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

To be screened or not to be screened Modeling the consequences of PSA screening for the individual

Background:Screening with prostate-specific antigen (PSA) can reduce prostate cancer mortality, but may advance diagnosis and treatment in time and lead to overdetection and overtreatment. We estimated benefits and adverse effects of PSA screening for individuals who are deciding whether or not to be screened.Methods:Using a microsimulation model, we estimated lifetime probabilities of prostate cancer diagnosis and death, overall life expectancy and expected time to diagnosis, both with and without screening. We calculated anticipated loss in quality of life due to prostate cancer diagnosis and treatment that would be acceptable to decide in favour of screening.Results:Men who were screened had a gain in life expectancy of 0.08 years but their expected time to diagnosis decreased by 1.53 life-years. Of the screened men, 0.99% gained on average 8.08 life-years and for 17.43% expected time to diagnosis decreased by 8.78 life-years. These figures imply that the anticipated loss in quality of life owing to diagnosis and treatment should not exceed 4.8%, for screening to have a positive effect on quality-adjusted life expectancy.Conclusion:The decision to be screened should depend on personal preferences. The negative impact of screening might be reduced by screening men who are more willing to accept the side effects from treatment

Prognostic value of heart valve calcifications for cardiovascular events in a lung cancer screening population

To assess the prognostic value of aortic valve and mitral valve/annulus calcifications for cardiovascular events in heavily smoking men without a history of cardiovascular disease. Heavily smoking men without a cardiovascular disease history who underwent non-contrast-enhanced low-radiation-dose chest CT for lung cancer screening were included. Non-imaging predictors (age, smoking status and pack-years) were collected and imaging-predictors (calcium volume of the coronary arteries, aorta, aortic valve and mitral valve/annulus) were obtained. The outcome was the occurrence of cardiovascular events. Multivariable Cox proportional-hazards regression was used to calculate hazard-ratios (HRs) with 95 % confidence interval (CI). Subsequently, concordance-statistics were calculated. In total 3111 individuals were included, of whom 186 (6.0 %) developed a cardiovascular event during a follow-up of 2.9 (Q1–Q3, 2.7–3.3) years. If aortic (n = 657) or mitral (n = 85) annulus/valve calcifications were present, cardiovascular event incidence increased to 9.0 % (n = 59) or 12.9 % (n = 11), respectively. HRs of aortic and mitral valve/annulus calcium volume for cardiovascular events were 1.46 (95 % CI, 1.09–1.84) and 2.74 (95 % CI, 0.92–4.56) per 500 mm3. The c-statistic of a basic model including age, pack-years, current smoking status, coronary and aorta calcium volume was 0.68 (95 % CI, 0.63–0.72), which did not change after adding heart valve calcium volume. Aortic valve calcifications are predictors of future cardiovascular events. However, there was no added prognostic value beyond age, number of pack-years, current smoking status, coronary and aorta calcium volume for short term cardiovascular events

The second round of the Dutch colorectal cancer screening program: Impact of an increased fecal immunochemical test cut-off level on yield of screening

The Dutch colorectal cancer (CRC) screening program started in 2014, inviting the target population biennially to perform a fecal immunochemical test (FIT). We obtained prospectively collected data from the national screening information-system to present the results of the second round (2016) and evaluate the impact of increasing the FIT cut-off halfway through the first round from 15 to 47 μg Hb/g feces on outcomes in the second round. Second round screening was done with a 47 μg Hb/g feces FIT cut-off. Participants were classified based on first round participation status as either FIT (15,47) or FIT (47,47) participants, and previous nonparticipants. In total, 348,891 (75.9%) out of 459,740 invitees participated in the second round. Participation rates were 93.4% among previous participants and 21.0% among previous non-participants. FIT(47,47) participants had a significantly higher detection rate of AN (15.3 vs. 10.4 per 1,000 participants) compared to FIT(15,47) participants in the second round, while their cumulative detection rate of AN over two rounds was significantly lower (45.6 vs. 52.6 per 1,000 participants). Our results showed that participation in the Dutch CRC screening program was consistently high and that second round detection rates depended on the first round FIT cut-off. The cumulative detection over two rounds was higher among FIT(15,47) participants. These findings suggest that a substantial part of, but not all the missed findings in the first round due to the increased FIT cut-off were detected in the subsequent round

A Comparative Modeling Analysis of Risk-Based Lung Cancer Screening Strategies

Background: Risk-prediction models have been proposed to select individuals for lung cancer screening. However, their longterm effects are uncertain. This study evaluates long-term benefits and harms of risk-based screening compared with current United States Preventive Services Task Force (USPSTF) recommendations. Methods: Four independent natural history models were used to perform a comparative modeling study evaluating longterm benefits and harms of selecting individuals for lung cancer screening through risk-prediction models. In total, 363 riskbased screening strategies varying by screening starting and stopping age, risk-prediction model used for eligibility (Bach, PLCOm2012, or Lung Cancer Death Risk Assessment Tool [LCDRAT]), and risk threshold were evaluated for a 1950 US birth cohort. Among the evaluated outcomes were percentage of individuals ever screened, screens required, lung cancer deaths averted, life-years gained, and overdiagnosis. Results: Risk-based screening strategies requiring sim

Key indicators of organized cancer screening programs: Results from a Delphi study

Objective To maximize benefits and reduce potential harms of organized cancer screening programs in Europe, monitoring, quality assurance, and evaluation of long-term impact are required. We aimed to identify the most important indicators to be collected and reported. The study was designed to establish a consensus within a European-level working group and suggest a manageable list of key indicators. Methods We conducted a Delphi study among policymakers, researchers, and program coordinators who were experts in breast, cervical, or colorectal cancer screening. Study participants evaluated the importance of screening indicators on a 5-point Likert scale. Results The top 10 indicators by study participants were interval cancer rate, detection rate, screening attendance, screening coverage, cancer incidence

Personalizing Breast Cancer Screening Based on Polygenic Risk and Family History

_Background:_ We assessed the clinical utility of a first-degree breast cancer family history and polygenic risk score (PRS) to inform screening decisions among women aged 30-50 years. _Methods:_ Two established breast cancer models evaluated digital mammography screening strategies in the 1985 US birth cohort by risk groups defined by family history and PRS based on 313 single nucleotide polymorphisms. Strategies varied in initiation age and interval. The benefits and harms were compared with those seen with 3 established screening guidelines. _Results:_ Women with a breast cancer family history who initiated biennial screening at age 40 years had a 36% increase in life-years gained and 20% more breast cancer deaths averted, but 21% more overdiagnoses and 63% more false positives. Screening tailored to PRS vs biennial screening from50 to 74 years had smaller positive effects on life-years gained and breast cancer deaths averted but also smaller increases in overdiagnoses and false positives. Combined use of family history and PRS vs biennial screening from 50 to 74 years had the greatest increase in life-years gained and breast cancer deaths averted. _Conclusions:_ Our results suggest that breast cancer family history and PRS could guide screening decisions before age 50 years among women at increased risk for breast cancer but expected increases in overdiagnoses and false positives should be expected

Impact of cause of death adjudication on the results of the European prostate cancer screening trial

Background:The European Randomised Study of Prostate Cancer Screening has shown a 21% relative reduction in prostate cancer mortality at 13 years. The causes of death can be misattributed, particularly in elderly men with multiple comorbidities, and therefore accurate assessment of the underlying cause of death is crucial for valid results. To address potential unreliability of end-point assessment, and its possible impact on mortality results, we analysed the study outcome adjudication data in six countries.Methods:Latent class statistical models were formulated to compare the accuracy of individual adjudicators, and to assess whether accuracy differed between the trial arms. We used the model to assess whether correcting for adjudication inaccuracies might modify the study results.Results:There was some heterogeneity in adjudication accuracy of causes of death, but no consistent differential accuracy by trial arm. Correcting the estimated screening effect for misclassification did not alter the estimated mortality effect of screening.Conclusions:Our findings were consistent with earlier reports on the European screening trial. Observer variation, while demonstrably present, is unlikely to have materially biased the main study results. A bias in assigning causes of death that might have explained the mortality reduction by screening can be effectively ruled out

Comparing benefits from many possible computed tomography lung cancer screening programs: Extrapolating from the National Lung Screening Trial using comparative modeling

Background: The National Lung Screening Trial (NLST) demonstrated that in current and former smokers aged 55 to 74 years, with at least 30 pack-years of cigarette smoking history and who had quit smoking no more than 15 years ago, 3 annual computed tomography (CT) screens reduced lung cancer-specific mortality by 20% relative to 3 annual chest X-ray screens. We compared the benefits achievable with 576 lung cancer screening programs that varied CT screen number and frequency, ages of screening, and eligibility based on smoking. Methods and Findings: We used five independent microsimulation models with lung cancer natural history parameters previously calibrated to the NLST to simulate life histories of the US cohort born in 1950 under all 576 programs. 'Efficient' (within model) programs prevented the greatest number of lung cancer deaths, compared to no screening, for a given number of CT screens. Among 120 'consensus efficient' (identified as efficient across models) programs, the average starting age was 55 years, the stopping age was 80 or 85 years, the average minimum pack-years was 27, and the maximum years since quitting was 20. Among consensus efficient programs, 11% to 40% of the cohort was screened, and 153 to 846 lung cancer deaths were averted per 100,000 people. In all models, annual screening based on age and smoking eligibility in NLST was not efficient; continuing screening to age 80 or 85 years was more efficient. Conclusions: Consensus results from five models identified a set of efficient screening programs that include annual CT lung cancer screening using criteria like NLST eligibility but extended to older ages. Guidelines for screening should also consider harms of screening and individual patient characteristics