Blinded and uniform causes of death verification in cancer screening: A major influence on the outcome of a prostate cancer screening trial?

BackgroundTo assess the agreement between the causes of death assigned by a blinded and uniform review panel of the Rotterdam section of the European Randomised Study of Screening for Prostate Cancer and the official vital statistics and to explore the possible effect of the use of either of these two sources on the outcome of the screening trial.MethodsA total of 670 deaths amongst men with prostate cancer, reviewed by the causes of death committee (CODC) up to 31st December 2006 were included in this study. The kappa statistics with confidence intervals (CI), sensitivity and specificity of the official statistics were determined, with the CODC considered the gold standard. The rate ratio (RR) and 95% confidence intervals (95% CI) for prostate cancer mortality, official statistics relative to CODC, were calculated following the Mantel–Haenszel procedure.ResultsThe overall concordance and the kappa between official statistics and the CODC were 90.6% and 0.76 (0.71–0.82), remaining comparable when only the CODC category definitely prostate cancer was applied, with the sensitivity of official statistics increasing from 88.3% to 91.3% and specificity hardly changing (91.3% and 90.5%). High specificity and lower sensitivity is observed in the screening arm, whilst the opposite was seen in the control arm in men aged 55–69 and 70–74 years at entry. Considerable lower false positive rate was seen for both age groups in the screening arm (3.9% and 4.7%) compared to the control arm (8.4% and 14.3%). A statistically significant excess of prostate cancer death was observed for the official statistics in the age group 70–74 years, 1.53 (1.07–2.19), whilst it was not significant for men aged 55–69 at entry, 1.06 (0.83–1.36).ConclusionIn the Rotterdam ERSPC section, official statistics tended to overreport prostate cancer as an underlying cause of death, particularly in the age group 70-plus in the control arm, which would overestimate the true effect in favour of screening.     

Systematic reviews as a ‘lens of evidence’: Determinants of benefits and harms of breast cancer screening

This systematic review, stimulated by inconsistency in secondary evidence, reports the benefits and harms of breast cancer (BC) screening and their determinants according to systematic reviews. A systematic search, which identified 9,976 abstracts, led to the inclusion of 58 reviews. BC mortality reduction with screening mammography was 15–25% in trials and 28–56% in observational studies in all age groups, and the risk of stage III+ cancers was reduced for women older than 49 years. Overdiagnosis due to mammography was 1–60% in trials and 1–12% in studies with a low risk of bias, and cumulative false-positive rates were lower with biennial than annual screening (3–17% vs 0.01–41%). There is no consistency in the reviews’ conclusions about the magnitude of BC mortality reduction among women younger than 50 years or older than 69 years, or determinants of benefits and harms of mammography, including the type of mammography (digital vs screen-film), the number of views and the screening interval. Similarly, there was no solid evidence on determinants of benefits and harms or BC mortality reduction with screening by ultrasonography or clinical breast examination (sensitivity ranges, 54–84% and 47–69%, respectively), and strong evidence of unfavourable benefit-to-harm ratio with breast self-examination. The reviews’ conclusions were not dependent on the quality of the reviews or publication date. Systematic reviews on mammography screening, mainly from high-income countries, systematically disagree on the interpretation of the benefit-to-harm ratio. Future reviews are unlikely to clarify the discrepancies unless new original studies are published.     

Who should be included in a clinical trial of screening for bladder cancer?

BACKGROUND:

Because of its relatively low incidence, bladder cancer screening might have a better ratio of benefits to harms if it is restricted to a high‐risk population. Data from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial were used and simple decision analytic techniques were applied to compare different eligibility criteria for a screening trial.

METHODS:

For a variety of possible eligibility criteria, the percentage of the population aged 55 years to 74 years and classified as being at high risk for developing invasive or high‐grade carcinoma, and therefore likely to benefit from screening, was calculated. Regression models were used to calculate a risk score based on age, sex, smoking history, and family history of bladder cancer. The reduction in cases was calculated given hypothetical risk reductions associated with screening. The trade‐off between patients screened and tumors avoided was calculated as a net benefit.

RESULTS:

The 5‐year probability of being diagnosed with invasive bladder cancer was 0.24%. Using a risk score > 6 or > 8 as the eligibility criterion for a trial was generally superior to including all older adults. In a typical scenario, a risk score > 6 would result in approximately 25% of the population being screened to prevent 57 invasive or high‐grade bladder cancers per 100,000 population; screening the entire population would prevent only an additional 38 cases.

CONCLUSIONS:

Screening for bladder cancer can be optimized by restricting it to a subgroup of patients considered to be at elevated risk. Different eligibility criteria for a screening trial can be compared rationally using decision‐analytic techniques. Cancer 2013. © 2012 American Cancer Society.     

Cervical cancer screening for high risk women: is it possible? Results of a cervical cancer screening program in three suburban districts of Lyon]

Between november 1993 and october 1996, a cervical screening program was proposed for women 25-65-year-old who tend to have little or no medical supervision, in three suburban districts of Lyon. The data and results of the two last Pap-smears have been collected together with details of gynecological follow-up. Both general practitioners and gynaecologists were actively involved. A total of 3,792 women (12.3% of the target) were registered, with a larger proportion of women over 60 (17.7%). According to the "Consensus of Lille", only 403 women (34.4%) had adequate screening (over 50 y: 25.8%, 35-49 y: 39.4%, 25-35 y: 36.5%) and 2,489 women had inappropriate gynaecological follow-up: no smear for 185 women (4.9%) and inadequate schedule of follow-up visits for 476 others (12.5%). Missing data (date or results of Pap smear) were noted for 1,828 patients (48.2%). The screening procedure for women over 50 years was carried out mainly by general practitioner. Of 3,127 registered smears, 62 positive results were found (2.1%). Of these women, 9 were lost to follow-up and 4 did not have appropriate tests. Others results were: 27 negative further investigations, 9 CIN1, 7 CIN2, 3 CIN3, 1 in situ carcinoma and 2 invasive carcinoma. Despite low participation, this pilot study indicates that a procedure can be established to integrate high risk women in cervical cancer screening programme. Active participation of general practitioners is essential.     

Is the progesterone test a generalizable method of screening for neoplastic and preneoplastic lesions of the endometrium?

A "progesterone test" has recently been proposed as a tentative method to detect early neoplastic and pre-neoplastic lesions of the uterus endometrium. At the time progesterone is stopped, a "deprivation" metrorragia demonstrates a remanent hyperoestrogenism, which represents a well-known risk factor for this type of lesion. The method has been evaluated in private practice; 389 patients were offered the test: 87% accepted. Metrorragias were observed in 28% of the cases; however, no neoplastic nor pre-neoplastic lesions could be detected in this group of patients. Moreover, one patient presented with an advanced endometrial cancer one year after a negative test. The reliability of such a test clearly needs further evaluation.     

Assessment of breast cancer opportunistic screening by clinical�Cpathological indicators: a population-based study

Background:

Although some clinical–pathological features of breast cancers, such as the incidence of ductal cancer in situ (DCIS) and the diameter of invasive tumours, are sensitive indicators of early detection, comprehensive population-based studies of opportunistic screening are needed.

Methods:

Cases of DCIS or invasive breast cancer diagnosed in 1996–2007 were identified from the Ticino Cancer Registry (south of Switzerland). Time trends of age-adjusted incidence and mortality, as well as main clinical–pathological features, such as tumour diameter, AJCC stage and histological grade, were analysed.

Results:

A total of 3047 incident cases of female breast cancer were identified. The proportion of DCIS with respect to invasive cases increased from 5.8% in the period 1996–2001 to 6.4% in the period 2002–2007. The median tumour size of invasive cancers decreased from 20 mm in 1996–2001 to 18 mm in 2002–2007 (P<0.0001). An increase in well/moderately differentiated invasive tumours, from 67% in the period 1996–2001 to 73% in 2002–2007 (P<0.001), was detected and resulted in an Annual Percentage Change of incidence of 2.8 (95% confidence interval: 1.3; 4.3).

Conclusion:

An opportunistic screening strategy can lead to an improvement of prognostic features at diagnosis, but these features are still less favourable than those achieved by organised screening programmes.     

Prostate specific antigen: a useful screening test?

The role of prostate specific antigen (PSA) as a screening test for prostate cancer is controversial. Proponents of screening emphasize that early detection can lead to discovery of organ-confined disease and the potential for cure. Opponents point to the lack of credible evidence that screening is associated with a decrease in mortality. In addition, population-based screening (with subsequent diagnosis and treatment in many men) can be associated with considerable morbidity and mortality in the context of a disease that is often not fatal. This report examines the limitations of PSA as a screening test and supports an approach using "verbal informed consent" to identify patients who should be tested.     

Sociodemographic predictors of non-attendance at invitational mammography screening – a population-based register study (Sweden)

Objective: To investigate the role of sociodemographic factors in predicting mammography uptake in an outreach screening program. Methods: Linkage of data from a regional population-based mammography program with four Swedish nationwide registers: the Population and Housing Census of 1990, the Fertility Register, the Cancer Register, and the Cause of Death Register. We computed odds ratios (OR) and 95% confidence intervals (CI) for non-attendance by sociodemographic factors. Non-attendance was defined as failure to attend in response to the two most recent invitations. Results: Multivariate analyses among 4198 non-attenders and 38,972 attenders revealed that both childless and high-parity women were more likely to be non-attenders (OR = 1.8, 95% CI: 1.6–2.0 and OR = 2.2, 95% CI: 1.8–2.7, respectively). Women living without a partner were less likely to attend (OR = 1.7, 95% CI: 1.5–1.9), as were non-employed women (OR = 2.1, 95% CI: 1.9–2.3). Those renting an apartment were more likely to be non-attenders compared with home-owners (OR = 1.8, 95% CI: 1.6–2.0), and immigrants from non-Nordic countries were more than twice as likely to be non-attenders compared with Swedish-born women (OR = 2.4, 95% CI: 2.0–2.8). Conclusions: There are identifiable subgroups in which mammography utilization can be increased. Special attention should be paid to women who have never attended, childless women, and non-Nordic immigrants.     

'Should a mammographic screening programme carry the warning: screening can damage your health!'?

The balanced presentation afforded by convening a Citizens' Jury when considering a major question such as the introduction of a breast screening programme is advocated. This method would enable account to be taken of all the costs, both human and financial, to all those affected, both participating and organizing, as well as the benefits. Provision of such a democratic opportunity enables consideration to be given to a broad range of factors, by selection of an appropriate range of witnesses, with the advantage of involving the lay public in this decision-making process. Attendance by health correspondents, medical journalists and other media representatives enables publicization of a democracy in action whilst helping to inform the wider debate. Such an exercise could inform whether the NHS BSP should continue in its current form.     

Cervical cancer case–control audit: Results from routine evaluation of a nationwide cervical screening program

Our study used a refined case–control cervical cancer Audit framework to investigate effectiveness of cervical screening, with measures of three screening failures: irregular-participation, cervical cancer developed after cytological abnormalities and after normal screening results. The register-based study included 4,254 cervical cancer cases diagnosed in Sweden during 2002–2011, and 30 population-based controls per case. We used conditional logistic regression models to examine relative risks of cervical cancer in relation to screening participation and screening results in the past two screening rounds from 6 months before cancer diagnosis. We found that women unscreened in past two screening rounds showed four times increased risk of cervical cancer compared to women screened in time (OR = 4.1, 95% CI = 3.8–4.5), and women unscreened in the previous round but screened in the most recent round also showed a statistically significantly elevated risk (OR = 1.6, 95% CI = 1.5–1.8). Women having abnormality in previous two rounds exhibited higher risk of cervical cancer compared to women screened with normal results, while having normal results in the subsequent round after the abnormality also yielded an increased risk (OR = 4.0, 95% CI = 3.2–5.1). Being screened with only normal results was associated with 89% risk reduction for squamous cell cancer, compared to women unscreened, but only 60% reduction for adenocarcinoma. Our findings emphasize the importance of routine participation in cervical screening and suggest that management of abnormalities, as well as sensitivity of the test, warrants improvement especially for preventing cervical adenocarcinoma. The Audit framework serves as routine evaluation model and the findings benchmark for future evaluation of changes in screening practice.     

Nonattendance in mammographic screening: a study of intraurban differences in Malmö, Sweden, 1990-1994

Mammographic screening may reduce breast cancer mortality. Not all women, however, come for examination. The objective in this study from Malm? has been to assess extent to which the rate of nonattendance varies between residential areas with different sociodemographic profiles. The study is based on 32,605 women, 45 to 68 years old and living in 17 areas, who between 1990 and 1994 were invited to screening. Between age groups, the age-specific nonattendance rate ranged from 31% to 35 % (P < .01). The nonattendance rate was highest for women 65 years or older. Between residential areas, age-adjusted nonattendance rates ranged from 23% to 43% (P < .01). A socioeconomic score was developed to express the socioeconomic circumstances in the residential areas and ranged from -7.18 in the most deprived area to 5.01 in the least. Nonattendance covaried in an inverse fashion with the socioeconomic score (r = -0.78; P < .01). One of three women in this urban population did not accept the invitation to mammographic screening. Our conclusion is that women in areas with less favorable circumstances seem to be less willing to participate.     

Analysis and classification of interval cancers in a French breast cancer screening programme (département of Isère).

The objective of this study is to analyse detection rates and stage of diagnosis of interval cancers in the mass screening mammography programme of Isère (France), launched in 1990. Interval cancers are defined as breast cancers diagnosed within 30 months after a negative screening assessment, for women attending the programme between November 1990 and December 1994. Stages of diagnosis of these cancers are compared with those of screened cancers and to those of cancers diagnosed outside the programme. The rates of invasive interval cancers are 17.7% of the expected incidence rate during the first year, 60.0% during the second year and 58.8% after the second year. Sensitivity of the programme (one test every 30 months) is 74%; sensitivity at one year is 82%. Results are better for women aged 60-69 years than for younger women (50-59 years). Diagnosis is made at an early stage with 8% of in situ cases, and with 40% of very small tumours (sizes < or = 10 mm). Those stages are very close to the ones for screened cases. Interval cancer rates are low during the first year. Higher rates for the second year and early stages of diagnosis could be explained by self-referred screening practice in our area.     

Does a standard measure of self‐reported physical disability correlate with clinician perception of impairment related to cancer screening?

BACKGROUND:

Adults with physical disabilities are less likely than others to receive cancer screening. It is not known, however, whether commonly used measures assess elements of physical ability necessary for successful screening. The objective of this exploratory study was to determine whether patients who reported limitations in activities of daily living (ADLs) or instrumental ADLs (IADLs) are perceived by their primary care clinicians to have physical limitations that may impede cancer screening.

METHODS:

Patients at 2 rural primary care clinics were surveyed about ADLs and IADLs and about their up‐to‐date status for breast, cervical, and/or colorectal cancer screening. Clinicians and office staff were asked whether they believed each patient had a physical limitation that might impede screening. The agreement between patient and clinician assessments was evaluated.

RESULTS:

Clinicians believed that 43% of patients with severe disability (ADLs) and 30% of patients with moderate disability (IADLs) had limitations that might affect screening. Agreement between patient and clinician assessments was low according to the kappa statistic (κ = 0.355), but had a high percentage of negative agreement (92.3%) and a low percentage of positive agreement (42.7%). Patients with ADL/IADL‐related disability were less likely than nondisabled patients to be current for cervical and breast cancer screening. Patients who were viewed by clinicians as having limitations relevant for screening were less likely to be current for cervical cancer screening.

CONCLUSIONS:

These results indicate that a common measure of general disability may not capture all factors relevant for cancer screening. An instrument designed to include these factors may help identify and accommodate patients who have disabilities that may impede screening. Cancer 2012;. © 2011 American Cancer Society.     

Cervical cancer in the screening era: who fell victim in spite of successful screening programs?

Objective

To compare profiles of a prescreening and screening cohort of women with cervical cancer regarding histopathology and clinical variables in order to identify those remaining at risk despite successful screening programs. By analyzing these profiles we hope to improve future screening methods.

Methods

The prescreening and screening cohorts consisted of 5,046 and 1,174 women, respectively, treated for cervical cancer at the Department of Gynecological Oncology at Radiumhemmet, Karolinska University Hospital, during the periods 1944-1957 and 1990-2004.

Results

Mean age increased from 48.9 years to 55.3 years in the cohorts treated 1944-1957 and 1990-2004, respectively. The percentage of patients older than 69 years was 5.4% and 27.3% in the prescreening and screening period, respectively. A shift towards earlier stages at diagnosis, a reduction of squamous cervical cancer and an increase of adenocarcinoma were observed in the screening cohort. The percentage of adenocarcinoma was about 6 times higher among younger patients. Cases of stump cancer and cervical cancer associated with pregnancy have declined. Eighty-seven women in the screening cohort had a history of treatment for in situ carcinoma by conization; 28% of these cases developed cervical cancer within one year after conization.

Conclusion

The profile changed in the screening era indicating a need to refine screening for improved detection of in older women. This study, one of the largest clinical series of cervical cancer, provides an important baseline with which later studies can be compared to evaluate the effects of human papillomavirus vaccine and other important changes in this field.