-conserving therapy. DESCRIPTIVE DATA: As of August 10, 2015, the database included data from 888,151 unique women who have been invited to one or more screenings. In the first three screening rounds, 641,835 (round I), 580,452 (round II), and 641,938 (round III) women were invited, and participation increased from 79% to 84%. In the third round, 79% of the screened women received their result within ten working days, 2.7% of the screened women were recalled for further diagnostics, 82% of the women operated for invasive carcinomas were node negative, and 40% of the women had the tumor size of ≤10 mm. CONCLUSION: The DKMS has successfully evaluated the quality of the nationwide Danish breast cancer screening program against international quality standards. The quality of the Danish program complies well with international standards particularly as regards to the clinical aspects.

Body weight and sensitivity of screening mammography.

AIM: Obese women tend to participate less in breast cancer screening than normal weight women. However, obese women have fattier breast than normal weight women, and screening mammography works better in fatty than in dense breasts. One might, therefore, hypothesise that obese women would actually benefit more from screening than other women. METHODS: We combined data from the Danish Diet, Cancer and Health study and the organised population-based screening mammography programme in Copenhagen, Denmark. Women were categorised according to body mass index (BMI) (<20; 20 to <25; 25 to <30; 30 to <35, and 35+). We measured recall rate, sensitivity and specificity for subsequent screens with a 2-year follow-up period. RESULTS: The study included 6787 women. The recall rate varied from 1.4% for women with BMI <20 to 1.9% for women with BMI 35+, test for trend p = 0.86. Sensitivity varied from 42% (95% confidence interval [CI] 20-64%) for women with BMI <20 to 100% (95% CI 69-100%) for women with BMI 35+, test for trend p = 0.015. Specificity was fairly constant across BMI levels, being on average 98.8%, test for trend p = 0.79. CONCLUSION: This study showed that obese women were the ones with the highest sensitivity of screening mammography, while the specificity of screening remained stable across weight groups. Screening programmes should be organized to encourage these women to overcome obstacles for participation.

Restriction of human papillomavirus DNA testing in primary cervical screening to women above age 30: systematic review.

Cervical screening with human papillomavirus (HPV) testing is less specific for high-grade cervical intraepithelial neoplasia (≥CIN3) than cytology. The aim of this systematic review was to determine whether a restriction of HPV testing to women aged at least 30 years would eliminate the problem. On the basis of the data from randomized controlled trials, we calculated the relative detection of CIN1 and CIN2, and the relative risks of false-positive tests (positive tests without subsequent ≥CIN3) per age group and trial for HPV testing versus cytology. For women aged at least 30 years in trials with a low cytology abnormality rate, detection of CIN1 increased significantly by 50-90% in the two trials with reported data; detection of CIN2 was doubled in three trials; the risks of false-positive HPV tests were also doubled. In trials with a high cytology abnormality rate, these risks were similar for HPV testing and cytology. Adverse effects of HPV testing were for both types of cytology settings, generally higher for women below than above the age of 30. Adverse effects were less common among women aged at least 30 years than among younger women. However, in older women HPV testing still led to more CIN1/CIN2 diagnoses and false-positive tests than cytology.

Type of hormone therapy and risk of misclassification at mammography screening.

OBJECTIVE: Current users of hormone therapy (HT) are known to have a lower accuracy of mammography screening than do never users. We studied whether the risk of misclassification depends on type of hormone, administration, regimen, and dose of the therapy. METHODS: We linked data from mammography screening registers with drug prescription registers from Fyn, Denmark to identify current and never HT users among screening participants. We compared false-positive risks and interval cancer proportions between current users of different HT preparations, taking women's age, breast density, screen number, and age of comparison mammogram into account. RESULTS: Estrogen therapy users had a significantly higher false-positive risk when the administration was by injection instead of oral (relative risk [RR], 2.37; 95% CI, 1.37-4.09). Women using sequential estrogen plus progestogen therapy had a significantly higher false-positive risk (RR, 1.94; 95% CI, 1.16-3.26) and a nonsignificantly higher interval cancer proportion (RR, 4.29; 95% CI, 0.69-26.53) when the administration of both hormones was transdermal instead of oral. Using tibolone instead of comparable hormones gave a nonsignificantly lower false-positive risk and a nonsignificantly higher interval cancer proportion. CONCLUSIONS: Our data showed increased risks of misclassification at mammography screening among women using estrogen injections or transdermal, sequential estrogen plus progestogen. Tibolone seems to offer no advantage regarding accuracy of screening mammography.

Estimating the benefits of mammography screening: the impact of study design.

BACKGROUND: Mammography screening is justifiable only if it leads to reduction in breast cancer mortality. However, evaluation of routine screening is not straightforward, as no unscreened control group is available. We report here on a cohort study of the effect of routine mammography on breast cancer mortality, and illustrate how variations in the analytic approach can affect the conclusions. METHODS: We used data from the mammography screening program in Copenhagen, Denmark, for the period 1991-2001. We used local historical, concurrent regional, and historical regional control groups, and included only deaths from breast cancers diagnosed during the observation periods. We examined the impact of various control groups, of including all breast cancer deaths, and of using individual data versus routine statistics. RESULTS: Combining all 3 control groups gave an estimated 25% reduction in breast cancer mortality. The estimate was 20% using only a local historical control group, and 9% using only a concurrent regional control group. Including all breast cancer deaths resulted in an estimate of 21% reduction in breast cancer mortality. Using routine statistics and a concurrent regional control group resulted in an estimated increase of 6% in breast cancer mortality. CONCLUSION: Estimated changes in breast cancer mortality following the introduction of routine mammography ranged from a 25% reduction (based on the best methodology) to a 6% increase with a less rigid study design. The estimated effect of routine mammography on breast cancer mortality is thus highly dependent on study design.

Breast cancer mortality in Copenhagen after introduction of mammography screening: cohort study.

OBJECTIVES: To evaluate the effect on breast cancer mortality during the first 10 years of the mammography service screening programme that was introduced in Copenhagen in 1991. DESIGN: Cohort study. SETTING: The mammography service screening programme in Copenhagen, Denmark. PARTICIPANTS: All women ever invited to mammography screening in the first 10 years of the programme. Historical, national, and historical national control groups were used. MAIN OUTCOME MEASURES: The main outcome measure was breast cancer mortality. We compared breast cancer mortality in the study group with rates in the control groups, adjusting for age, time period, and region. RESULTS: Breast cancer mortality in the screening period was reduced by 25% (relative risk 0.75, 95% confidence interval 0.63 to 0.89) compared with what we would expect in the absence of screening. For women actually participating in screening, breast cancer mortality was reduced by 37%. CONCLUSIONS: In the Copenhagen programme, breast cancer mortality was reduced without severe negative side effects for the participants.