Routine Fecal Occult Blood Screening and Colorectal Cancer Mortality in Sweden.

Importance: Population-based colorectal cancer (CRC) screening programs are implemented worldwide, but there are difficulties evaluating their effectiveness. The magnitude of routine CRC screening effectiveness regarding cancer-specific mortality is unclear. Objective: To evaluate cancer-specific mortality associated with early vs late or no invitation for routine CRC screening using fecal occult blood testing. Design, Setting, and Participants: This prospective cohort study was performed in the region of Stockholm-Gotland, Sweden, between January 1, 2008, and December 31, 2021. All individuals of the target population of screening born from 1938 to 1954 were included. Data were analyzed from December 12, 2022, to June 25, 2023. Exposures: Individuals were invited early (2008-2012), late (2013-2015), or not at all to screening with biennial guaiac-based fecal occult blood test. The early invitation group was considered the exposure group and the late or no invitation group was considered the control group. Main Outcomes and Measures: The main outcome was cancer-specific mortality, defined as CRC registered in the Cancer Register with CRC as underlying cause of death in the Cause of Death Register. Excess mortality was calculated as all-cause deaths among the individuals with CRC subtracted from the expected number of deaths had they not had CRC. Poisson regression analysis based on deaths and person-years was used to estimated mortality rate ratio (RR) with 95% CIs, adjusted for follow-up years and attained age. Results: In total, 379 448 individuals (193 436 [51.0%] female) were invited for CRC screening, including 203 670 individuals in the exposure group and 175 778 in the control group. The mean screening participation rate was 63.3%, and there was a maximum of 14 years follow-up. There were 834 CRC deaths in 2 190 589 person-years in the exposure group, compared with 889 CRC deaths in 2 249 939 person-years in the control group. Individuals who underwent early CRC screening had reduced adjusted risk of CRC mortality (RR, 0.86; 95% CI, 0.78-0.95) and excess mortality (RR, 0.84; 95% CI, 0.75-0.93). Conclusions and Relevance: This prospective cohort study of routine screening with fecal occult blood testing found a 14% decrease in CRC mortality associated with screening. The true association of screening with reduced mortality is expected to be higher due to some coexistence of testing in the control group and CRC deaths diagnosed more than 2 years after screening.

Colorectal cancer screening with faecal immunochemical test: Patterns of participation.

OBJECTIVE: To evaluate participation and participation patterns in a population-based screening programme for colorectal cancer (CRC) using the faecal immunochemical test (FIT). METHODS: All individuals invited to three consecutive screening rounds in the population-based CRC screening between October 2015 and December 2020 in the Stockholm-Gotland Region, Sweden were included. Patterns of participation were assessed. RESULTS: The study included 26 541 individuals which resulted in 79 623 screening events. The overall uptake rate was 71.5% and women had a significantly higher participation rate. The participation rate increased significantly between the first and third screening round for both men and women, and the increase was larger among men than women (66.1 to 70.7% vs. 73.1 to 75.4%). In total, 80.9% participated at least once. Consistent participation was the most common participation pattern (61.0%). The probability of attending all three consecutive rounds after initial participation was 87.7%. Over the three rounds, 17.4% participated after a reminder letter. Screening individuals attending after a reminder letter had a higher proportion of drop-outs in the following screening round compared to initial participants (15.4% vs 6.2%). CONCLUSION: A constant and high participation rate was observed in population-based FIT-screening for CRC. Initial participation was a strong predictor for continuous participation. The need for a reminder letter before participation was a risk factor for subsequent drop-out.

Autoimmune and Metabolic Diseases and the Risk of Early-Onset Colorectal Cancer, a Nationwide Nested Case-Control Study.

Incidence of early-onset (<50 years) colorectal cancer (EOCRC) is increasing in developed countries. The aim was to investigate autoimmune and metabolic conditions as risk factors for EOCRC. In a nationwide nested case-control study, we included all EOCRC cases in Sweden diagnosed during 2007-2016, together with controls, matched for birth year, sex, and county. Information on exposure of autoimmune or metabolic disease was collected from the National Patient Register and Prescribed Drugs Registry. Hazard ratios (HR) as measures of the association between EOCRC and the exposures were estimated using conditional logistic regression. In total, 2626 EOCRC patients and 15,756 controls were included. A history of metabolic disease nearly doubled the incidence hazard of EOCRC (HR 1.82, 95% CI 1.66-1.99). A sixfold increased incidence hazard of EOCRC (HR 5.98, 95% CI 4.78-7.48) was seen in those with inflammatory bowel disease (IBD), but the risk increment decreased in presence of concomitant metabolic disease (HR 3.65, 95% CI 2.57-5.19). Non-IBD autoimmune disease was not statistically significantly associated with EOCRC. IBD and metabolic disease are risk factors for EOCRC and should be considered in screening guidelines.

Interval cancers in a population-based screening program for colorectal cancer with gender-specific cut-off levels for fecal immunochemical test.

OBJECTIVE: To evaluate interval cancers (IC) in the population-based Swedish regional colorectal cancer (CRC) screening program of Stockholm-Gotland, which uses gender-specific cut-off levels for the fecal immunochemical test (FIT). METHODS: All individuals aged 60-69 in Stockholm-Gotland invited to the screening program in October 2015 to September 2017 were followed up 2 years after invitation. Cut-off level for a positive FIT was 40 µg/g in women and 80 µg/g in men. Those with a positive FIT were referred to colonoscopy. Screening-detected CRC (SD-CRC) and IC after negative FIT (FIT-IC) or negative screening colonoscopy (Colonoscopy-IC) were identified in the Swedish colorectal cancer register. The IC rate was calculated as IC/(FIT negatives + negative screening colonoscopies). The IC incidence rate (ICs among negatives per 100,000 person-years) in different sex and age groups was compared to the mean CRC incidence before regional screening implementation. Test sensitivity was defined as SD-CRC/(SD-CRC + FIT-IC). RESULTS: Approximately 214,400 individuals were invited, and in 3521 screening colonoscopies 257(6.3%) SD-CRCs were detected. During follow-up, 124 FIT-IC and 7 Colonoscopy-IC were diagnosed, yielding an IC rate of 12.6 and 6.0 per 10,000 negatives (p = 0.00005) and a test sensitivity of 62% and 75% (p = 0.01) in men and women respectively. The IC incidence rate compared to CRC incidence was non-significantly lower in women. CONCLUSION: In the population-based screening program of Stockholm-Gotland with a cut-off of 40 µg/g in women and 80 µg/g in men, the test sensitivity was higher and the IC rate was lower in women, which might imply lowering the cut-off level in men. However, the IC incidence rate relative to the CRC incidence was similar in both genders.

Gender-specific cut-off levels in colorectal cancer screening with fecal immunochemical test: A population-based study of colonoscopy findings and costs.

OBJECTIVE: In the population-based Swedish regional colorectal cancer (CRC) screening program of Stockholm-Gotland using the fecal immunochemical test (FIT), gender-specific cut-off levels of fecal hemoglobin are applied, since previous studies have indicated a lower sensitivity of FIT for CRC in women. The aim was to evaluate the diagnostic yield and the screening costs overall and per detected CRC of this strategy. METHODS: All individuals aged 60-69 invited to screening in 2015-2017 were included. Cut-off level for positive FIT was 40 µg/g in women and 80 µg/g in men. Those with a positive FIT were referred to colonoscopy. The yield of CRC and screening cost for the study period were assessed and compared to cut-off levels of 80 µg/g in both genders. RESULTS: Approximately 230,000 individuals were invited. Overall participation rates were 72% in women and 65% in men (p < 0.05). FIT was positive in 4256 individuals (2.7% in both genders). In 3758 colonoscopies, 258 (6.9%) CRCs were detected. The positive predictive value for CRC was significantly higher in men (8.3% vs. 5.8%). In 120 women with CRC, 28 (23%) had FIT < 80 µg/g. Negative colonoscopies were more common in women (24% vs. 17%, p < 0.05). Total costs for the study period were 52,000,000SEK (≈5,200,000€), i.e. 16% higher compared to using cut-off levels of 80 µg/g in both genders, and corresponding to a 3% increment in cost per detected CRC. CONCLUSION: The high rate of CRC detected in women in the lowest FIT category outweighs the minor reduction in screening costs if the same cut-off level was used as for men.

Long-Term Results after Anastomotic Leakage following Rectal Cancer Surgery: A Comparison of Treatment with Endo-Sponge and Transanal Irrigation.

OBJECTIVE: We aimed to evaluate long-term results in patients from regular health care treated with endoscopic transanal closure system, that is, endoscopic vacuum-assisted closure system (EVAC) compared to transanal irrigation. METHODS: In this retrospective, medical chart-based, observational study, we included patients with anastomotic leakage after low anterior resection for rectal cancer from 3 Stockholm hospitals 2006-2016 and compared time to first stoma closure in a Kaplan-Meier model and the proportion of patients who were stoma-free at end of follow-up. RESULTS: Anastomotic leakage was found in 81 patients who were followed up in median 5.9 years (min-max: 0.53-13). EVAC was used on 14 (17%) patients and transanal irrigation on 34 (42%) patients. The remaining 33 (41%) patients either got a permanent colostomy or were treated only with antibiotics and percutaneous drainage. Treatment with EVAC or transanal irrigation led to similar rates of stoma closure, both when comparing all patients, and when comparing patients with similar defects. At the end of follow-up, 43% of patients treated with EVAC and 50% of patients treated with repeated irrigation were stoma-free (p = 0.75). CONCLUSIONS: We found no evidence of better outcomes in patients treated with EVAC. The study was, however, limited by small sample size.

Gender-specific cut-offs in colorectal cancer screening with FIT: Increased compliance and equal positivity rate.

OBJECTIVE: Using quantitative Faecal Immunochemical Test (FIT) in colorectal cancer screening enables adjustment of the cut-off for a positive test. As men have higher stool blood levels and higher prevalence of colorectal neoplasia, different cut-off levels can be chosen for men and women. We evaluated participation and positivity rates switching from guaiac-based faecal occult blood test (gFOBT) (Hemoccult®) to FIT (OC-Sensor), using gender-specific cut-offs. METHODS: The colorectal cancer screening programme of Stockholm-Gotland, Sweden, started in 2008 and invited individuals aged 60-69 to biennial testing using gFOBT. From 1 October 2015 the test was switched to FIT, with positivity cut-offs of 40 (200) and 80 (400) µg Hb/g (ng/mL) faeces for women and men, respectively. The first year was evaluated for compliance and positivity, number of reminders and incorrect/inadequate tests, compared with gFOBT in the preceding 12-month period. RESULTS: There were 127,030 and 87,269 individuals invited to screening with gFOBT and FIT, respectively. The change of test increased overall participation by 11.9% (95% confidence interval 11.5%-12.3%) from 56.5% to 68.4% ( p < 0.001). The increase was larger in men (14.3%) than women (9.7%), and in those aged 60-64 (14.2%) than those aged 65-69 (8.7%). The positivity rate was 2.6% in women and 2.5% in men. There was a lower rate of reminders and incorrect/inadequate tests with FIT. CONCLUSIONS: Within a well-organised colorectal cancer screening programme, changing the test from gFOBT to FIT markedly increased participation, especially among men, and in the younger age group. With a lower cut-off in women than men, the positivity rate was similar.

Initial participation as a predictor for continuous participation in population-based colorectal cancer screening.

OBJECTIVES: To assess patterns and probabilities of participation in multiple rounds of colorectal cancer screening. METHODS: All individuals who were invited to participate in population-based colorectal cancer screening in the Stockholm-Gotland region in Sweden between 1 January 2008 and 30 September 2015 were included in the study. Guaiac-based faecal occult blood testing was used. All individuals invited to the three first consecutive screening rounds were included in the analysis. RESULTS: There were 346,168 individuals eligible for invitation to screening. The average participation rate during the follow-up period was 60%. Eligible individuals could be invited 1-4 times, depending on age at first invitation. Of 48,959 individuals invited to the three first consecutive rounds of screening, 71% participated at least once, and 50% participated in all three rounds. Participation at first invitation was a predictor for participation in subsequent rounds, and the likelihood of continuous participation following participation in the first round was 84%. Of those who attended the first and second rounds, 93% also participated in the third round. Similar patterns of consistency were seen among non-participants. For individuals not participating in the first screening round, the likelihood of consistent non-participation was 71. CONCLUSIONS: Participation in the first round of screening is a strong predictor for participation in subsequent rounds. Therefore, reducing barriers for initial participation is a key for achieving consistent participation over several rounds in organized colorectal cancer screening programmes.

Complications after colonoscopy and surgery in a population-based colorectal cancer screening programme.

OBJECTIVES: To report complications after colonoscopy and surgery in patients with neoplasia detected through a population based colorectal cancer (CRC) screening programme in the capital region of Sweden. METHODS: Patients who after a positive FOBT screening result underwent colonoscopy from 1 January 2008 to 30 June 2012 were included. Mortality and complications within 30 days after colonoscopy or subsequent surgery were identified through national registers, and complications were assessed through review of medical charts. Complications were graded using the Clavien-Dindo classification. RESULTS: After 2984 colonoscopies, the complication rate was 1%. The risk of post-polypectomy bleeding was 14/1000. The risk of perforation was 1/1000 after a diagnostic colonoscopy and 2.5/1000 after a colonoscopy with polypectomy. One patient developed a post-polypectomy syndrome. There was one death which was not related to the colonoscopy. After surgery for 37 adenomas and 155 CRCs, the total complication rates were 27% and 50%, respectively. The rate of anastomotic leakage was 13% and 12% after surgery for adenomas and CRC, respectively. There were no deaths after surgery. The overall complication rate after colonoscopy and surgery for adenomas and cancer was 4%. CONCLUSIONS: Overall complication rates were acceptable and mortality low; however, the rate of anastomotic leakage after surgery for both adenomas and CRC was higher than expected.

Predicting lymph node metastases in early rectal cancer.

AIM: In this population-based study, the aim was to investigate risk factors for lymph node metastases and to construct a risk stratification index with relevance for pre-operative planning in T1 and T2 rectal cancers. METHODS: Data were retrieved from The Swedish Rectal Cancer Register, a mandatory, national, prospectively collected data base. All T1 and T2 rectal cancers treated with abdominal resection surgery without neo-adjuvant or adjuvant radio-chemotherapy from 2007 to 2010 were analysed. T-stage, sm-level, histologic differentiation, mucinous tumour type, blood vessel- and perineural infiltration, tumour location (in cm from the anal verge), age and gender were evaluated as potential predictors of lymph node metastases, using uni- and multivariate logistic regression. RESULTS: T2-stage (odds ratio [OR]=2.0), poor differentiation (OR=6.5) and vascular infiltration (OR=4.3) were identified as significant risk-factors for lymph node metastases in the multivariate analysis. The risk stratification index shows the risk for lymph node metastases gradually increasing from 6% to 65% and 11% to 78% in T1 and T2 cancers respectively, when adding the risk factors one by one. CONCLUSION: There is a considerable span in the risk for lymph node metastases between low risk T1 and high risk T2 rectal cancer. Using the risk stratification-model, with the concept of local excision as a macro-biopsy with standby for subsequent immediate radical resection surgery in high-risk cases, could benefit patients by providing the advantages of local excision yet ensuring adequate oncologic outcome.