The role of modelling in the policy decision making process for cancer screening : Example of prostate specific antigen screening

Funding Information: This publication was made possible by Grant Number U01 CA199338 from the National Cancer Institute as part of the Cancer Intervention and Surveillance Modeling Network, which supported the underlying development of the simulation model utilised. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.Peer reviewe

Exploring the relation of active surveillance schedules and prostate cancer mortality

Background: Active surveillance (AS), where treatment is deferred until cancer progression is detected by a biopsy, is acknowledged as a way to reduce overtreatment in prostate cancer. However, a consensus on the frequency of taking biopsies while in AS is lacking. In former studies to optimize biopsy schedules, the delay in progression detection was taken as an evaluation indicator and believed to be associated with the long-term outcome, prostate cancer mortality. Nevertheless, this relation was never investigated in empirical data. Here, we use simulated data from a microsimulation model to fill this knowledge gap. Methods: In this study, the established MIcrosimulation SCreening Analysis model was extended with functionality to simulate the AS procedures. The biopsy sensitivity in the model was calibrated on the Canary Prostate Cancer Active Surveillance Study (PASS) data, and four (tri-yearly, bi-yearly, PASS, and yearly) AS programs were simulated. The relation between detection delay and prostate cancer mortality was investigated by Cox models. Results: The biopsy sensitivity of progression detection was found to be 50%. The Cox models show a positive relation between a longer detection delay and a higher risk of prostate cancer death. A 2-year delay resulted in a prostate cancer death risk of 2.46%–2.69% 5 years after progression detection and a 10-year risk of 5.75%–5.91%. A 4-year delay led to an approximately 8% greater 5-year risk and an approximately 25% greater 10-year risk. Conclusion: The detection delay is confirmed as a surrogate for prostate cancer mortality. A cut-off for a “safe” detection delay could not be identified.</p

The role of modelling in the policy decision making process for cancer screening: example of prostate specific antigen screening

Although randomised controlled trials are the preferred basis for policy decisions on cancer screening, it remains diffcult to assess all downstream effects of screening, particularly when screening options other than those in the specifc trial design are being considered. Simulation models of the natural history of disease can play a role in quantifying harms and benefts of cancer screening scenarios. Recently, the US Preventive Services Task Force issued a C-recommendation on screening for prostate cancer for men aged 55–69 years, implying at le

Screening for cancers with a good prognosis:The case of testicular germ cell cancer

Background: To determine, using testicular germ cell cancer screening as an example, whether screening can also be effective for cancers with a good prognosis. Methods: Based on the Dutch incidence, stage distribution, and survival and mortality data of testicular germ cell cancer, we developed a microsimulation model. This model simulates screening scenarios varying in screening age, interval, self-examination or screening by the general practitioner (GP), and screening of a defined high-risk group (cryptorchidism). For each scenario, the number of clinically and screen-detected cancers by stage, referrals, testicular germ cell cancer deaths, and life-years gained were projected. Results: Annual self-examination from age 20 to 30 years resulted in 767 cancers detected per 100,000 men followed over life-time, of which 123 (16%) by screening. In this scenario, 19.2 men died from the disease, 4.7 (20%) less than without screening, and 230 life-years were gained. Around 14,000 visits to the GP and 2080 visits to an urologist were required. This scenario resulted in the most favorable ratio between extra visits to the GP or urologist and deaths prevented (1418 and 116 respectively). Monthly screening, or screening until age 40 resulted in less favorable ratios. Self-examination by only the high-risk population prevented 1.0 death per 100,00 men in the general population. In all scenarios, 46–50 life-years were gained for each testicular germ cell cancer death prevented. Conclusion: Despite the good prognosis, self-examination at young ages for testicular germ cell cancer could be considered

The comparative effectiveness of mpMRI and MRI-guided biopsy vs regular biopsy in a population-based PSA testing: a modeling study

The benefit of prostate cancer screening is counterbalanced by the risk of overdiagnosis and overtreatment. The use of a multi-parametric magnetic resonance imaging (mpMRI) test after a positive prostate-specific antigen (PSA) test followed by magnetic resona

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

Assessment of harms, benefits, and cost-effectiveness of prostate cancer screening: A micro-simulation study of 230 scenarios

Background: Prostate cancer screening incurs a high risk of overdiagnosis and overtreatment. An organized and age-targeted screening strategy may reduce the associated harms while retaining or enhancing the benefits. Methods: Using a micro-simulation analysis (MISCAN) model, we assessed the harms, benefits, and cost-effectiveness of 230 prostate-specific antigen (PSA) screening strategies in a Dutch population. Screening strategies were varied by screening start age (50, 51, 52, 53, 54, and 55), stop age (51-69), and intervals (1, 2, 3, 4, 8, and single test). Costs and effects of each screening strategy were compared with a no-screening scenario. Results: The most optimum strategy would be screening with 3-year intervals at ages 55–64 resulting in an incremental cost-effectiveness ratio (ICER) of €19 733 per QALY. This strategy predicted a 27

Breast Cancer Screening in Georgia:Choosing the Most Optimal and Cost-Effective Strategy

Objectives: To define the optimal and cost-effective breast cancer screening strategy for Georgia. Methods: We used the Microsimulation Screening Analysis-Breast (MISCAN-Breast) model that has been adapted to the Georgian situation to evaluate 736 mammography screening strategies varied by interval (biennial and triennial), starting ages (40-60 years), stopping ages (64-84 years), and screening modality (with and without clinical breast examination [CBE]). Quality-adjusted life-years (QALYs) and additional cost (healthcare perspective) compared with no screening per 1000 women were calculated with 3% discount. Major uncertainties (eg, costs) are addressed as sensitivity analyses. Results: Strategies using a combination of mammography and CBE yielded in substantially higher costs with minimal differences in outcomes compared with mammography-only strategies. The current screening strategy, biennial mammography screening from the age of 40 until 70 years with CBE, is close to the frontier line but requires high additional cost given the QALY gains (€16 218/QALY), well above the willingness-to-pay threshold of €12 720. The optimal strategy in Georgia would be triennial mammography-only screening from age 45 to 66 years with an incremental cost-effectiveness ratio of €12 507. Conclusions: Biennial screening strategies are resource-intensive strategies and may not be feasible for Georgia. By switching to triennial mammography-only strategy from the age of 45 until 66 years, it is possible to offer screening to more eligible women while still gaining substantial screening benefits. This is to address capacity issues which is a common barrier for many Eastern European countries.</p