Quantifying and monitoring overdiagnosis in cancer screening: a systematic review of methods.
ABSTRACT: To determine the optimal method for quantifying and monitoring overdiagnosis in cancer screening over time.Systematic review of primary research studies of any design that quantified overdiagnosis from screening for nine types of cancer. We used explicit criteria to critically appraise individual studies and assess strength of the body of evidence for each study design (double blinded review), and assessed the potential for each study design to accurately quantify and monitor overdiagnosis over time.PubMed and Embase up to 28 February 2014; hand searching of systematic reviews.English language studies of any design that quantified overdiagnosis for any of nine common cancers (prostate, breast, lung, colorectal, melanoma, bladder, renal, thyroid, and uterine); excluded case series, case reports, and reviews that only reported results of other studies.52 studies met the inclusion criteria. We grouped studies into four methodological categories: (1) follow-up of a well designed randomized controlled trial (n=3), which has low risk of bias but may not be generalizable and is not suitable for monitoring; (2) pathological or imaging studies (n=8), drawing conclusions about overdiagnosis by examining biological characteristics of cancers, a simple design limited by the uncertain assumption that the measured characteristics are highly correlated with disease progression; (3) modeling studies (n=21), which can be done in a shorter time frame but require complex mathematical equations simulating the natural course of screen detected cancer, the fundamental unknown question; and (4) ecological and cohort studies (n=20), which are suitable for monitoring over time but are limited by a lack of agreed standards, by variable data quality, by inadequate follow-up time, and by the potential for population level confounders. Some ecological and cohort studies, however, have addressed these potential weaknesses in reasonable ways.Well conducted ecological and cohort studies in multiple settings are the most appropriate approach for quantifying and monitoring overdiagnosis in cancer screening programs. To support this work, we need internationally agreed standards for ecological and cohort studies and a multinational team of unbiased researchers to perform ongoing analysis.
Project description:Overdiagnosis of thyroid cancer was propounded regarding the rapidly increasing incidence in South Korea. Overdiagnosis is defined as 'the detection of cancers that would never have been found were it not for the screening test', and may be an extreme form of lead bias due to indolent cancers, as is inevitable when conducting a cancer screening programme. Because it is solely an epidemiological concept, it can be estimated indirectly by phenomena such as a lack of compensatory drop in post-screening periods, or discrepancies between incidence and mortality. The erstwhile trials for quantifying the overdiagnosis in screening mammography were reviewed in order to secure the data needed to establish its prevalence in South Korea.
Project description:The U.S. Preventive Services Task Force recently concluded that the harms of existing prostate-specific antigen (PSA) screening strategies outweigh the benefits.To evaluate comparative effectiveness of alternative PSA screening strategies.Microsimulation model of prostate cancer incidence and mortality quantifying harms and lives saved for alternative PSA screening strategies.National and trial data on PSA growth, screening and biopsy patterns, incidence, treatment distributions, treatment efficacy, and mortality.A contemporary cohort of U.S. men.Lifetime.Societal.35 screening strategies that vary by start and stop ages, screening intervals, and thresholds for biopsy referral.PSA tests, false-positive test results, cancer detected, overdiagnoses, prostate cancer deaths, lives saved, and months of life saved.Without screening, the risk for prostate cancer death is 2.86%. A reference strategy that screens men aged 50 to 74 years annually with a PSA threshold for biopsy referral of 4 µg/L reduces the risk for prostate cancer death to 2.15%, with risk for overdiagnosis of 3.3%. A strategy that uses higher PSA thresholds for biopsy referral in older men achieves a similar risk for prostate cancer death (2.23%) but reduces the risk for overdiagnosis to 2.3%. A strategy that screens biennially with longer screening intervals for men with low PSA levels achieves similar risks for prostate cancer death (2.27%) and overdiagnosis (2.4%), but reduces total tests by 59% and false-positive results by 50%.Varying incidence inputs or reducing the survival improvement due to screening did not change conclusions.The model is a simplification of the natural history of prostate cancer, and improvement in survival due to screening is uncertain.Compared with standard screening, PSA screening strategies that use higher thresholds for biopsy referral for older men and that screen men with low PSA levels less frequently can reduce harms while preserving lives.National Cancer Institute and Centers for Disease Control and Prevention.
Project description:Systematic reviews for the US Preventive Services Task Force have found less high-quality evidence on psychological than physical harms of screening. To understand the extent of evidence on psychological harms, we developed an evidence map that quantifies the distribution of evidence on psychological harms for five adult screening services. We also note gaps in the literature and make recommendations for future research.We systematically searched PubMed, PsycInfo, and CINAHL from 2002 to 2012 for studies of any research design that assessed the burden or frequency of psychological harm associated with screening for: prostate and lung cancers, osteoporosis, abdominal aortic aneurysm (AAA) and carotid artery stenosis (CAS). We also searched for studies that estimated rates of overdiagnosis (a marker for unnecessary labeling). We included studies published in English and used dual independent review to determine study inclusion and to abstract information on design, types of measures, and outcomes assessed.Sixty-eight studies assessing psychological harms met our criteria; 62 % concerned prostate cancer and 16 % concerned lung cancer. Evidence was scant for the other three screening services. Overall, only about one-third of the studies used both longitudinal designs and condition-specific measures (ranging from 0 % for AAA and CAS to 78 % for lung cancer), which can provide the best evidence on harms. An additional 20 studies that met our criteria estimated rates of overdiagnosis in lung or prostate cancer. No studies estimated overdiagnosis for the non-cancer screening services.Evidence on psychological harms varied markedly across screening services in number and potential usefulness. We found important evidence gaps for all five screening services. The evidence that we have on psychological harms is inadequate in number of studies and in research design and measures. Future research should focus more clearly on the evidence that we need for decision making about screening.
Project description:OBJECTIVE: To elicit women's responses to information about the nature and extent of overdiagnosis in mammography screening (detecting disease that would not present clinically during the woman's lifetime) and explore how awareness of overdiagnosis might influence attitudes and intentions about screening. DESIGN: Qualitative study using focus groups that included a presentation explaining overdiagnosis, incorporating different published estimates of its rate (1-10%, 30%, 50%) and information on the mortality benefit of screening, with guided group discussions SETTING: Sydney, Australia PARTICIPANTS: Fifty women aged 40-79 years with no personal history of breast cancer and with varying levels of education and participation in screening. RESULTS: Prior awareness of breast cancer overdiagnosis was minimal. Women generally reacted with surprise, but most came to understand the issue. Responses to overdiagnosis and the different estimates of its magnitude were diverse. The highest estimate (50%) made some women perceive a need for more careful personal decision making about screening. In contrast, the lower and intermediate estimates (1-10% and 30%) had limited impact on attitudes and intentions, with many women remaining committed to screening. For some women, the information raised concerns, not about whether to screen but whether to treat a screen detected cancer or consider alternative approaches (such as watchful waiting). Information preferences varied: many women considered it important to take overdiagnosis into account and make informed choices about whether to have screening, but many wanted to be encouraged to be screened. CONCLUSIONS: Women from a range of socioeconomic backgrounds could comprehend the issue of overdiagnosis in mammography screening, and they generally valued information about it. Effects on screening intentions may depend heavily on the rate of overdiagnosis. Overdiagnosis will be new and counterintuitive for many people and may influence screening and treatment decisions in unintended ways, underscoring the need for careful communication.
Project description:Despite evidence about the "modern epidemic" of overdiagnosis, and expanding disease definitions that medicalize more people, data are lacking on public views about these issues. Our objective was to measure public perceptions about overdiagnosis and views about financial ties of panels setting disease definitions.We conducted a 15 minute Computer Assisted Telephone Interview with a randomly selected community sample of 500 Australians in January 2014. We iteratively developed and piloted a questionnaire, with a convenience sample (n=20), then with participants recruited by a research company (n=20). Questions included whether respondents had been informed about overdiagnosis; opinions on informing people; and views about financial ties among panels writing disease definitions.Our sample was generally representative, but included a higher proportion of females and seniors, typical of similar surveys. American Association for Public Opinion Research response rate was 20% and cooperation rate was 44%. Only 10% (95% CI 8%-13%) of people reported ever being told about overdiagnosis by a doctor. 18% (95% CI 11%-28%) of men who reported having prostate cancer screening, and 10% (95% CI 6%-15%) of women who reported having mammography said they were told about overdiagnosis. 93% (95% CI 90%-95%) agreed along with screening benefits, people should be informed about overdiagnosis. On panels setting disease definitions, 78% (95% CI 74%-82%) felt ties to pharmaceutical companies inappropriate, and 91% (95% CI 82%-100%) believed panels should have a minority or no members with ties. Limitations included questionnaire novelty and complexity.A small minority of Australians surveyed, including those reporting being screened for prostate or breast cancer, reported being informed of overdiagnosis; most believed people should be informed; and a majority felt it inappropriate that doctors with ties to pharmaceutical companies write disease definitions. Results suggest strategies to better inform people about overdiagnosis, and review disease definition processes, have significant public sympathy.
Project description:The U.S. Preventive Services Task Force (USPSTF) recently updated their national lung screening guidelines and recommended low-dose computed tomography (LDCT) for lung cancer (LC) screening through age 80. However, the risk of overdiagnosis among older populations is a concern. Using four comparative models from the Cancer Intervention and Surveillance Modeling Network, we evaluate the overdiagnosis of the screening program recommended by USPSTF in the U.S. 1950 birth cohort. We estimate the number of LC deaths averted by screening (D) per overdiagnosed case (O), yielding the ratio D/O, to quantify the trade-off between the harms and benefits of LDCT. We analyze 576 hypothetical screening strategies that vary by age, smoking, and screening frequency and evaluate efficient screening strategies that maximize the D/O ratio and other metrics including D and life-years gained (LYG) per overdiagnosed case. The estimated D/O ratio for the USPSTF screening program is 2.85 (model range: 1.5-4.5) in the 1950 birth cohort, implying LDCT can prevent ?3 LC deaths per overdiagnosed case. This D/O ratio increases by 22% when the program stops screening at an earlier age 75 instead of 80. Efficiency frontier analysis shows that while the most efficient screening strategies that maximize the mortality reduction (D) irrespective of overdiagnosis screen through age 80, screening strategies that stop at age 75 versus 80 produce greater efficiency in increasing life-years gained per overdiagnosed case. Given the risk of overdiagnosis with LC screening, the stopping age of screening merits further consideration when balancing benefits and harms.
Project description:OBJECTIVE: To use data from two longstanding, population based screening programmes to study overdiagnosis in screening mammography. DESIGN: Population based cohort study. SETTING: Copenhagen municipality (from 1991) and Funen County (from 1993), Denmark. PARTICIPANTS: 57,763 women targeted by organised screening, aged 56-69 when the screening programmes started, and followed up to 2009. MAIN OUTCOME MEASURES: Overdiagnosis of breast cancer in women targeted by screening, assessed by relative risks compared with historical control groups from screening regions, national control groups from non-screening regions, and historical national control groups. RESULTS: In total, 3279 invasive breast carcinomas and ductal carcinomas in situ occurred. The start of screening led to prevalence peaks in breast cancer incidence: relative risk 2.06 (95% confidence interval 1.64 to 2.59) for Copenhagen and 1.84 (1.46 to 2.32) for Funen. During subsequent screening rounds, relative risks were slightly above unity: 1.04 (0.85 to 1.27) for Copenhagen and 1.14 (0.98 to 1.32) for Funen. A compensatory dip was seen after the end of invitation to screening: relative risk 0.80 (0.65 to 0.98) for Copenhagen and 0.67 (0.55 to 0.81) for Funen during the first four years. The relative risk of breast cancer accumulated over the entire follow-up period was 1.06 (0.90 to 1.25) for Copenhagen and 1.01 (0.93 to 1.10) for Funen. Relative risks for participants corrected for selection bias were estimated to be 1.08 for Copenhagen and 1.02 for Funen; for participants followed for at least eight years after the end of screening, they were 1.05 and 1.01. A pooled estimate gave 1.040 (0.99 to 1.09) for all targeted women and 1.023 (0.97 to 1.08) for targeted women followed for at least eight years after the end of screening. CONCLUSIONS: On the basis of combined data from the two screening programmes, this study indicated that overdiagnosis most likely amounted to 2.3% (95% confidence interval -3% to 8%) in targeted women. Among participants, it was most likely 1-5%. At least eight years after the end of screening were needed to compensate for the excess incidence during screening.
Project description:Screening for lung cancer has the potential to reduce mortality, but in addition to detecting aggressive tumors, screening will also detect indolent tumors that otherwise may not cause clinical symptoms. These overdiagnosis cases represent an important potential harm of screening because they incur additional cost, anxiety, and morbidity associated with cancer treatment.To estimate overdiagnosis in the National Lung Screening Trial (NLST).We used data from the NLST, a randomized trial comparing screening using low-dose computed tomography (LDCT) vs chest radiography (CXR) among 53?452 persons at high risk for lung cancer observed for 6.4 years, to estimate the excess number of lung cancers in the LDCT arm of the NLST compared with the CXR arm.We calculated 2 measures of overdiagnosis: the probability that a lung cancer detected by screening with LDCT is an overdiagnosis (PS), defined as the excess lung cancers detected by LDCT divided by all lung cancers detected by screening in the LDCT arm; and the number of cases that were considered overdiagnosis relative to the number of persons needed to screen to prevent 1 death from lung cancer.During follow-up, 1089 lung cancers were reported in the LDCT arm and 969 in the CXR arm of the NLST. The probability is 18.5% (95% CI, 5.4%-30.6%) that any lung cancer detected by screening with LDCT was an overdiagnosis, 22.5% (95% CI, 9.7%-34.3%) that a non-small cell lung cancer detected by LDCT was an overdiagnosis, and 78.9% (95% CI, 62.2%-93.5%) that a bronchioalveolar lung cancer detected by LDCT was an overdiagnosis. The number of cases of overdiagnosis found among the 320 participants who would need to be screened in the NLST to prevent 1 death from lung cancer was 1.38.More than 18% of all lung cancers detected by LDCT in the NLST seem to be indolent, and overdiagnosis should be considered when describing the risks of LDCT screening for lung cancer.
Project description:OBJECTIVES:To quantify the risk of overdiagnosis associated with prostate cancer screening in Australia using a novel lifetime risk approach. DESIGN:Modelling and validation of the lifetime risk method using publicly available population data. SETTING:Opportunistic screening for prostate cancer in the Australian population. PARTICIPANTS:Australian male population (1982-2012). INTERVENTIONS:Prostate-specific antigen testing for prostate cancer screening. PRIMARY AND SECONDARY OUTCOME MEASURES:Primary: lifetime risk of overdiagnosis in 2012 (excess lifetime cancer risk adjusted for changing competing mortality); Secondary: lifetime risk of prostate cancer diagnosis (unadjusted and adjusted for competing mortality); Excess lifetime risk of prostate cancer diagnosis (for all years subsequent to 1982). RESULTS:The lifetime risk of being diagnosed with prostate cancer increased from 6.1% in 1982 (1 in 17) to 19.6% in 2012 (1 in 5). Using 2012 competing mortality rates, the lifetime risk in 1982 was 11.5% (95% CI 11.0% to 12.0%). The excess lifetime risk of prostate cancer in 2012 (adjusted for changing competing mortality) was 8.2% (95% CI 7.6% to 8.7%) (1 in 13). This corresponds to 41% of prostate cancers being overdiagnosed. CONCLUSIONS:Our estimated rate of overdiagnosis is in agreement with estimates using other methods. This method may be used without the need to adjust for lead times. If annual (cross-sectional) data are used, then it may give valid estimates of overdiagnosis once screening has been established long enough for the benefits from the early detection of non-overdiagnosed cancer at a younger age to be realised in older age groups.
Project description:Objective To analyse stage specific incidence of breast cancer in the Netherlands where women have been invited to biennial mammography screening since 1989 (ages 50-69) and 1997 (ages 70-75), and to assess changes in breast cancer mortality and quantified overdiagnosis.Design Population based study.Setting Mammography screening programme, the Netherlands.Participants Dutch women of all ages, 1989 to 2012.Main outcome measures Stage specific age adjusted incidence of breast cancer from 1989 to 2012. The extra numbers of in situ and stage 1 breast tumours associated with screening were estimated by comparing rates in women aged 50-74 with those in age groups not invited to screening. Overdiagnosis was estimated after subtraction of the lead time cancers. Breast cancer mortality reductions and overdiagnosis during 2010-12 were computed without (scenario 1) and with (scenario 2) a cohort effect on mortality secular trends.Results The incidence of stage 2-4 breast cancers in women aged 50 or more was 168 per 100?000 in 1989 and 166 per 100?000 in 2012. Screening would be associated with a 5% mortality reduction in scenario 1 and with no influence on mortality in scenario 2. In both scenarios, improved treatments would be associated with 28% reductions in mortality. Overdiagnosis has steadily increased over time with the extension of screening to women aged 70-75 and with the introduction of digital mammography. After deduction of clinical lead time cancers, 33% of cancers found in women invited to screening in 2010-12 and 59% of screen detected cancers would be overdiagnosed.Conclusions The Dutch mammography screening programme seems to have little impact on the burden of advanced breast cancers, which suggests a marginal effect on breast cancer mortality. About half of screen detected breast cancers would represent overdiagnosis.