Dolores Salas

Colonoscopy versus Fecal Immunochemical Testing in Colorectal-Cancer Screening

BACKGROUND Colonoscopy and fecal immunochemical testing (FIT) are accepted strategies for colorectal-cancer screening in the average-risk population. METHODS In this randomized, controlled trial involving asymptomatic adults 50 to 69 years of age, we compared one-time colonoscopy in 26,703 subjects with FIT every 2 years in 26,599 subjects. The primary outcome was the rate of death from colorectal cancer at 10 years. This interim report describes rates of participation, diagnostic findings, and occurrence of major complications at completion of the baseline screening. Study outcomes were analyzed in both intention-to-screen and as-screened populations. RESULTS The rate of participation was higher in the FIT group than in the colonoscopy group (34.2% vs. 24.6%, P<0.001). Colorectal cancer was found in 30 subjects (0.1%) in the colonoscopy group and 33 subjects (0.1%) in the FIT group (odds ratio, 0.99; 95% confidence interval [CI], 0.61 to 1.64; P=0.99). Advanced adenomas were detected in 514 subjects (1.9%) in the colonoscopy group and 231 subjects (0.9%) in the FIT group (odds ratio, 2.30; 95% CI, 1.97 to 2.69; P<0.001), and nonadvanced adenomas were detected in 1109 subjects (4.2%) in the colonoscopy group and 119 subjects (0.4%) in the FIT group (odds ratio, 9.80; 95% CI, 8.10 to 11.85; P<0.001). CONCLUSIONS Subjects in the FIT group were more likely to participate in screening than were those in the colonoscopy group. On the baseline screening examination, the numbers of subjects in whom colorectal cancer was detected were similar in the two study groups, but more adenomas were identified in the colonoscopy group. (Funded by Instituto de Salud Carlos III and others; ClinicalTrials.gov number, NCT00906997.).

Cancer screening in Spain

OBJECTIVE To describe the current status of breast, colorectal and cervical cancer screening in Spain. METHODOLOGY The situation was analysed on the basis of data drawn from surveys conducted in each autonomous region (Comunidad Autónoma). RESULTS Currently, breast cancer screening coverage is 100%. In 2007, overall participation was 67.0% with an adherence of 91.2%. The detection rate was 3.4 per thousand, 15.1% intraductal and 30% invasive <1 cm in diameter, with 65% showing axilary node negative. Colorectal cancer screening had been implemented in six regions (4.5% of the target population). Participation ranged from 17.2% to 42.3%, with positive test percentages ranging from 1.7 per thousand (guaiac) to 9.5% (immunological). The invasive cancer detection rate was 1.7 per thousand (guaiac) and 3.4 per thousand (immunological). In most cases, cervical cancer screening was undertaken opportunistically, with an estimated coverage of 69.0%. CONCLUSIONS In Spain, cancer screening is being conducted in accordance with national and international recommendations. The fact that screening programmes are operated as a network has led to a high degree of consensus as to the methodology and information systems to be used to enable joint evaluation.

Modifiable endoscopic factors that influence the adenoma detection rate in colorectal cancer screening colonoscopies

BACKGROUND Adenoma detection rate (ADR) has become the most important quality indicator for colonoscopy. OBJECTIVE The aim of this study was to investigate which modifiable factors, directly related to the endoscopic procedure, influenced the ADR in screening colonoscopies. DESIGN Observational, nested study. SETTING Multicenter, randomized, controlled trials. PATIENTS Asymptomatic people aged 50 to 69 years were eligible for a multicenter, randomized, controlled trial designed to compare colonoscopy and fecal immunochemical testing in colorectal cancer screening. A total of 4539 individuals undergoing a direct screening colonoscopy were included in this study. INTERVENTION Colonoscopy. MAIN OUTCOME MEASUREMENTS Bowel cleansing, sedation, withdrawal time in normal colonoscopies, and cecal intubation were analyzed as possible predictors of adenoma detection by using logistic regression analysis, adjusted for age and sex. RESULTS In multivariate analysis, after adjustment for age and sex, factors independently related to the ADR were a mean withdrawal time longer than 8 minutes (odds ratio [OR] 1.51; 95% CI, 1.17-1.96) in normal colonoscopies and split preparation (OR 1.26; 95% CI, 1.01-1.57). For advanced adenomas, only withdrawal time maintained statistical significance in the multivariate analysis. For proximal adenomas, withdrawal time and cecal intubation maintained independent statistical significance, whereas only withdrawal time longer than 8 minutes and a <10-hour period between the end of preparation and colonoscopy showed independent associations for distal adenomas. LIMITATIONS Only endoscopic variables have been analyzed. CONCLUSION Withdrawal time was the only modifiable factor related to the ADR in colorectal cancer screening colonoscopies associated with an increased detection rate of overall, advanced, proximal, and distal adenomas.

Effect of protocol-related variables and women's characteristics on the cumulative false-positive risk in breast cancer screening

BACKGROUND Reducing the false-positive risk in breast cancer screening is important. We examined how the screening-protocol and womens characteristics affect the cumulative false-positive risk. METHODS This is a retrospective cohort study of 1565364 women aged 45-69 years who underwent 4739498 screening mammograms from 1990 to 2006. Multilevel discrete hazard models were used to estimate the cumulative false-positive risk over 10 sequential mammograms under different risk scenarios. RESULTS The factors affecting the false-positive risk for any procedure and for invasive procedures were double mammogram reading [odds ratio (OR)=2.06 and 4.44, respectively], two mammographic views (OR=0.77 and 1.56, respectively), digital mammography (OR=0.83 for invasive procedures), premenopausal status (OR=1.31 and 1.22, respectively), use of hormone replacement therapy (OR=1.03 and 0.84, respectively), previous invasive procedures (OR=1.52 and 2.00, respectively), and a familial history of breast cancer (OR=1.18 and 1.21, respectively). The cumulative false-positive risk for women who started screening at age 50-51 was 20.39% [95% confidence interval (CI) 20.02-20.76], ranging from 51.43% to 7.47% in the highest and lowest risk profiles, respectively. The cumulative risk for invasive procedures was 1.76% (95% CI 1.66-1.87), ranging from 12.02% to 1.58%. CONCLUSIONS The cumulative false-positive risk varied widely depending on the factors studied. These findings are relevant to provide women with accurate information and to improve the effectiveness of screening programs.Background: Reducing the false-positive risk in breast cancer screening is important. We examined how the screening-protocol and womens characteristics affect the cumulative false-positive risk. Methods: This is a retrospective cohort study of 1 565 364 women aged 45–69 years who underwent 4 739 498 screening mammograms from 1990 to 2006. Multilevel discrete hazard models were used to estimate the cumulative false-positive risk over 10 sequential mammograms under different risk scenarios. Results: The factors affecting the false-positive risk for any procedure and for invasive procedures were double mammogram reading [odds ratio (OR) = 2.06 and 4.44, respectively], two mammographic views (OR = 0.77 and 1.56, respectively), digital mammography (OR = 0.83 for invasive procedures), premenopausal status (OR = 1.31 and 1.22, respectively), use of hormone replacement therapy (OR = 1.03 and 0.84, respectively), previous invasive procedures (OR = 1.52 and 2.00, respectively), and a familial history of breast cancer (OR = 1.18 and 1.21, respectively). The cumulative false-positive risk for women who started screening at age 50–51 was 20.39% [95% confidence interval (CI) 20.02–20.76], ranging from 51.43% to 7.47% in the highest and lowest risk profiles, respectively. The cumulative risk for invasive procedures was 1.76% (95% CI 1.66–1.87), ranging from 12.02% to 1.58%. Conclusions: The cumulative false-positive risk varied widely depending on the factors studied. These findings are relevant to provide women with accurate information and to improve the effectiveness of screening programs.

Tumor phenotype and breast density in distinct categories of interval cancer: results of population-based mammography screening in Spain

IntroductionInterval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories.MethodsWe included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd’s scale and was conflated into: <25%; 25 to 50%; 50 to 75%; >75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2-. The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided.ResultsForty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (<25%) than in denser breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; <0.001). False-negatives and occult tumors had similar phenotypic characteristics to screening-detected cancers, extreme breast density being strongly associated with occult tumors (OR = 6.23 (95% CI:2.65-14.66)). Minimal-sign cancers were biologically close to true interval cancers but showed no association with breast density.ConclusionsOur findings revealed that both the distribution of tumor phenotype and breast density play specific and independent roles in each category of interval cancer. Further research is needed to understand the biological basis of the overrepresentation of triple-negative phenotype among predominantly fatty breasts in true interval cancers.

Variation in detection of ductal carcinoma in situ during screening mammography: a survey within the International Cancer Screening Network

BACKGROUND There is concern about detection of ductal carcinoma in situ (DCIS) in screening mammography. DCIS accounts for a substantial proportion of screen-detected lesions but its effect on breast cancer mortality is debated. The International Cancer Screening Network conducted a comparative analysis to determine variation in DCIS detection. PATIENTS AND METHODS Data were collected during 2004-2008 on number of screening examinations, detected breast cancers, DCIS cases and Globocan 2008 breast cancer incidence rates derived from national or regional cancer registers. We calculated screen-detection rates for breast cancers and DCIS. RESULTS Data were obtained from 15 screening settings in 12 countries; 7,176,050 screening examinations; 29,605 breast cancers and 5324 DCIS cases. The ratio between highest and lowest breast cancer incidence was 2.88 (95% confidence interval (CI) 2.76-3.00); 2.97 (95% CI 2.51-3.51) for detection of breast cancer; and 3.49 (95% CI 2.70-4.51) for detection of DCIS. CONCLUSIONS Considerable international variation was found in DCIS detection. This variation could not be fully explained by variation in incidence nor in breast cancer detection rates. It suggests the potential for wide discrepancies in management of DCIS resulting in overtreatment of indolent DCIS or undertreatment of potentially curable disease. Comprehensive cancer registration is needed to monitor DCIS detection. Efforts to understand discrepancies and standardise management may improve care.

Reduction in False-Positive Results after Introduction of Digital Mammography: Analysis from Four Population-based Breast Cancer Screening Programs in Spain

PURPOSE To evaluate the effect of the introduction of digital mammography on the recall rate, detection rate, false-positive rate, and rates of invasive procedures in a cohort of women from four population-based breast cancer screening programs in Spain. MATERIALS AND METHODS The study was approved by the ethics committee; informed consent was not required. A total of 242,838 mammograms (171,191 screen film [screen-film mammography group] and 71,647 digital [digital mammography group]) obtained in 103,613 women aged 45-69 years were included. False-positive results for any additional procedure and for invasive procedures, the breast cancer rate, and the positive predictive value in each group were compared by using Pearson χ(2) test. The effect of the mammographic technology used (screen-film or digital) on the false-positive results and cancer detection risk was evaluated with multivariate logistic regression models, adjusted according to womens and the screening programs characteristics and time trends. RESULTS The false-positive rate was higher for screen-film than for digital mammography (7.6% and 5.7%, respectively; P < .001). False-positive results after an invasive procedure were significantly higher for screen-film than for digital mammography (1.9% and 0.7%, respectively; P < .001). No significant differences were observed in the overall cancer detection rate between the two groups (0.45% and 0.43% in the screen-film and digital mammography groups, respectively; P = .59). The adjusted risk of a false-positive result was higher for screen-film than for digital mammography (odds ratio = 1.32). The adjusted risk was also lower for the digital mammography group when time trends were taken into account. CONCLUSION The lower false-positive risk with use of digital mammography should be taken into account when balancing the risks and benefits of breast cancer screening.

Effect of start age of breast cancer screening mammography on the risk of false-positive results.

OBJECTIVE To estimate the false-positive (FP) risk according to the start age of mammography screening (45-46 or 50-51 years). METHOD Data from eight regions of the Spanish breast cancer screening programme from 1990 to 2006 were included (1,565,364 women). Discrete time-hazard models were used to ascertain the effect of age and time-related, programme-related and personal variables on FP leading to any further procedure and to invasive procedures (FPI). In a subset we estimated the differential FP risk of starting screening at 45-46 years (175,656 women) or 50-51 (251,275). RESULTS A start age of 45-46 versus 50-51 years increased both FP (OR=1.20; 95%CI: 1.13-1.26) and FPI risks (OR=1.43 (95%CI: 1.18-1.73).Other factors increasing FP risk were premenopausal status (FP OR=1.26; 95%CI: 1.23-1.29 and FPI OR=1.22; 95%CI: 1.13-1.31), prior invasive procedures (FP OR=1.52; 95%CI: 1.47-1.57 and FPI (OR=2.08; 95%CI: 1.89-2.28) and family history (FP OR=1.16; 95%CI: 1.12-1.20 and FPI OR=1.26; 95%CI: 1.13-1.41). FP risk was increased by double reading (OR=1.36; 95%CI: 1.23-1.51) and FPI risk by double views (OR=1.34; 95%CI: 1.18-1.52). Both the cumulative FP and FPI risks were higher in women commencing screening at 45-46 years versus 50-51 years (33.30% versus 20.39% and 2.68% versus 1.76%). CONCLUSIONS Starting screening earlier increases the cumulative risk of FP and FPI.

Effect of false-positive results on reattendance at breast cancer screening programmes in Spain.

BACKGROUND Mammography is the only breast screening method, we are aware of today, which is able to reduce mortality from breast cancer. Nevertheless, this procedure carries an inherent risk of false-positive screening mammogram. The association between these results and reattendance at the next scheduled screening mammogram is controversial. The aim of this study was to examine the effect of a false-positive screening mammogram and womens characteristics on reattendance in eight regional population-based breast cancer screening programmes in Spain. METHODS This study included 1 383 032 women aged 44-67 years who were initially screened for breast cancer between 1990 and 2004. To investigate factors associated with reattendance, logistic regression models were used. RESULTS The mean age of women at first screening was 53.6 years (SD = 6.1 years). Of 120 800 women with a false-positive screening mammogram, 78.3% returned for a subsequent screening mammogram compared with 81.9% of those with a negative result (P < 0.001). Multivariate analysis showed that women with a false-positive result at first screening mammogram were less likely to reattend (OR = 0.71; 95% CI 0.70-0.73) and that the likelihood was lower in those who had undergone invasive additional tests (OR = 0.56; 95% CI 0.53-0.59). CONCLUSION A false-positive screening mammogram in the first screening negatively affected attendance at the subsequent screening. The results of this study could be useful to improve the screening process and to increase womens compliance.

International variation in management of screen-detected ductal carcinoma in situ of the breast

BACKGROUND Ductal carcinoma in situ (DCIS) incidence has grown with the implementation of screening and its detection varies across International Cancer Screening Network (ICSN) countries. The aim of this survey is to describe the management of screen-detected DCIS in ICSN countries and to evaluate the potential for treatment related morbidity. METHODS We sought screen-detected DCIS data from the ICSN countries identified during 2004-2008. We adopted standardised data collection forms and analysis and explored DCIS diagnosis and treatment processes ranging from pre-operative diagnosis to type of surgery and radiotherapy. RESULTS Twelve countries contributed data from a total of 15 screening programmes, all from Europe except the United States of America and Japan. Among women aged 50-69 years, 7,176,050 screening tests and 5324 screen-detected DCIS were reported. From 21% to 93% of DCIS had a pre-operative diagnosis (PO); 67-90% of DCIS received breast conservation surgery (BCS), and in 41-100% of the cases this was followed by radiotherapy; 6.4-59% received sentinel lymph node biopsy (SLNB) only and 0.8-49% axillary dissection (ALND) with 0.6% (range by programmes 0-8.1%) being node positive. Among BCS patients 35% received SLNB only and 4.8% received ALND. Starting in 2006, PO and SLNB use increased while ALND remained stable. SLNB and ALND were associated with larger size and higher grade DCIS lesions. CONCLUSIONS Variation in DCIS management among screened women is wide and includes lymph node surgery beyond what is currently recommended. This indicates the presence of varying levels of overtreatment and the potential for its reduction.