Significant Reduction In Colorectal Cancer Mortality Research Articles

Positive impact of a faecal-based screening programme on colorectal cancer mortality risk.

The effectiveness of colorectal cancer (CRC) screening programs is directly related to participation and the number of interval CRCs. The objective was to analyse specific-mortality in a cohort of individuals invited to a CRC screening program according to type of CRC diagnosis (screen-detected cancers, interval cancers, and cancers among the non-uptake group). Retrospective cohort that included invitees aged 50-69 years of a CRC screening program (target population of 85,000 people) in Catalonia (Spain) from 2000-2015 with mortality follow-up until 2020. A screen-detected CRC was a cancer diagnosed after a positive faecal occult blood test (guaiac or immunochemical); an interval cancer was a cancer diagnosed after a negative test result and before the next invitation to the program (≤24 months); a non-uptake cancer was a cancer in subjects who declined screening. A total of 624 people were diagnosed with CRC (n = 265 screen-detected, n = 103 interval cancers, n = 256 non-uptake). In the multivariate analysis, we observed a 74% increase in mortality rate in the group with interval CRC compared to screen-detected CRC adjusted for age, sex, location and stage (HR: 1.74%, 95% CI:1.08-2.82, P = 0.02). These differences were found even when we restricted for advanced-cancers participants. In the stratified analysis for type of faecal occult blood test, a lower mortality rate was only observed among FIT screen-detected CRCs. CRC screening with the FIT was associated with a significant reduction in CRC mortality.

PO-052 Selenium status and survival from colorectal cancer in the european prospective investigation of cancer and nutrition

IntroductionSuboptimal levels of selenium (Se) or selenoprotein P (SELENOP), which is an antioxidant protein that also distributes Se from the liver to target tissues, may contribute to risk of colorectal cancer (CRC) development, as we previously showed using serum samples taken pre-diagnostically in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohortHughes et al, 2015 Int J Cancer 136: 1149–61). However, the relationship between Se and survival outcomes following cancer diagnosis is more uncertain. Here, we examined the association of Se status with mortality from CRC and overall mortality in the same study group.Material and methodsSe was measured by reflection X-ray fluorescence spectrometry and SELENOP by immunoluminometric sandwich assay. Multivariable adjusted Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of the association between Se and SELENOP and CRC-death and all-cause mortality.Results and discussionsHigher levels of Se showed non-significant inverse associations with reduction in both CRC and overall mortality: Respective multivariable adjusted HRs for the fifth quintile versus the first quintile (HRQ5 vs. Q1) were 0.76 (95% CI: 0.52–1.11, Ptrend=0.10), and 0.82 (95% CI: 0.56–1.16, Ptrend=0.14). Higher levels of SELENOP were also not associated with a statistically significant reduction in CRC mortality (HRQ5 vs. Q1 = 0.83, 95% CI: 0.57–1.19, Ptrend=0.33). However, higher SELENOP concentrations were associated with a significant reduction in overall mortality (HRQ5 vs. Q1 = 0.70, 95% CI: 0.50–0.98, Ptrend=0.05). Similar results were also obtained by tumour site and sex. Possible interactions of potential effect modifiers and sensitivity analyses showed no considerable change in these estimates, although CRC stage data sensitivity analyses were significant for the association between Se and overall mortality (HRQ5 vs. Q1 = 0.89, 95% CI: 0.80–0.99, Ptrend=0.03).ConclusionWe found no major association of Se status markers with survival after CRC diagnosis, but an association of SELENOP with overall mortality. Detailed investigation of Se metabolism is needed to further explore relevance for CRC prognosis especially for individuals of suboptimal SELENOP status.

Selenium status and survival from colorectal cancer in the European prospective investigation of cancer and nutrition

Introduction Suboptimal levels of selenium (Se) or selenoprotein P (SELENOP), which is an antioxidant protein that also distributes Se from the liver to target tissues, may contribute to risk of colorectal cancer (CRC) development, as we previously showed using serum samples taken pre-diagnostically in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort [1] . However, the relationship between Se and survival outcomes following cancer diagnosis is more uncertain. Here, we examined the association of Se status with mortality from CRC and overall mortality in the same study group. Methods Se was measured by total reflection X-ray fluorescence and SELENOP by immunoluminometric sandwich assay. Multivariable-adjusted Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of the association between Se and SELENOP and CRC death and all-cause mortality. Results Higher levels of Se showed non-significant inverse associations with reduction in both CRC and overall mortality: respective multivariable-adjusted HRs for the fifth quintile versus the first quintile (HRQ5 vs. Q1) were 0.76 (95% CI: 0.52–1.11, Ptrend = 0.10), and 0.82 (95% CI: 0.56–1.16, Ptrend = 0.14). Higher levels of SELENOP were also not associated with a statistically significant reduction in CRC mortality (HRQ5 vs. Q1 = 0.83, 95% CI: 0.57–1.19, Ptrend = 0.33). However, higher SELENOP concentrations were associated with a significant reduction in overall mortality (HRQ5 vs. Q1 = 0.70, 95% CI: 0.50–0.98, Ptrend = 0.05). Similar results were also obtained by tumour site and sex. Possible interactions of potential effect modifiers and sensitivity analyses showed no considerable change in these estimates, although CRC stage data sensitivity analyses were significant for the association between Se and overall mortality (HRQ5 vs. Q1 = 0.89, 95% CI: 0.80–0.99, Ptrend = 0.03). Conclusions We found no major association of Se status markers with survival after CRC diagnosis, but an association of SELENOP with overall mortality. Detailed investigation of Se metabolism is needed to further explore relevance for CRC prognosis especially for individuals of suboptimal SELENOP status.

Colonoscopy and Colorectal Cancer Mortality in the Veterans Affairs Health Care System: A Case-Control Study.

Colonoscopy is widely used in the Veterans Affairs (VA) health care system for colorectal cancer (CRC) prevention, but its effect on CRC mortality is unknown. To determine whether colonoscopy is associated with decreased CRC mortality in veterans and whether its effect differs by anatomical location of CRC. Case-control study. VA-Medicare administrative data. Case patients were veterans aged 52 years or older who were diagnosed with CRC between 2002 and 2008 and died of the disease by the end of 2010. Case patients were matched to 4 control patients without prior CRC on the basis of age, sex, and facility. Conditional logistic regression was performed to calculate odds ratios (ORs) for exposure to colonoscopy, with adjustment for race, Charlson Comorbidity Index score, selected chronic conditions, nonsteroidal anti-inflammatory drug use, and family history of CRC. Exposure to colonoscopy was determined from 1997 to 6 months before CRC diagnosis in case patients and to a corresponding date in control patients. Subgroup analysis was performed for patients who had undergone screening colonoscopy. A total of 4964 case patients and 19856 control patients were identified. Case patients were significantly less likely to have undergone any colonoscopy (OR, 0.39 [95% CI, 0.35 to 0.43]). Colonoscopy was associated with reduced mortality for left-sided cancer (OR, 0.28 [CI, 0.24 to 0.32]) and right-sided cancer (OR, 0.54 [CI, 0.47 to 0.63]). The results were similar for patients who had undergone screening colonoscopy (overall OR, 0.30 [CI, 0.24 to 0.38]). Sensitivity analyses that varied the interval between CRC diagnosis and colonoscopy exposure did not affect the primary findings. Unmeasured confounding. In this study using national VA-Medicare data, colonoscopy was associated with significant reductions in CRC mortality among veterans and was associated with greater benefit for left-sided cancer than right-sided cancer. U.S. Department of Veterans Affairs.

Comparing mortality of colorectal cancer and gastrointestinal bleeding among patients with long-term use of low dose aspirin: A population-based study of 689,209 patients.

527 Background: Aspirin, commonly used for prevention of cardiovascular and cerebrovascular diseases, is well-known to protect against colorectal cancer (CRC) development but increase risk of gastrointestinal bleeding (GIB). Few large-scale studies have compared the benefit and risk of long-term aspirin usage. This cohort study aims to evaluate the use of low-dose aspirin to prevent CRC and the risk of GIB associated with the aspirin use. Methods: A population-based clinical dataset was used to compare incidence and mortality of CRC and GIB patients receiving low-dose aspirin with sex-and-age matched controls (in 1:2 ratio). Patients with aspirin≤6 months were excluded. Clinical data of 206,243 aspirin users (mean dose 80 mg/day, mean duration 7.7 years) and 482,966 non-users were included. All patients must have at least 10-year follow up on clinical outcome. Results: Among aspirin users 5,776 (2.80%) were diagnosed with CRC; 2,097 (1.02%) died of the malignancy. 16,483 (3.41%) non-users were diagnosed with CRC; 7,963 (1.65%) died of CRC. Using the cox-proportional hazard regression, aspirin usage showed a modest but significant reduction in CRC mortality (HR = 0.65; 95% CI = 0.62 to 0.69). On the other hand, 11,187 (5.42%) aspirin users developed GIB, and 841 (0.41%) died. 15,186 (3.14%) non-users developed GIB, and 1,682 patients (0.35%) died. Aspirin users showed modest but significant increased risk of GIB-related mortality (HR = 1.24; 95% CI = 1.14 to 1.35). Conclusions: The long-term use of low dose aspirin shows preventive effect on CRC, but also increases the associated GIB risk. Considerations of prophylactic use of aspirin should balance the benefit and the risk of this treatment to the target population. [Table: see text]

Associations between county-level surgeon density and colorectal cancer (CRC) mortality.

6018 Background: Strong associations between surgical procedure volumes and patient outcomes have been consistently observed for many types of cancers. Whether surgeon density in a population has a similar impact on cancer outcomes is unclear. Our aims were to 1) explore the effect of US county-level surgeon density on CRC mortality and on annual changes in death, 2) compare the relative importance of colorectal surgeon (CS) versus general surgeon (GS) density on these CRC outcomes and 3) identify other county characteristics associated with decreased mortality. Methods: Using county-level data from the Area Resource File, US Census and National Cancer Institute, we developed multivariate regression models to determine the effect of a) CS and b) GS on overall CRC mortality as well as on changes in death between 2002 and 2006, while controlling for CRC incidence, county demographics and other socioeconomic factors. Results: A total of 1,767 US counties were included: mean CRC incidence and death rates were 64.9 and 19.9 per 100,000 people; 45% were metropolitan and 55% were rural counties; mean CS and GS densities were 1.3 and 4.1 per 100,000 people, respectively. When compared to counties with no CS and no GS, those with at least of one of these surgeons had a statistically significant decrease in CRC-specific mortality (beta coefficients -0.35 and -0.2 for CS and GS, respectively; p=0.014). Increasing the county-level density of surgeons improved outcomes, but increasing it beyond 6 CS or 14 GS per 100,000 people did not continue to result in significant reductions in CRC mortality. Similar associations between surgeon density and annual changes in CRC-related death were observed. Counties with a high proportion of Medicare enrollees also showed increased CRC mortality. Conclusions: The presence of CS and GS at the county level is each associated with lower mortality from CRC. However, there appears to be a ceiling effect at which point further increases in their density do not produce continued improvements in CRC outcomes. A balanced strategy of allocating healthcare resources and distributing the surgical workforce evenly across all counties will likely offer the most substantial population-based improvements in CRC mortality.

Radiation oncologist density and colorectal cancer mortality.

605 Background: Although the use of radiation therapy is increasing, there exists geographic variation among the distribution of radiation oncologists. The impact of this variation on colorectal cancer (CRC) outcomes remains unexplored. The goal of this study was to determine the effect of radiation oncologist density on CRC mortality. Methods: Using county-level data from the 2008 Area Resource File, National Program for Cancer Registries, and US Centers for Disease Control, a regression model was constructed for CRC mortality, controlling for county-level categorized radiation oncologists density, demographics, socioeconomic status and existing healthcare facilities. Results: There was a statistically significant reduction in CRC mortality (reduction in mortality ranging from 12% to 47%, p<0.001) associated with counties that possessed at least one radiation oncologist. However, increasing the county density to greater than two radiation oncologists per 100,000 people had no statistically significant reduction in CRC mortality. Conclusions: The presence of a radiation oncologist is associated with lowered mortality for CRC within that county, but increasing radiation oncologist density does not yield further improvements. Therefore, as the use of radiation therapy to treat CRC increases, a detailed understanding of distribution of the radiation oncologists is essential for providing the greatest improvement in cancer mortality outcomes. [Table: see text] No significant financial relationships to disclose.

Associations between county-level surgeon density and colorectal cancer (CRC) mortality.

511 Background: Strong associations between surgeon procedure volumes and patient outcomes have been observed for many types of cancers. Whether surgeon density in a population has a similar impact on cancer outcomes is unclear. Our aims were to 1) explore the effect of US county-level surgeon density on CRC mortality and on annual changes in death, 2) compare the relative importance of colorectal surgeon (CS) versus general surgeon (GS) density on these CRC outcomes, and 3) identify other county characteristics associated with reduced mortality. Methods: Using county-level data from the Area Resource File, US Census and National Cancer Institute, we developed multivariate regression models to determine the effect of a) CS and b) GS on overall CRC mortality and changes in death between 2002 and 2006, while controlling for CRC incidence, county demographics and other socioeconomic factors. Results: A total of 1,187 US counties were included: mean CRC incidence and death rates were 64.9 and 19.9, respectively; 57% were metropolitan and 43% were rural counties; mean CS and GS densities were 1.23 and 1.94 per 100,000 people, respectively. When compared to counties with no CS and no GS, those with at least of one of these surgeons had a statistically significant decrease in CRC-specific mortality (beta coefficients were -0.035 and -0.051 for CS and GS, respectively; p=0.014). Increasing the county-level density of surgeons improved outcomes, but increasing it beyond 8 CS or 12 GS per 100,000 people did not continue to result in significant reductions in CRC mortality. Similar associations between surgeon density and annual changes in CRC-related death were observed. Counties with a high proportion of Medicare enrollees also showed increased CRC mortality. Conclusions: The presence of CS and GS at the county level is each associated with lower mortality from CRC. However, there appears to be a ceiling effect at which point further increases in their density do not produce continued improvements in CRC outcomes. A balanced strategy of allocating healthcare resources and distributing the surgical workforce evenly across all counties will likely offer the most substantial population-based improvements in CRC mortality. No significant financial relationships to disclose.

Colorectal Cancer Mortality after Colonoscopy: A Population-based Study: 2010 ACG Colorectal Cancer Prevention Abstract Award

Purpose: There are limited data on mortality from colorectal cancer (CRC), after a colonoscopy. The objective of our study was to determine if there is a reduction in CRC mortality after colonoscopy in Manitoba, compared to the CRC mortality among the general population in Manitoba. Methods: We identified all individuals with a colonoscopy as their first lower gastrointestinal endoscopy between April 1, 1987 and September 30, 2007 from Manitoba's provincial physicians' billing claims database and followed them to March 31, 2008, death or out-migration from the province. Individuals less than 50 or greater than 80 years old at the index colonoscopy or with prior resective colorectal surgery or CRC or IBD were excluded. CRC mortality, after the index colonoscopy was compared to that in the general population by standardized mortality ratios (SMRs). Stratified analyses were performed to determine CRC mortality for different age groups at index colonoscopy, sex, duration of follow-up and site of CRC. Results: 54,803 individuals (24,342 men; 30,461 women) were followed-up for 310,718 person-years. There was a 29% reduction in overall CRC mortality [SMR 0.71;95% confidence interval (CI): 0.61-0.82], a 47% reduction in mortality from distal CRC (SMR 0.53;95% CI: 0.42-0.67) and no reduction in mortality from proximal CRC (SMR 0.94;95%CI: 0.77-1.17). The reduction in mortality from distal CRC remained significant for follow-up beyond 10 years. Conclusion: Colonoscopy in usual clinical practice can lead to a significant reduction in CRC mortality, but the benefit is not uniform for CRC occurring at different sites in the colon.

Progress and Challenges in Colorectal Cancer Screening and Surveillance

Colorectal cancer is a leading cause of cancer death throughout the world. There is evidence that screening of average-risk individuals can result in mortality reduction with early cancer detection and cancer prevention by detection and removal of cancer precursor lesions. The optimal form of screening is not clear. Fecal screening tests can be performed at home at low initial cost, but current versions lack high sensitivity for cancer precursor lesions, and tests need to be repeated at regular intervals. Adherence to repeat testing for negative tests and referral for colonoscopy for positive tests are important elements of program effectiveness. Structural examinations of the colon are more invasive and may result in detection of both early cancer and cancer precursor lesions. Every screening program has advantages and limitations, but each program ultimately depends on quality and patient adherence.

COX-2 inhibition and colorectal cancer

Mortality in patients with advanced colorectal cancer (CRC) remains high. Epidemiologic studies show that individuals taking nonselective, nonsteroidal anti-inflammatory drugs, including aspirin, have a significant reduction in CRC mortality, compared with those not taking these agents. The recent characterization of cyclooxygenase-1 and -2 (COX-1 and COX-2) isoforms has led to an expanded understanding of how nonsteroidal anti-inflammatory drugs may help prevent polyp formation. Cyclooxygenase enzymes are required for the conversion of arachidonic acid to prostaglandins. COX-2 mediates the inflammatory effects of COX activity, is induced by a wide spectrum of growth factors and proinflammatory cytokines, and is overexpressed in numerous premalignant and malignant lesions, including CRC. Treatment with the selective COX-2 inhibitor celecoxib has shown promising results in the prevention of CRC. Numerous studies show that this COX-2 selective inhibitor is a potent suppressor of colon polyps both in animal models for familial adenomatous polyposis and in patients with this condition. This has led to the US Food and Drug Administration approval of celecoxib for the treatment of patients with familial adenomatous polyposis. The role of celecoxib in cancer treatment is still evolving. Recent studies have identified a potential benefit for adding celecoxib to standard CRC chemotherapy regimens to increase their efficacy and reduce their associated toxicity.