Screening with mammography uses X-ray imaging to find breast cancer before a lump can be felt. The goal is to treat cancer earlier, when a cure is more likely. The review includes seven trials that involved 600,000 women in the age range 39 to 74 years who were randomly assigned to receive screening mammograms or not. The studies which provided the most reliable information showed that screening did not reduce breast cancer mortality. Studies that were potentially more biased (less carefully done) found that screening reduced breast cancer mortality. However, screening will result in some women getting a cancer diagnosis even though their cancer would not have led to death or sickness. Currently, it is not possible to tell which women these are, and they are therefore likely to have breasts or lumps removed and to receive radiotherapy unnecessarily. If we assume that screening reduces breast cancer mortality by 15% after 13 years of follow-up and that overdiagnosis and overtreatment is at 30%, it means that for every 2000 women invited for screening throughout 10 years, one will avoid dying of breast cancer and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress including anxiety and uncertainty for years because of false positive findings.
Women invited to screening should be fully informed of both the benefits and harms. To help ensure that the requirements for informed choice for women contemplating whether or not to attend a screening programme can be met, we have written an evidence-based leaflet for lay people that is available in several languages on www.cochrane.dk. Because of substantial advances in treatment and greater breast cancer awareness since the trials were carried out, it is likely that the absolute effect of screening today is smaller than in the trials. Recent observational studies show more overdiagnosis than in the trials and very little or no reduction in the incidence of advanced cancers with screening.

/pdf/screening-for-breast-cancer-with-mammography-36k7l5kzia.pdf

Screening for breast cancer with mammography.

Background There are limited data from randomized trials regarding whether volume-based, low-dose computed tomographic (CT) screening can reduce lung-cancer mortality among male former and...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1911793?articleTools=true

Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial

https://www.pure.ed.ac.uk/ws/files/8378925/The_benefits_and_harms_of_breast_cancer_screening.pdf

The benefits and harms of breast cancer screening: an independent review

Importance Breast cancer is a leading cause of premature mortality among US women. Early detection has been shown to be associated with reduced breast cancer morbidity and mortality. Objective To update the American Cancer Society (ACS) 2003 breast cancer screening guideline for women at average risk for breast cancer. Process The ACS commissioned a systematic evidence review of the breast cancer screening literature to inform the update and a supplemental analysis of mammography registry data to address questions related to the screening interval. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. Evidence Synthesis Screening mammography in women aged 40 to 69 years is associated with a reduction in breast cancer deaths across a range of study designs, and inferential evidence supports breast cancer screening for women 70 years and older who are in good health. Estimates of the cumulative lifetime risk of false-positive examination results are greater if screening begins at younger ages because of the greater number of mammograms, as well as the higher recall rate in younger women. The quality of the evidence for overdiagnosis is not sufficient to estimate a lifetime risk with confidence. Analysis examining the screening interval demonstrates more favorable tumor characteristics when premenopausal women are screened annually vs biennially. Evidence does not support routine clinical breast examination as a screening method for women at average risk. Recommendations The ACS recommends that women with an average risk of breast cancer should undergo regular screening mammography starting at age 45 years (strong recommendation). Women aged 45 to 54 years should be screened annually (qualified recommendation). Women 55 years and older should transition to biennial screening or have the opportunity to continue screening annually (qualified recommendation). Women should have the opportunity to begin annual screening between the ages of 40 and 44 years (qualified recommendation). Women should continue screening mammography as long as their overall health is good and they have a life expectancy of 10 years or longer (qualified recommendation). The ACS does not recommend clinical breast examination for breast cancer screening among average-risk women at any age (qualified recommendation). Conclusions and Relevance These updated ACS guidelines provide evidence-based recommendations for breast cancer screening for women at average risk of breast cancer. These recommendations should be considered by physicians and women in discussions about breast cancer screening.

/pdf/breast-cancer-screening-for-women-at-average-risk-2015-2zpe99a39l.pdf

Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update From the American Cancer Society

textBACKGROUND: Screening for prostate cancer advances the time of diagnosis
 (lead time) and detects cancers that would not have been diagnosed in the
 absence of screening (overdetection). Both consequences have considerable
 impact on the net benefits of screening. METHODS: We developed simulation
 models based on results of the Rotterdam section of the European
 Randomized Study of Screening for Prostate Cancer (ERSPC), which enrolled
 42,376 men and in which 1498 cases of prostate cancer were identified, and
 on baseline prostate cancer incidence and stage distribution data. The
 models were used to predict mean lead times, overdetection rates, and
 ranges (corresponding to approximate 95% confidence intervals) associated
 with different screening programs. RESULTS: Mean lead times and rates of
 overdetection depended on a man's age at screening. For a single screening
 test at age 55, the estimated mean lead time was 12.3 years (range =
 11.6-14.1 years) and the overdetection rate was 27% (range = 24%-37%); at
 age 75, the estimates were 6.0 years (range = 5.8-6.3 years) and 56%
 (range = 53%-61%), respectively. For a screening program with a 4-year
 screening interval from age 55 to 67, the estimated mean lead time was
 11.2 years (range = 10.8-12.1 years), and the overdetection rate was 48%
 (range = 44%-55%). This screening program raised the lifetime risk of a
 prostate cancer diagnosis from 6.4% to 10.6%, a relative increase of 65%
 (range = 56%-87%). In annual screening from age 55 to 67, the estimated
 overdetection rate was 50% (range = 46%-57%) and the lifetime prostate
 cancer risk was increased by 80% (range = 69%-116%). Extending annual or
 quadrennial screening to the age of 75 would result in at least two cases
 of overdetection for every clinically relevant cancer detected.
 CONCLUSIONS: These model-based lead-time estimates support a prostate
 cancer screening interval of more than 1 year.

/pdf/lead-times-and-overdetection-due-to-prostate-specific-m0qok7a4pu.pdf

Lead times and overdetection due to prostate-specific antigen screening: estimates from the European Randomized Study of Screening for Prostate Cancer.

Mammographic screening for women aged 50-70 is effective in reducing breast cancer mortality, but the impact on quality of life and the attainable mortality reduction remain t o be discussed. The consequences of expanding screening programmes to include women in other age groups are uncertain. We have predicted the effects and costs for 5 popular screening variants, differing in age group and screening interval, on the basis of our analysis of the Dutch screening trials and of the reported mortality reductions in other trials. We have also investigated the influence of a large number of uncertain factors. Screening for women aged 50 and over with a 2- or 3-year interval is very cost-effective and will result in reductions of respectively 16% or 10% in breast cancer mortality in a real population. Variation of most variables keeps the cost-effectiveness (CE) ratio limited to the range of US $3,000 to 5,000 per life-year gained. A 2- to 3-fold change in CE ratio would only occur if the extreme estimates of mortality reduction in the Swedish screening trials were applied. The impact on quality of life (QoL) is limited: for the 2-yearly screening policy for women aged 50-70, the cost per Quality-Adjusted Life-Year (QALY) gained is 4,050, whereas the cost per life-year gained is US $3,825. The CE ratio for 2-yearly screening of women aged 40-70 is 5,400, but the additional cost per additional life-year gained is US $35,000. It would be preferable by far to extend the screening programme to women over the age of 70 or to shorten the screening interval for women aged 50-70. Screening performances, the demand for mammograms outside screening and the possibility of a survival improvement irrespective of screening have a strong impact on QoL and CE.

Breast cancer screening and cost-effectiveness; policy alternatives, quality of life considerations and the possible impact of uncertain factors.

The MISCAN-COLON simulation model for the evaluation of colorectal cancer screening

Data from the screening programme in British Columbia are used to test hypotheses about the natural history of cervical cancer, especially about progression and regression of preclinical lesions (dysplasia and carcinoma in situ). Three models are considered. A model without regression does not give an adequate fit of the data (P less than 0.001), and results in an implausible estimate of 33 years for the mean duration of pre-invasive lesions. A model with an equal regression rate at all ages still does not result in a good reproduction of the data. A good fit is achieved for a model with different regression rates in lesions that develop under and over age 34. Under age 34, 84% of the new lesions will regress spontaneously, with a 95% confidence interval of 76-92% regression. Over age 34, we estimate that 40% of the new lesions will regress. The average duration of dysplasia + CIS is 11.8 years, and the sensitivity of the Pap-smear is 80%. It is concluded that a considerable proportion of pre-invasive lesions in young women do not progress. The findings about progression and duration of pre-invasive lesions do not support the still prevailing tendency of frequently making Pap smears in young women.

Epidemiological evidence for age-dependent regression of pre-invasive cervical cancer.

OBJECTIVE: To elucidate the conditions in which mass treatment with ivermectin reduces the transmission of Onchocerca volvulus sufficiently to eliminate infection from an African community. METHODS: ONCHOSIM, a microsimulation model for onchocerciasis transmission, was used to explore the implications of different treatment intervals, coverage levels and precontrol endemicities for the likelihood of elimination. FINDINGS: Simulations suggested that control strategies based exclusively on ivermectin mass treatments could eliminate onchocerciasis. The duration of treatment required to eliminate infection depended heavily on the treatment programme and precontrol endemicity. In areas with medium to high levels of infection, annual mass treatments with 65% coverage for at least 25 years were necessary. Model predictions suggested that durations exceeding 35 years would be required if there were much heterogeneity in exposure to vector bites and, consequently, wide individual variation in microfilaria counts. If the treatment interval were reduced from 12 to 6 months the time for completion of the programme could be more than halved and elimination could be accomplished in areas of hyperendemicity, provided that the effects of each treatment would be the same as with annual treatments. However, it was doubtful whether high coverage levels could be sustained long enough to achieve worldwide eradication. CONCLUSION: Elimination of onchocerciasis from most endemic foci in Africa appears to be possible. However, the requirements in terms of duration, coverage, and frequency of treatment may be prohibitive in highly endemic areas.

/pdf/can-ivermectin-mass-treatments-eliminate-onchocerciasis-in-1b8vrfa5tf.pdf

Can ivermectin mass treatments eliminate onchocerciasis in Africa

https://repub.eur.nl/pub/53245/OA_1-s2.0-0001706X9190015C.pdf

G.J. van Oortmarssen

Papers

Breast cancer screening and cost-effectiveness; policy alternatives, quality of life considerations and the possible impact of uncertain factors.

The MISCAN-COLON simulation model for the evaluation of colorectal cancer screening

Epidemiological evidence for age-dependent regression of pre-invasive cervical cancer.

Can ivermectin mass treatments eliminate onchocerciasis in Africa

The reproductive lifespan of Onchocerca volvulus in West African savanna.