Quality of life of women with a screen-detected versus clinically detected breast cancer in the Netherlands: a prospective cohort study.

PURPOSE: Breast cancer (BC) screening enables early detection of BC, which may lead to improved quality of life (QoL). We aim to compare QoL between women with a screen-detected and clinically detected BC in the Netherlands. METHODS: We used data from the 'Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaluation' (UMBRELLA) between October 2013 and March 2022. Patients were categorized as screen-detected or clinically detected. We analysed three questionnaires, namely EORTC QLQ C-30, BR23, and HADS (Hospital Anxiety and Depression Scale) completed by BC patients shortly after diagnosis (T1) and one-year after treatment (T2). Independent t-tests were performed to compare QoL average differences between the two groups. Bonferroni-corrected p-value significance threshold of 0.00057 was used. The magnitude of differences was calculated using Cohen's d. The clinical relevance of QLQ-C30 differences was assessed based on interpretation guideline of EORTC-QLQ-C30 results. RESULTS: After applying inclusion and exclusion criteria, there were 691 women with screen-detected BC and 480 with clinically detected BC. Generally, screen-detected BC patients reported a better QoL. At T1, their average QLQ-C30 summary score was higher (86.1) than clinically detected BC patients (83.0) (p < 0.0001). Cohen's d for all items ranged between 0.00 and 0.39. A few QLQ-C30 score differences were clinically relevant, indicating better outcomes in emotional functioning, general health, constipation, and fatigue for women with screen-detected BC. CONCLUSIONS: In the Netherlands, women with screen-detected BC reported statistically significant and better QoL than women with clinically detected BC. However, clinical relevance of the differences is limited.

This study compares the quality of life (QoL) of women with breast cancer (BC) detected through screening versus through clinical detection in the Netherlands. BC screening aims to detect cancer early, potentially improving QoL. We analysed data from the UMBRELLA cohort, focusing on QoL questionnaires filled out shortly after diagnosis and one year after treatment. Results showed that women with screen-detected BC generally reported better QoL than those with clinically detected BC. For example, they had higher QLQ-C30 summary scores and several other QLQ-C30 scales and items, indicating better emotional functioning, better general health, less constipation, and less fatigue symptom. We also found that the differences in QoL are larger at one year after treatment. However, while statistically significant, the differences in QoL between the two groups were either trivial or small and may have limited clinical relevance. This study sheds light on the potential impact of mode of detection on the QoL of women with BC.

Modelling the cost-effectiveness of a newborn hearing screening programme; usability and pitfalls.

OBJECTIVE: The EUSCREEN project concerns the study of European vision and hearing screening programmes. Part of the project was the development of a cost-effectiveness model to analyse such programmes. We describe the development and usability of an online tool to enable stakeholders to design, analyse or modify a newborn hearing screening (NHS) programme. DESIGN: Data from literature, from existing NHS programmes, and observations by users were used to develop and refine the tool. Required inputs include prevalence of the hearing impairment, test sequence and its timing, attendance, sensitivity, and specificity of each screening step. Outputs include the number of cases detected and the costs of screening and diagnostics. STUDY SAMPLE: Eleven NHS programmes with reliable data. RESULTS: Three analyses are presented, exploring the effect of low attendance, number of screening steps, testing in the maternity ward, or screening at a later age, on the benefits and costs of the programme. Knowledge of the epidemiology of a staged screening programme is crucial when using the tool. CONCLUSIONS: This study presents a tool intended to aid stakeholders to design a new or analyse an existing hearing screening programme in terms of benefits and costs.

Cumulative risks of false positive recall and screen-detected breast cancer after multiple screening examinations.

Women tend to make a decision about participation in breast cancer screening and adhere to this for future invitations. Therefore, our study aimed to provide high-quality information on cumulative risks of false-positive (FP) recall and screen-detected breast cancer over multiple screening examinations. Individual Dutch screening registry data (2005-2018) were gathered on subsequent screening examinations of 92 902 women age 49 to 51 years in 2005. Survival analyses were used to calculate cumulative risks of a FP and a true-positive (TP) result after seven examinations. Data from 66 472 women age 58 to 59 years were used to extrapolate to 11 examinations. Participation, detection and additional FP rates were calculated for women who previously received FP results compared to women with true negative (TN) results. After 7 examinations, the cumulative risk of a TP result was 3.7% and the cumulative risk of a FP result was 9.1%. After 11 examinations, this increased to 7.1% and 13.5%, respectively. Following a FP result, participation was lower (71%-81%) than following a TN result (>90%). In women with a FP result, more TP results (factor 1.59 [95% CI: 1.44-1.72]), more interval cancers (factor 1.66 [95% CI: 1.41-1.91]) and more FP results (factor 1.96 [95% CI: 1.87-2.05]) were found than in women with TN results. In conclusion, due to a low recall rate in the Netherlands, the cumulative risk of a FP recall is relatively low, while the cumulative risk of a TP result is comparable. Breast cancer diagnoses and FP results were more common in women with FP results than in women with TN results, while participation was lower.

Finding the optimal mammography screening strategy: A cost-effectiveness analysis of 920 modelled strategies.

Breast cancer screening policies have been designed decades ago, but current screening strategies may not be optimal anymore. Next to that, screening capacity issues may restrict feasibility. This cost-effectiveness study evaluates an extensive set of breast cancer screening strategies in the Netherlands. Using the Microsimulation Screening Analysis-Breast (MISCAN-Breast) model, the cost-effectiveness of 920 breast cancer screening strategies with varying starting ages (40-60), stopping ages (64-84) and intervals (1-4 years) were simulated. The number of quality adjusted life years (QALYs) gained and additional net costs (in €) per 1000 women were predicted (3.5% discounted) and incremental cost-effectiveness ratios (ICERs) were calculated to compare screening scenarios. Sensitivity analyses were performed using different assumptions. In total, 26 strategies covering all four intervals were on the efficiency frontier. Using a willingness-to-pay threshold of €20 000/QALY gained, the biennial 40 to 76 screening strategy was optimal. However, this strategy resulted in more overdiagnoses and false positives, and required a high screening capacity. The current strategy in the Netherlands, biennial 50 to 74 years, was dominated. Triennial screening in the age range 44 to 71 (ICER 9364) or 44 to 74 (ICER 11144) resulted in slightly more QALYs gained and lower costs than the current Dutch strategy. Furthermore, these strategies were estimated to require a lower screening capacity. Findings were robust when varying attendance and effectiveness of treatment. In conclusion, switching from biennial to triennial screening while simultaneously lowering the starting age to 44 can increase benefits at lower costs and with a minor increase in harms compared to the current strategy.

The potential of breast cancer screening in Europe.

Currently, all European countries offer some form of breast cancer screening. Nevertheless, disparities exist in the status of implementation, attendance and the extent of opportunistic screening. As a result, breast cancer screening has not yet reached its full potential. We examined how many breast cancer deaths could be prevented if all European countries would biennially screen all women aged 50 to 69 for breast cancer. We calculated the number of breast cancer deaths already prevented due to screening as well as the number of breast cancer deaths which could be additionally prevented if the total examination coverage (organised plus opportunistic) would reach 100%. The calculations are based on total examination coverage in women aged 50 to 69, the annual number of breast cancer deaths for women aged 50 to 74 and the maximal possible mortality reduction from breast cancer, assuming similar effectiveness of organised and opportunistic screening. The total examination coverage ranged from 49% (East), 62% (West), 64% (North) to 69% (South). Yearly 21 680 breast cancer deaths have already been prevented due to mammography screening. If all countries would reach 100% examination coverage, 12 434 additional breast cancer deaths could be prevented annually, with the biggest potential in Eastern Europe. With maximum coverage, 23% of their breast cancer deaths could be additionally prevented, while in Western Europe it could be 21%, in Southern Europe 15% and in Northern Europe 9%. Our study illustrates that by further optimising screening coverage, the number of breast cancer deaths in Europe can be lowered substantially.

Effects of cancer screening restart strategies after COVID-19 disruption.

BACKGROUND: Many breast, cervical, and colorectal cancer screening programmes were disrupted due to the COVID-19 pandemic. This study aimed to estimate the effects of five restart strategies after the disruption on required screening capacity and cancer burden. METHODS: Microsimulation models simulated five restart strategies for breast, cervical, and colorectal cancer screening. The models estimated required screening capacity, cancer incidence, and cancer-specific mortality after a disruption of 6 months. The restart strategies varied in whether screens were caught up or not and, if so, immediately or delayed, and whether the upper age limit was increased. RESULTS: The disruption in screening programmes without catch-up of missed screens led to an increase of 2.0, 0.3, and 2.5 cancer deaths per 100 000 individuals in 10 years in breast, cervical, and colorectal cancer, respectively. Immediately catching-up missed screens minimised the impact of the disruption but required a surge in screening capacity. Delaying screening, but still offering all screening rounds gave the best balance between required capacity, incidence, and mortality. CONCLUSIONS: Strategies with the smallest loss in health effects were also the most burdensome for the screening organisations. Which strategy is preferred depends on the organisation and available capacity in a country.

Cost-Effectiveness of Neonatal Hearing Screening Programs: A Micro-Simulation Modeling Analysis.

OBJECTIVES: Early detection of neonatal hearing impairment moderates the negative effects on speech and language development. Universal neonatal hearing screening protocols vary in tests used, timing of testing and the number of stages of screening. This study estimated the cost-effectiveness of various protocols in the preparation of implementation of neonatal hearing screening in Albania. DESIGN: A micro-simulation model was developed using input on demography, natural history of neonatal hearing impairment, screening characteristics and treatment. Parameter values were derived from a review of the literature and expert opinion. We simulated multiple protocols using otoacoustic emissions (OAE) and automated auditory brainstem response (aABR), varying the test type, timing and number of stages. Cost-effectiveness was analyzed over a life-time horizon. RESULTS: The two best protocols for well infants were OAE followed by aABR (i.e., two-stage OAE-aABR) testing in the maternity ward and single-aABR testing. Incremental cost-effectiveness ratios were €4181 and €78,077 per quality-adjusted life-year gained, respectively. Single-aABR screening led to more cases being detected compared to a two-stage screening program. However, it also resulted in higher referral rates, which increased the total costs of diagnostics. Multi-staged screening decreased referral rates but may increase the number of missed cases due to false-negative test results and nonattendance. CONCLUSIONS: Only the 2-stage OAE-aABR (maternity ward) protocol was below the willingness-to-pay threshold of €10,413 for Albania, as suggested by the World Health Organization, and was found to be cost-effective. This study is among the few to assess neonatal hearing screening programs over a life-time horizon and the first to predict the cost-effectiveness of multiple screening scenarios.

Risk stratification in breast cancer screening: Cost-effectiveness and harm-benefit ratios for low-risk and high-risk women.

In mammography screening programmes, women are screened according to a one-size-fits-all principle. Tailored screening, based on risk levels, may lead to a better balance of benefits and harms. With microsimulation modelling, we determined optimal mammography screening strategies for women at lower (relative risk [RR] 0.75) and higher (RR 1.8) than average risk of breast cancer, eligible for screening, using the incremental cost-effectiveness ratio (ICER) of current uniform screening in the Netherlands (biennial [B] 50-74) as a threshold ICER. Strategies varied by interval (annual [A], biennial, triennial [T]) and age range. The number of life-years gained (LYG), breast cancer deaths averted, overdiagnosed cases, false-positive mammograms, ICERs and harm-benefit ratios were calculated. Optimal risk-based screening scenarios, below the threshold ICER of €8883/LYG, were T50-71 (€7840/LYG) for low-risk and B40-74 (€6062/LYG) for high-risk women. T50-71 screening in low-risk women resulted in a 33% reduction in false-positive findings, a similar reduction in costs and improved harm-benefit ratios compared to the current screening schedule. B40-74 in high-risk women led to an increase in screening benefit, compared to current B50-74 screening, but a relatively higher increase in false-positive findings. In conclusion, optimal screening consisted of a longer interval and lower stopping age than current uniform screening for low-risk women, and a lower starting age for high-risk women. Extending the interval for women at lower risk from biennial to triennial screening reduced harms and costs while maintaining most of the screening benefit.

MRI versus mammography for breast cancer screening in women with familial risk (FaMRIsc): a multicentre, randomised, controlled trial.

BACKGROUND: Approximately 15% of all breast cancers occur in women with a family history of breast cancer, but for whom no causative hereditary gene mutation has been found. Screening guidelines for women with familial risk of breast cancer differ between countries. We did a randomised controlled trial (FaMRIsc) to compare MRI screening with mammography in women with familial risk. METHODS: In this multicentre, randomised, controlled trial done in 12 hospitals in the Netherlands, women were eligible to participate if they were aged 30-55 years and had a cumulative lifetime breast cancer risk of at least 20% because of a familial predisposition, but were BRCA1, BRCA2, and TP53 wild-type. Participants who were breast-feeding, pregnant, had a previous breast cancer screen, or had a previous a diagnosis of ductal carcinoma in situ were eligible, but those with a previously diagnosed invasive carcinoma were excluded. Participants were randomly allocated (1:1) to receive either annual MRI and clinical breast examination plus biennial mammography (MRI group) or annual mammography and clinical breast examination (mammography group). Randomisation was done via a web-based system and stratified by centre. Women who did not provide consent for randomisation could give consent for registration if they followed either the mammography group protocol or the MRI group protocol in a joint decision with their physician. Results from the registration group were only used in the analyses stratified by breast density. Primary outcomes were number, size, and nodal status of detected breast cancers. Analyses were done by intention to treat. This trial is registered with the Netherlands Trial Register, number NL2661. FINDINGS: Between Jan 1, 2011, and Dec 31, 2017, 1355 women provided consent for randomisation and 231 for registration. 675 of 1355 women were randomly allocated to the MRI group and 680 to the mammography group. 218 of 231 women opting to be in a registration group were in the mammography registration group and 13 were in the MRI registration group. The mean number of screening rounds per woman was 4·3 (SD 1·76). More breast cancers were detected in the MRI group than in the mammography group (40 vs 15; p=0·0017). Invasive cancers (24 in the MRI group and eight in the mammography group) were smaller in the MRI group than in the mammography group (median size 9 mm [5-14] vs 17 mm [13-22]; p=0·010) and less frequently node positive (four [17%] of 24 vs five [63%] of eight; p=0·023). Tumour stages of the cancers detected at incident rounds were significantly earlier in the MRI group (12 [48%] of 25 in the MRI group vs one [7%] of 15 in the mammography group were stage T1a and T1b cancers; one (4%) of 25 in the MRI group and two (13%) of 15 in the mammography group were stage T2 or higher; p=0·035) and node-positive tumours were less frequent (two [11%] of 18 in the MRI group vs five [63%] of eight in the mammography group; p=0·014). All seven tumours stage T2 or higher were in the two highest breast density categories (breast imaging reporting and data system categories C and D; p=0·0077) One patient died from breast cancer during follow-up (mammography registration group). INTERPRETATION: MRI screening detected cancers at an earlier stage than mammography. The lower number of late-stage cancers identified in incident rounds might reduce the use of adjuvant chemotherapy and decrease breast cancer-related mortality. However, the advantages of the MRI screening approach might be at the cost of more false-positive results, especially at high breast density. FUNDING: Dutch Government ZonMw, Dutch Cancer Society, A Sister's Hope, Pink Ribbon, Stichting Coolsingel, J&T Rijke Stichting.

Cost-effectiveness of surveillance schedules in older adults with non-muscle-invasive bladder cancer.

OBJECTIVE: To estimate the cost-effectiveness of surveillance schedules for non-muscle-invasive bladder cancer (NMIBC) amongst older adults. PATIENTS AND METHODS: We developed a MIcrosimulation SCreening ANalysis (MISCAN) microsimulation model to compare the cost-effectiveness of various surveillance schedules (every 3 months to every 24 months, for 2, 5 or 10 years or lifetime) for older adults (aged 65-85 years) with NMIBC. For each surveillance schedule we calculated total costs per patient and the number of quality adjusted life-years (QALYs) gained. Incremental cost-effectiveness ratios (ICERs), as incremental costs per QALY gained, were calculated using a 3% discount. RESULTS: As age increased, the number of QALYs gained per patient decreased substantially. Surveillance of patients aged 65 years resulted in 2-7 QALYs gained, whereas surveillance at age 85 years led to <1 QALY gained. The total costs of the surveillance schedules also decreased as age increased. The ICER of 6-monthly surveillance at age 65 years for lifetime was $4999 (American dollars)/QALY gained. Amongst patients aged >75 years, the incremental yield of QALY gains for any increase in surveillance frequency and/or duration was quite modest (<2 QALYs gained). CONCLUSION: With increasing age, surveillance for recurrences leads to substantially fewer QALYs gained. These data support age-specific surveillance recommendations for patients treated for NMIBC.

Summary statement on screening for prostate cancer in Europe.

The European Randomised Study of Screening for Prostate Cancer (ERSPC) showed that Prostate-Specific Antigen (PSA) based screening results in a significant prostate cancer mortality reduction. Although there are concerns on overdiagnosis and overtreatment, it has been shown that the benefits can outweigh the harms if screening is stopped in older ages to prevent overdiagnosis. A limited screening program (for example screening at ages 55-59 years), including active surveillance for men with low-risk tumors, can even be cost-saving, compared with testing in an opportunistic setting in the wrong ages, as currently in Europe. Further improvements are expected in the use of active surveillance and in discrimination between indolent and significant disease due to new biomarkers and magnetic resonance imaging. However, these future developments are no reason to postpone feasibility studies of high-quality PSA screening and reduce opportunistic testing at old ages.

Comparative effectiveness of prostate cancer screening between the ages of 55 and 69 years followed by active surveillance.

BACKGROUND: Because of the recent grade C draft recommendation by the US Preventive Services Task Force (USPSTF) for prostate cancer screening between the ages of 55 and 69 years, there is a need to determine whether this could be cost-effective in a US population setting. METHODS: This study used a microsimulation model of screening and active surveillance (AS), based on data from the European Randomized Study of Screening for Prostate Cancer and the Surveillance, Epidemiology, and End Results Program, for the natural history of prostate cancer and Johns Hopkins AS cohort data to inform the probabilities of referral to treatment during AS. A cohort of 10 million men, based on US life tables, was simulated. The lifetime costs and effects of screening between the ages of 55 and 69 years with different screening frequencies and AS protocols were projected, and their cost-effectiveness was determined. RESULTS: Quadrennial screening between the ages of 55 and 69 years (55, 59, 63, and 67 years) with AS for men with low-risk cancers (ie, those with a Gleason score of 6 or lower) and yearly biopsies or triennial biopsies resulted in an incremental cost per quality-adjusted life-year (QALY) of $51,918 or $69,380, respectively. Most policies in which screening was followed by immediate treatment were dominated. In most sensitivity analyses, this study found a policy with which the cost per QALY remained below $100,000. CONCLUSIONS: Prostate-specific antigen-based prostate cancer screening in the United States between the ages of 55 and 69 years, as recommended by the USPSTF, may be cost-effective at a $100,000 threshold but only with a quadrennial screening frequency and with AS offered to all low-risk men. Cancer 2018;124:507-13. © 2017 American Cancer Society.

The efficacy of prostate-specific antigen screening: Impact of key components in the ERSPC and PLCO trials.

BACKGROUND: The European Randomized Study of Screening for Prostate Cancer (ERSPC) demonstrated that prostate-specific antigen (PSA) screening significantly reduced prostate cancer mortality (rate ratio, 0.79; 95% confidence interval, 0.69-0.91). The US Prostate, Lung, Colorectal, and Ovarian (PLCO) trial indicated no such reduction but had a wide 95% CI (rate ratio for prostate cancer mortality, 1.09; 95% CI, 0.87-1.36). Standard meta-analyses are unable to account for key differences between the trials that can impact the estimated effects of screening and the trials' point estimates. METHODS: The authors calibrated 2 microsimulation models to individual-level incidence and mortality data from 238,936 men participating in the ERSPC and PLCO trials. A cure parameter for the underlying efficacy of screening was estimated by the models separately for each trial. The authors changed step-by-step major known differences in trial settings, including enrollment and attendance patterns, screening intervals, PSA thresholds, biopsy receipt, control arm contamination, and primary treatment, to reflect a more ideal protocol situation and differences between the trials. RESULTS: Using the cure parameter estimated for the ERSPC, the models projected 19% to 21% and 6% to 8%, respectively, prostate cancer mortality reductions in the ERSPC and PLCO settings. Using this cure parameter, the models projected a reduction of 37% to 43% under annual screening with 100% attendance and biopsy compliance and no contamination. The cure parameter estimated for the PLCO trial was 0. CONCLUSIONS: The observed cancer mortality reduction in screening trials appears to be highly sensitive to trial protocol and practice settings. Accounting for these differences, the efficacy of PSA screening in the PLCO setting is not necessarily inconsistent with ERSPC results. Cancer 2018;124:1197-206. © 2017 American Cancer Society.

Detection and interval cancer rates during the transition from screen-film to digital mammography in population-based screening.

BACKGROUND: Between 2003 and 2010 digital mammography (DM) gradually replaced screen-film mammography (SFM) in the Dutch breast cancer screening programme (BCSP). Previous studies showed increases in detection rate (DR) after the transition to DM. However, national interval cancer rates (ICR) have not yet been reported. METHODS: We assessed programme sensitivity and specificity during the transition period to DM, analysing nationwide data on screen-detected and interval cancers. Data of 7.3 million screens in women aged 49-74, between 2004 and 2011, were linked to the Netherlands Cancer Registry to obtain data on interval cancers. Age-adjusted DRs, ICRs and recall rates (RR) per 1000 screens and programme sensitivity and specificity were calculated by year, age and screening modality. RESULTS: 41,662 screen-detected and 16,160 interval cancers were analysed. The DR significantly increased from 5.13 (95% confidence interval (CI):5.00-5.30) in 2004 to 6.34 (95% CI:6.15-6.47) in 2011, for both in situ (2004:0.73;2011:1.24) and invasive cancers (2004:4.42;2011:5.07), whereas the ICR remained stable (2004: 2.16 (95% CI2.06-2.25);2011: 2.13 (95% CI:2.04-2.22)). The RR changed significantly from 14.0 to 21.4. Programme sensitivity significantly increased, mainly between ages 49-59, from 70.0% (95% CI:68.9-71.2) to 74.4% (95% CI:73.5-75.4) whereas specificity slightly declined (2004:99.1% (95% CI:99.09-99.13);2011:98.5% (95% CI:98.45-98.50)). The overall DR was significantly higher for DM than for SFM (6.24;5.36) as was programme sensitivity (73.6%;70.1%), the ICR was similar (2.19;2.20) and specificity was significantly lower for DM (98.5%;98.9%). CONCLUSIONS: During the transition from SFM to DM, there was a significant rise in DR and a stable ICR, leading to increased programme sensitivity. Although the recall rate increased, programme specificity remained high compared to other countries. These findings indicate that the performance of DM in a nationwide screening programme is not inferior to, and may be even better, than that of SFM.

Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSPC and PLCO Trials.

BACKGROUND: The ERSPC (European Randomized Study of Screening for Prostate Cancer) found that screening reduced prostate cancer mortality, but the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) found no reduction. OBJECTIVE: To evaluate whether effects of screening on prostate cancer mortality relative to no screening differed between the ERSPC and PLCO. DESIGN: Cox regression of prostate cancer death in each trial group, adjusted for age and trial. Extended analyses accounted for increased incidence due to screening and diagnostic work-up in each group via mean lead times (MLTs), which were estimated empirically and using analytic or microsimulation models. SETTING: Randomized controlled trials in Europe and the United States. PARTICIPANTS: Men aged 55 to 69 (ERSPC) or 55 to 74 (PLCO) years at randomization. INTERVENTION: Prostate cancer screening. MEASUREMENTS: Prostate cancer incidence and survival from randomization; prostate cancer incidence in the United States before screening began. RESULTS: Estimated MLTs were similar in the ERSPC and PLCO intervention groups but were longer in the PLCO control group than the ERSPC control group. Extended analyses found no evidence that effects of screening differed between trials (P = 0.37 to 0.47 [range across MLT estimation approaches]) but strong evidence that benefit increased with MLT (P = 0.0027 to 0.0032). Screening was estimated to confer a 7% to 9% reduction in the risk for prostate cancer death per year of MLT. This translated into estimates of 25% to 31% and 27% to 32% lower risk for prostate cancer death with screening as performed in the ERSPC and PLCO intervention groups, respectively, compared with no screening. LIMITATION: The MLT is a simple metric of screening and diagnostic work-up. CONCLUSION: After differences in implementation and settings are accounted for, the ERSPC and PLCO provide compatible evidence that screening reduces prostate cancer mortality. PRIMARY FUNDING SOURCE: National Cancer Institute.

The effect of population-based mammography screening in Dutch municipalities on breast cancer mortality: 20 years of follow-up.

Long-term follow-up data on the effects of screening are scarce, and debate exists on the relative contribution of screening versus treatment to breast cancer mortality reduction. Our aim was therefore to assess the long-term effect of screening by age and time of implementation. We obtained data on 69,630 breast cancer deaths between 1980 and 2010 by municipality (N = 431) and age of death (40-79) in the Netherlands. Breast cancer mortality trends were analyzed by defining the municipality-specific calendar year of introduction of screening as Year 0. Additionally, log-linear Poisson regression was used to estimate the turning point in the trend after Year 0, per municipality, and the annual percentage change (APC) before and after this point. Twenty years after introduction of screening breast cancer mortality was reduced by 30% in women aged 55-74 and by 34% in women aged 75-79, compared to Year 0. A similar and significant decrease was present in municipalities that started early (1987-1992) and late (1995-1997) with screening, despite the difference in availability of effective adjuvant treatment. In the age groups 55-74 and 75-79, the turning point in the trend in breast cancer mortality was estimated in Years 2 and 6 after the introduction of screening, respectively, after which mortality decreased significantly by 1.9% and 2.6% annually. These findings show that the implementation of mammography screening in Dutch municipalities is associated with a significant decline in breast cancer mortality in women aged 55-79, irrespective of time of implementation.

When should active surveillance for prostate cancer stop if no progression is detected?

BACKGROUND: A significant proportion of screen-detected men with prostate cancer may be overdiagnosed. Active Surveillance (AS) has emerged as a way to mitigate this problem, by delaying treatment of men, who are at low-risk until this becomes necessary. However, it is not known after how much time or biopsy rounds should patients stop AS and transition to conservative management (CM), if no progression is detected. METHODS: We used a microsimulation model with natural history of prostate cancer based on ERSPC and SEER data. We modeled referral to treatment while in AS, based on Johns Hopkins treatment-free survival data. We projected lifetime costs and effects of AS (and radical treatment, if progression is detected) under different biopsy follow-up schedules compared to CM, where radical treatment only occurs when men would be clinically diagnosed in absence of screening. RESULTS: For men with low-risk disease in younger age groups (55-65), AS is cost-effective for up to 7 yearly biopsy rounds. For men older than 65, even one biopsy round results in quality adjusted life years (QALYs) lost, though it may result in QALYs gained for men without previous screening. For men with intermediate-risk disease AS is cost-effective even for men in 65-75 age group. CONCLUSIONS: The benefit of AS when compared to CM is strongly dependent on life expectancy and disease risk. Clinicians should take this into account when selecting men to AS, deciding on biopsy frequency and when to stop AS surveillance rounds and transition to CM.

Is prostate cancer different in black men? Answers from 3 natural history models.

BACKGROUND: Black men in the United States have substantially higher prostate cancer incidence rates than the general population. The extent to which this incidence disparity is because prostate cancer is more prevalent, more aggressive, and/or more frequently diagnosed in black men is unknown. METHODS: The authors estimated 3 independently developed models of prostate cancer natural history in black men and in the general population using an updated reconstruction of prostate-specific antigen screening, based on the National Health Interview Survey in 2005 and on prostate cancer incidence data from the Surveillance, Epidemiology, and End Results program during 1975 through 2000. By using the estimated models, the natural history of prostate cancer was compared between black men and the general population. RESULTS: The models projected that from 30% to 43% (range across models) of black men develop preclinical prostate cancer by age 85 years, a risk that is (relatively) 28% to 56% higher than that in the general population. Among men who had preclinical disease onset, black men had a similar risk of diagnosis (range, 35%-49%) compared with the general population (32%-44%), but their risk of progression to metastatic disease by the time of diagnosis was from 44% to 75% higher than that in the general population. CONCLUSIONS: Prostate cancer incidence patterns implicate higher incidence of preclinical disease and higher risk of metastatic progression among black men. The findings suggest screening black men earlier than white men and support further research into the benefit-harm tradeoffs of more aggressive screening policies for black men. Cancer 2017;123:2312-2319. © 2017 American Cancer Society.

Estimating the risks and benefits of active surveillance protocols for prostate cancer: a microsimulation study.

OBJECTIVE: To estimate the increase in prostate cancer mortality (PCM) and the reduction in overtreatment resulting from different active surveillance (AS) protocols, compared with treating men immediately. PATIENTS AND METHODS: We used a microsimulation model (MISCAN-Prostate), with the natural history of prostate cancer based on European Randomized Study of Screening for Prostate Cancer data. We estimated the probabilities of referral to radical treatment while on AS, depending on disease stage, using data from the Johns Hopkins AS cohort. We sampled 10 million men, representative of the US population, and projected the effects of applying AS protocols that differed by time between biopsies and compared these with the effects of treating men immediately. RESULTS: We found that AS with yearly follow-up biopsies for men with low-risk prostate cancer (≤ T2a stage and Gleason 6) increases the probability of PCM to 2.6% (1% increase) and reduces overtreatment from 2.5 to 2.1% (18.4% reduction). With biopsies every 3 years after the first year, PCM increases by 2.3% and overtreatment reduces from 2.5 to 1.9% (30.3% reduction). The inclusion of men in the intermediate-risk group (> T2a stage or Gleason 3+4) in AS protocols increases PCM by 2.7% and reduces overtreatment from 2.5 to 2.0% (23.1% reduction). These results may not apply to African-American men. CONCLUSIONS: Offering AS to men with low-risk prostate cancer is relatively safe. Increasing the biopsy interval from yearly to up to every 3 years after the first year will significantly reduce overtreatment among men in the low-risk group, with limited PCM risk.