Gemma Binefa

Colorectal cancer: From prevention to personalized medicine

Colorectal cancer (CRC) is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors. CRC develops through a gradual accumulation of genetic and epigenetic changes, leading to the transformation of normal colonic mucosa into invasive cancer. CRC is one of the most prevalent and incident cancers worldwide, as well as one of the most deadly. Approximately 1235108 people are diagnosed annually with CRC, and 609051 die from CRC annually. The World Health Organization estimates an increase of 77% in the number of newly diagnosed cases of CRC and an increase of 80% in deaths from CRC by 2030. The incidence of CRC can benefit from different strategies depending on its stage: health promotion through health education campaigns (when the disease is not yet present), the implementation of screening programs (for detection of the disease in its early stages), and the development of nearly personalized treatments according to both patient characteristics (age, sex) and the cancer itself (gene expression). Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application, not all strategies meet the criteria required for screening tests in population programs; the three most accepted tests are the fecal occult blood test (FOBT), colonoscopy and sigmoidoscopy. FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe. Due to its non-invasive nature and low cost, it is one of the most accepted techniques by population. CRC is a very heterogeneous disease, and with a few exceptions (APC, p53, KRAS), most of the genes involved in CRC are observed in a small percentage of cases. The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy. In recent years, the use of DNA, RNA and protein markers in different biological samples has been explored as strategies for CRC diagnosis. Although there is not yet sufficient evidence to recommend the analysis of biomarkers such as DNA, RNA or proteins in the blood or stool, it is likely that given the quick progression of technology tools in molecular biology, increasingly sensitive and less expensive, these tools will gradually be employed in clinical practice and will likely be developed in mass.

Colorectal cancer mortality in Spain: trends and projections for 1985-2019.

Background and aim To describe colorectal cancer (CRC) mortality trends during 1985–2004 and to estimate CRC mortality projections for the period 2005–2019 in Spain. Material and methods A Bayesian age-period-cohort analysis has been carried out to investigate the effect of the age, period, and birth cohort on CRC mortality in Spain. Mortality projections until 2019 were based on the age-period-cohort model. Results During 1985–1994, CRC mortality increased in both sexes (3.9% yearly in men and 1.5% in women). After 1995, CRC mortality increased in men (1.6%) and leveled off in women (−0.6%). Colon cancer mortality increased for the whole period in men, this increase being lower in the second decade (1985–1994: 5.0%; 1995–2004: 1.8%). In women, colon cancer mortality increased in the first decade (2.8%) and leveled off during the second decade (−0.1%). Rectal cancer mortality increased in men (1.2%) and decreased in women (−1.1%) during the whole study period. Projections showed an increase in the number of CRC deaths in men older than 60 years and a level off in women. Conclusion Although mass screening for CRC in Spain has not been available, the favorable recent changes in CRC mortality trends observed after 1995 could be related to progress in diagnosis and treatment. The projected number of deaths could be used as reference scenario for assessing future impact of new treatments as well as the potential impact of future population-based screening when introduced.

False-positive results from colorectal cancer screening in Catalonia (Spain), 2000-2010.

Objective To identify factors associated with a false-positive result in a population-based colorectal cancer (CRC) screening programme with the faecal occult blood test (FOBT) in Catalonia between 2000 and 2010. Methods The study population consisted of participants of the Catalan CRC screening programme with a positive FOBT who underwent a colonoscopy for diagnostic confirmation from 2000 to 2010. A false-positive result was defined as having a positive test but detecting no high-risk adenoma or cancer in the follow-up colonoscopy. Multivariate logistic regression models were performed to identify sociodemographic and screening variables related to false-positive results. Adjusted odds ratios (OR) and their 95% confidence intervals (CI) were estimated. Results Over the screening period, 1074 (1.7%) of the 63,332 screening tests had a positive result in the Catalan CRC screening programme. The false-positive proportion was 55.2% (n = 546). Women were more likely to have a positive FOBT in the absence of CRC neoplasia than men (adjusted OR = 2.91; 95% CI: 2.22–3.28). During the first prevalence round, the proportion of false-positive results was higher than in subsequent rounds (69.5% vs. 48.9%; P < 0.05). Re-screening and having a bleeding pathology such as haemorrhoids or anal fissures were also associated with a false-positive result. Conclusion The proportion of false-positive results and the associated risks should be estimated to provide an eligible population with more reliable information on the adverse effects of screening.

Colorectal cancer screening: strategies to select populations with moderate risk for disease

OBJECTIVE to analyse the association between rectal bleeding or a family history of colorectal cancer (CRC) and the results obtained in two rounds of a CRC screening pilot programme performed in L Hospitalet, Barcelona, Spain. SUBJECTS males and females (50-69 years) were the target population. Together with the invitation letter, they received a questionnaire in which they were asked about rectal bleeding, family history of CRC and related neoplasms. The screening test was a guaiac-based faecal occult blood test (FOBT), and colonoscopy for positive tests. RESULTS 25,829 FOBT were performed in 18,405 individuals. Information on rectal bleeding and a family history of CRC were obtained for 9,849 and 9,865 cases, respectively. Male sex (OR = 1.32), 60-69 years of age (OR = 1.48), rectal bleeding (OR = 1.84) and history of CRC (OR = 1.54) were independent predictors of positive FOBT. With regard to colonoscopy, a greater risk of diagnosing advanced neoplasm was observed among men (OR = 2.47) and subjects with a family history of CRC (OR = 1.98). CONCLUSIONS CRC screening programmes must have instruments that make it possible to select the candidate population and the possibility of offering a study suited to the risk of individuals who are not susceptible to population screening by means of FOBT.

Defining the Role of the Nurse in Population-Based Cancer Screening Programs

Nurses are pivotal in cancer prevention and early detection, but the nurses role in cancer screening programs has been described only in very general terms without specification of activities needed to develop the role. To identify the set of activities that compose the role of the cancer screening nurse, the authors of the current article performed a critical descriptive literature review to document nursing involvement in cancer screening, covering articles published from 2000-2012. A total of 726 potentially relevant studies were identified, and 22 of those were included in the review. Nurses carry out follow-up, coordinate treatment, ensure continuity throughout the process, provide up-to-date and pertinent information to facilitate patient knowledge and choice, work to ensure coordination among the various levels of care, provide ongoing training, lead research and publications concerning daily practice, and collaborate in investigation oriented toward early detection. The literature revealed that the nurses role in cancer screening involves case management as the main activity as well as, exceptionally, carrying out diagnostic tests.

Hallazgos colonoscópicos del estudio piloto de cribado de cáncer colorrectal realizado en Cataluña.

Objective: to evaluate lesions detected in two screening rounds performed in a pilot screening programme for colorectal cancer in Catalonia, Spain. Material and methods: a colorectal cancer screening pro gramme was initiated in 2000. The target population included men and women aged 50-69 years. Screening consisted of biennial gua iac-based fecal occult blood testing (FOBT), and colonoscopy for participants with a positive FOBT. Any polyps found were re moved, and biopsies were performed for any masses. Results: colonoscopies were performed in 442 of 495 people with positive FOBT. In 213 (48.2%), 36 invasive cancers, 121 high-risk adenomas, 29 low-risk adenomas, and 27 hyperplastic polyps were diagnosed. Lesion size was smaller than 10 mm in 25.8% of cases. Most detected lesions (37.2%) were located in the distal colon, followed by the proximal colon (5.7%) and both loca tions (5.2%). Advanced neoplasm was significantly associated with male gender and distal location. The prevalence of advanced proximal neoplasms among patients with no distal polyps was 5.1%. Conclusions: the most common lesions detected by colonoscopy were high-risk adenomas located in the distal colon. FOBT is a suitable method for detecting small precancer lesions during population screening, and is thus a key factor in reducing the incidence of colorectal cancer.

Colorectal Cancer Screening Programme in Spain: Results of Key Performance Indicators After Five Rounds (2000–2012)

Effective quality assurance is essential in any screening programme. This article provides a unique insight into key quality indicators of five rounds of the first population-based colorectal cancer screening programme implemented in Spain (2000–2012), providing the results according to the type of screening (prevalent or first screen and incident or subsequent screen) and test (guaiac or immunochemical). The total crude participation rate increased from 17.2% (11,011) in the first round to 35.9% (22,988) in the last one. Rescreening rate was very high (88.6% in the fifth round). Positivity rate was superior with the faecal immunochemical test (6.2%) than with the guaiac-based test (0.7%) (p < 0.0001) and detection rates were also better with the immunochemical test. The most significant rise in detection rate was observed for high risk adenoma in men (45.5 per 1,000 screened). Most cancers were diagnosed at an early stage (61.4%) and there was a statistically significant difference between those detected in first or subsequent screening (52.6% and 70.0% respectively; p = 0.024). The availability of these results substantially improves data comparisons and the exchange of experience between screening programmes.

Prescription drugs associated with false-positive results when using faecal immunochemical tests for colorectal cancer screening

BACKGROUND The most common side effect in population screening programmes is a false-positive result which leads to unnecessary risks and costs. AIMS To identify factors associated with false-positive results in a colorectal cancer screening programme with the faecal immunochemical test (FIT). METHODS Cross-sectional study of 472 participants with a positive FIT who underwent colonoscopy for confirmation of diagnosis between 2013 and 2014. A false-positive result was defined as having a positive FIT (≥20μg haemoglobin per gram of faeces) and follow-up colonoscopy without intermediate/high-risk lesions or cancer. RESULTS Women showed a two-fold increased likelihood of a false-positive result compared with men (adjusted OR, 2.3; 95%CI, 1.5-3.4), but no female-specific factor was identified. The other variables associated with a false-positive result were successive screening (adjusted OR, 1.5; 95%CI, 1.0-2.2), anal disorders (adjusted OR, 3.1; 95%CI, 2.1-4.5) and the use of proton pump inhibitors (adjusted OR, 1.8; 95%CI, 1.1-2.9). Successive screening and proton pump inhibitor use were associated with FP in men. None of the other drugs were related to a false-positive FIT. CONCLUSION Concurrent use of proton pump inhibitors at the time of FIT might increase the likelihood of a false-positive result. Further investigation is needed to determine whether discontinuing them could decrease the false-positive rate.

Repeated screening for colorectal cancer with fecal occult blood test in Catalonia, Spain.

The objective of this study was to explore the variables associated with repeated screening for colorectal cancer (CRC) among individuals aged 50–69 years in Catalonia, Spain. We selected for the study all individuals (n=11 969) screened by a population-based CRC screening program in 2004 and who were eligible for rescreening in two years. A multilevel logistic regression model was derived. The contextual variables were the percentage of people with less than primary studies and the percentage of CRC screening participation. The individual variables used were: sex, age, CRC screening (prior to 2004), guaiac fecal occult blood test result, ease of recruitment, and number of tests used. The rescreening rate was 87%. No differences according to sex and age were found. The strongest barrier for CRC rescreening was an inconclusive fecal occult blood test result at baseline screening [odds ratio (OR): 0.24; 95% confidence intervals (CI): 0.20–0.29]. Individuals who agreed to participate just after receiving the screening invitation were more likely to accept a second screen compared with those who received a reminder letter six weeks later (OR: 1.53; 95% CI: 1.36–1.73). Those individuals who lived in a neighborhood with a higher educational level were more willing to rescreen (OR: 1.22; 95% CI: 1.03–1.45) than those who lived in more deprived areas. Rescreening was highly adequate in our program, reflecting satisfaction with the service received at screening. Strategies to enhance initial screening participation for CRC and to improve quality throughout the screening process should be prioritized.

Fecal hemoglobin concentration as a measure of risk to tailor colorectal cancer screening: are we there yet?

The aim of this paper was to examine the distribution of fecal hemoglobin (f-Hb) concentration in a Spanish colorectal cancer screening population according to sociodemographic characteristics and analyze whether f-Hb was associated with clinical outcomes (type of lesion and its location). From September 2009 to November 2012, we sent 77 744 invitations to individuals aged 50–69 years to provide one sample of feces. f-Hb was measured on samples from 27 606 screenees (35.5%). Colonoscopy findings and pathology data were collected on the 1406 screenees with f-Hb greater than 100 ng Hb/ml (20 mg Hb/g feces). The Mann–Whitney U-test and the Kruskal–Wallis test were used to compare f-Hb (median) according to sociodemographic variables, clinical outcomes, and histological features of adenomas. f-Hb from greater than 100 ng Hb/ml was categorized into quartiles. Regression models were used to determine whether f-Hb was a risk predictor of colorectal lesions. f-Hb was associated directly with the severity of the colorectal lesions. An overlap between individuals with a negative colonoscopy and those with a low-risk adenoma was observed. High-grade dysplasia, villous histology, distal location, and increasing size were all features associated with an increased f-Hb level. f-Hb could be used in individual risk assessment to determine surveillance strategies for colorectal cancer screening.