Treatment of patients with screen-detected colorectal cancer is less strenuous: a nationwide cohort study with long-term follow-up.

OBJECTIVE: During the last two decades, organised colorectal cancer (CRC) screening has been widely implemented. It remains to be established if screen-detected CRC (SD-CRC) is associated with reduced long-term requirements for treatment as compared with patients with non-screen-detected CRC (NSD-CRC). STUDY DESIGN AND METHODS: This nationwide cohort study evaluated differences in treatment and healthcare contacts from the date of diagnosis to two years after comparing patients with SD-CRC and NSD-CRC. Data were collected from national healthcare registers, including patients aged 50-75 years and diagnosed with CRC between January 1st 2014 and March 31st 2018. Analyses were stratified into UICC stages and adjusted for sex, 5-year age groups, type of cancer (colonic/rectal), and Charlson comorbidity index score to address healthy user bias. RESULTS: In total, 12,040 patients were included, 4708 with SD-CRC and 7332 with NSD-CRC. In patients with SD-CRC, the duration of hospitalisation and rate of emergency surgery were reduced by 38 % (relative risk [RR] = 0.62) and 66 % (RR = 0.34), respectively. Moreover, this group was characterised by a 75 % reduction in oncological outpatient visits (RR = 0.35) and a reduced number of treatments with chemotherapy (RR = 0.57) and radiotherapy (RR = 0.50). There were no significant differences between the two populations in the rates of metastasectomy and the number of contacts with primary healthcare providers. CONCLUSION: Compared to patients with NSD-CRC, patients with SD-CRC experience less hospitalisation and treatment within the first two years after diagnosis.

Validation of the Danish Colorectal Cancer Group (DCCG.dk) database - on behalf of the Danish Colorectal Cancer Group.

AIM: The aim of this study was to validate the clinical quality database of the Danish Colorectal Cancer Group. The validation is meant to focus on core data regarding staging of the disease, treatment provided, patient-related factors and key complications. METHOD: This was a database validation study assessing the completeness of the database and the accuracy of the data by re-entering core variables into an online module in a blinded fashion and comparing re-entered data with the original database data. A sample of 5% of patients from the years 2014-2017 was randomly selected. RESULTS: The sample of 936 patients was identified and data were re-entered. The completeness of the data retrieved was a median of 96%, 100% and 99% for preoperative, intra-operative and postoperative variables, respectively. The overall accuracy was a median of 95%. The least accurate variable was date of diagnosis (50% perfect agreement), with agreement rising to 96% when near matches defined as correct date ± 30 days were included. Intra-operative variables were of high quality, as were data on surgical complications including anastomotic leakage, where agreement was 97%. CONCLUSION: This was the first major validation of the Danish Colorectal Cancer Group's database. Overall, the completeness and quality of data were high, but the validation process also identified weaknesses, which can be crucial for future users to acknowledge and consider.

Referral population studies underestimate differences between human papillomavirus assays in primary cervical screening.

OBJECTIVE: We studied how representative cytologically abnormal women ("referral populations") are with respect to uncovering differences between human papillomavirus (HPV) assays in the primary screening where most women are cytologically normal. METHODS: A total of 4997 women were tested with SurePath® cytology, and Hybrid Capture 2 (HC2), cobas, CLART and APTIMA HPV assays. Women with positive test results were offered a follow-up. For all detected HPV infections and HPV-positive high-grade cervical intraepithelial neoplasia (≥CIN2), we studied the distributions of assay-specific signal strengths in the baseline samples as documented by the assays' automatically generated reports. We calculated the likelihood of test result discordance as the proportion of HPV-positive samples that were not confirmed by all four assays. RESULTS: Median signal strengths for HPV infections were weaker in normal than abnormal cytology (P<.001, adjusted for women's age, multiple infections and the reason for taking the sample). For HC2, they were RLU/CO 11.0 (interquartile range, IQR: 3.3-52.8) vs 124.2 (IQR: 22.8-506.9), respectively; for cobas, Ct 33.5 (IQR: 29.6-37.5) vs 26.9 (IQR: 23.7-31.3), respectively; for APTIMA, S/CO 10.2 (IQR: 5.8-11.3) vs 11.1 (IQR: 9.4-15.5), respectively. Similar patterns were observed for HPV-positive ≥CIN2. The four HPV assays more frequently returned discordant test results in normal than in abnormal cytology. Relative frequency of discordance in detecting HPV infections was 0.39 (95% confidence interval: 0.33-0.48) for abnormal vs normal cytology. CONCLUSIONS: These data suggest that referral population studies, by not including sufficient numbers of cytology normal women, underestimate the differences between HPV assays that would become apparent in primary screening.

Tumour size distribution in mammography screening.

Many mammography screening programmes have not been able to show higher percentages of small invasive cancers detected at subsequent screens than at initial screens. This has been a matter of serious concern as it contradicts the very theory of screening. Based on data from the county of Fyn, Denmark we evaluated the distribution based on point estimates, as well as on the entire tumour size distribution. The programme changed the amount of tumours less than 15 or 20 mm, but did not change the amount of tumours less than 10 mm. We evaluated the entire tumour size distribution and found that screen number was the only significant factor, implying that the number of screens changed the tumour size distribution. We recommend that the entire tumour size distribution is used to evaluate the ability of a programme to detect small breast cancers, instead of only point estimates as has previously been the practice.

The impact of mammographic screening on breast cancer mortality in Europe: a review of trend studies.

OBJECTIVE: Analysing trends in population breast cancer mortality statistics appears a simple method of estimating the effectiveness of mammographic screening programmes. We reviewed such studies of population-based screening in Europe to assess their value. METHODS: A literature review identified 17 papers, of which 12 provided quantitative estimates of the impact of screening. Due to differences in comparisons and outcome measures, no pooled estimate of effectiveness was calculated. RESULTS: Comparisons included breast cancer mortality before and after the introduction of screening, trends in early and late starting areas and trends in age groups affected and unaffected by screening. Studies that calculated the percentage annual change after the start of screening found reductions of 1-9% per year (1%, 2.3-2.8% and 9% for those with adequate follow-up). Of studies that compared mortality in time periods before and after introduction of screening, three single country studies all had adequate follow-up and estimated mortality reductions ranging from 28% to 36%. Limitations of studies of population mortality rates include the inability to exclude deaths in women with breast cancer diagnosed before invitation to screening, diluting any observable impact of screening, and the gradual implementation of screening in a country or region. CONCLUSIONS: Although analysing population breast cancer mortality rates over time can be a first step in examining changes following the introduction of screening, this method is of limited value for assessment of screening impact. Other methods and individual data are necessary to properly quantify the effect.

Breast cancer incidence after the start of mammography screening in Denmark.

Mammography screening may lead to overdiagnosis of asymptomatic breast cancers, that would otherwise not have given rise to clinical symptoms. This aspect was studied in three regional screening programmes in Denmark, which started in Copenhagen municipality, Fyn county, and Frederiksberg municipality in 1991, 1993, and 1994, respectively. In these regions, we compared time trends in incidence of invasive breast cancer with the rest of Denmark. Since the number of clinical mammograms was relatively low, it was reasonable to assume that the breast cancer incidence outside the three screening regions represented the incidence of a population with low-intensity opportunistic screening. In Copenhagen and Fyn, a prevalence peak in incidence was seen during the first invitation round. During the subsequent invitation rounds, the incidence dropped to a level in line with the incidence expected without screening. The pattern was different in the small municipality of Frederiksberg, where the sensitivity was low during the first invitation round. Inclusion of screen-detected ductal carcinoma in situ cases did not change these results. The experiences from Copenhagen and Fyn show that organised mammography screening can operate without overdiagnosis of breast cancer.