H.J. de Koning

Management of Lung Nodules Detected by Volume CT Scanning

BACKGROUND The use of multidetector computed tomography (CT) in lung-cancer screening trials involving subjects with an increased risk of lung cancer has highlighted the problem for the clinician of deciding on the best course of action when noncalcified pulmonary nodules are detected by CT. METHODS A total of 7557 participants underwent CT screening in years 1, 2, and 4 of a randomized trial of lung-cancer screening. We used software to evaluate a noncalcified nodule according to its volume or volume-doubling time. Growth was defined as an increase in volume of at least 25% between two scans. The first-round screening test was considered to be negative if the volume of a nodule was less than 50 mm(3), if it was 50 to 500 mm(3) but had not grown by the time of the 3-month follow-up CT, or if, in the case of those that had grown, the volume-doubling time was 400 days or more. RESULTS In the first and second rounds of screening, 2.6% and 1.8% of the participants, respectively, had a positive test result. In round one, the sensitivity of the screen was 94.6% (95% confidence interval [CI], 86.5 to 98.0) and the negative predictive value 99.9% (95% CI, 99.9 to 100.0). In the 7361 subjects with a negative screening result in round one, 20 lung cancers were detected after 2 years of follow-up. CONCLUSIONS Among subjects at high risk for lung cancer who were screened in three rounds of CT scanning and in whom noncalcified pulmonary nodules were evaluated according to volume and volume-doubling time, the chances of finding lung cancer 1 and 2 years after a negative first-round test were 1 in 1000 and 3 in 1000, respectively. (Current Controlled Trials number, ISRCTN63545820.)

Decreased rates of advanced breast cancer due to mammography screening in The Netherlands.

The effect of the implementation of the Dutch breast cancer screening programme during 1990–1997 on the incidence rates of breast cancer, particularly advanced breast cancer, was analysed according to stage at diagnosis in seven regions, where no screening took place before 1990. The Netherlands Cancer Registry provided detailed data on breast cancer incidence in 1989–1997 by tumour stage, age and region. Annual age-adjusted incidence rates of all breast cancers and advanced cancers, defined as large tumours T2+ with lymph node and/or distant metastases, were compared with rates in 1989. In general, breast cancer incidence rose strongly in the early 1990s, especially in the age category 50–69 years (estimated annual percentage change (EAPC) 4.25; 95% CI 1.70, 6.86). The increase was mainly due to the increase in small T1 cancers and ductal carcinoma in situ. However, in women aged 50–69, advanced cancer incidence rates showed a significant decline by 12.1% in 1997 compared with 1989 (EAPC –2.14, 95% CI −3.47, −0.80), followed by a breast cancer mortality reduction of similar size after approximately 2 years. We confirm that breast cancer screening initially leads to a temporary strong increase in the breast cancer incidence, which is followed by a significant decrease in advanced diseases in the women invited for screening. It is evident that breast cancer screening contributes to a reduction in advanced breast cancers and breast cancer mortality.

Anxiety and depression after prostate cancer diagnosis and treatment: 5-year follow-up

To document anxiety and depression from pretreatment till 5-year follow-up in 299 men with localized prostate cancer. To assess, if baseline scores were predictive for anxiety and depression at 1-year follow-up. Respondents completed four assessments (pretreatment, at 6 and 12 months, and at 5-year follow-up) on anxiety, depression and mental health. Respondents were subdivided according to therapy (prostatectomy or radiotherapy) and high vs low-anxiety. Pretreatment 28% of all patients were classified as ‘high-anxiety’; their average anxiety scores decreased significantly post-treatment, that is towards less anxiety. At all assessments, high-anxiety men treated by prostatectomy reported less depression than high-anxiety men treated by radiotherapy. Of men treated by radiotherapy, 27% reported clinical significant levels of depression while 20% is expected in a general population. The improvement in mental health at 6-months follow-up was statistically significant and clinically meaningful in all respondent groups. Sensitivity of anxiety at baseline as a screening tool was 71% for anxiety and 60% for symptoms of depression. We recommend clinicians to attempt early detection of patients at risk of high levels of anxiety and depression after prostate cancer diagnosis since prevalence is high. STAI-State can be a useful screening tool but needs further development.

Overdetection, overtreatment and costs in prostate-specific antigen screening for prostate cancer

Background:Prostate cancer screening with prostate-specific antigen (PSA) has shown to reduce prostate cancer mortality in the European Randomised study of Screening for Prostate Cancer (ERSPC) trial. Overdetection and overtreatment are substantial unfavourable side effects with consequent healthcare costs. In this study the effects of introducing widespread PSA screening is evaluated.Methods:The MISCAN model was used to simulate prostate cancer growth and detection in a simulated cohort of 100 000 men (European standard population) over 25 years. PSA screening from age 55 to 70 or 75, with 1, 2 and 4-year-intervals is simulated. Number of diagnoses, PSA tests, biopsies, treatments, deaths and corresponding costs for 100 000 men and for United Kingdom and United States are compared.Results:Without screening 2378 men per 100 000 were predicted to be diagnosed with prostate cancer compared with 4956 men after screening at 4-year intervals. By introducing screening, the costs would increase with 100% to [euro ]60 695 000. Overdetection is related to 39% of total costs ([euro ]23 669 000). Screening until age 75 is relatively most expensive because of the costs of overtreatment.Conclusion:Introduction of PSA screening will increase total healthcare costs for prostate cancer substantially, of which the actual screening costs will be a small part.

Short-term health-related quality of life consequences in a lung cancer CT screening trial (NELSON)

Background:In lung cancer CT screening, participants often have an indeterminate screening result at baseline requiring a follow-up CT. In subjects with either an indeterminate or a negative result after screening, we investigated whether health-related quality of life (HRQoL) changed over time and differed between groups in the short term.Methods:A total of 733 participants in the NELSON trial received four questionnaires: T0, before randomisation; T1, 1 week before the baseline screening; T2, 1 day after the screening; and T3, 2 months after the screening results but before the 3-month follow-up CT. HRQoL was measured as generic HRQoL (the 12-item Short Form, SF-12; the EuroQol questionnaire, EQ-5D), anxiety (the Spielberger State-Trait Anxiety Inventory, STAI-6), and lung-cancer-specific distress (the Impact of Event Scale, IES). For analyses, repeated-measures analysis of variance was used, adjusted for covariates.Results:Response to each questionnaire was 88% or higher. Scores on SF-12, EQ-5D, and STAI-6 showed no clinically relevant changes over time. At T3, IES scores that were clinically relevant increased after an indeterminate result, whereas these scores showed a significant decrease after a negative result. At T3, differences in IES scores between the two baseline result groups were both significant and clinically relevant (P<0.01).Conclusion:This longitudinal study among participants of a lung cancer screening programme showed that in the short term recipients of an indeterminate result experienced increased lung-cancer-specific distress, whereas the HRQoL changes after a negative baseline screening result may be interpreted as a relief.

Psychosocial predictors of first attendance for organised mammography screening.

Objective To study psychosocial predictors of attendance at an organised breast cancer screening programme. Setting Finnish screening programme based on personal first round invitations in 1992–94, and with 90% attendance rate. Methods Attenders (n=946) belonged to a 10% random sample (n=1680 women, age 50, response rate 64%) of the target population (n=16 886), non-attenders (n=641, 38%) came from the whole target population. Predictors were measured one month before the screening invitation. Measures included items for social and behavioural factors, Breast Cancer Susceptibility Scale, Illness Attitude Scale, Health Locus of Control Scale, Anxiety Inventory, and Depression Inventory. Univariate and multivariate logistic regression analyses were used to predict attendance. Results Those most likely to attend were working, middle income, and averagely educated women, who had not had a mass mammogram recently, but who regularly visited gynaecologists, attended for Pap smear screening, practised breast self examination, and who did not smoke. Low confidence in their own capabilities in breast cancer prevention, overoptimism about the sensitivity of mammography, and perception of breast cancer risk as moderate were also predictive of attendance. Expectation of pain at mammography was predictive of non-attendance. Conclusion Mammography screening organised as a public health service was well accepted. A recent mammogram, high reliance on self control of breast cancer, and an expectation of pain at mammography deterred attendance at screening. Further information about these factors and health information on screening are needed.

Changing role of 3 screening modalities in the European randomized study of screening for prostate cancer (Rotterdam)

A randomized screening trial was started in Europe to show the effect of early detection and treatment of prostate cancer on mortality (European Study on Screening of Prostate Cancer). In one centre (Rotterdam), the screening protocol initially consisted of 3 screening tests for all men: prostate‐specific antigen (PSA), digital rectal examination (DRE) and transrectal ultrasonography (TRUS). A PSA value of ≥4 ng/ml and/or an abnormality on DRE and/or TRUS were taken to indicate that biopsy was required. In this study, we examined the possibilities for a more efficient screening protocol. A logistic‐regression model was used to predict the number of cancers for PSA < 4 ng/ml if all men were biopsied (predictive index, PI). Effects of a change in PSA cut‐off on the screening results were explored. Weights were applied to procedures and cancers to explore the possibility of expressing differences between protocols in one overall figure. Biopsies in men with PSA < 1 ng/ml and a positive DRE or TRUS were very inefficient. Applying DRE and TRUS only in the PSA ranges 1.5 to 3.9 and 2 to 3.9 ng/ml to determine whether a biopsy was required would result in a decrease of 29 to 36% in biopsies and a decrease of 5 to 8% in cancers. However, the results of DRE and TRUS could not be duplicated entirely. A protocol with only PSA ≥ 3 ng/ml as a direct biopsy indicator resulted in a decrease of detected cancers by 7.6% and of biopsies by 12%, also a much simpler screening procedure. Use of the PI would give more efficient protocols, but this should be viewed as a preliminary finding, with the disadvantage of necessitating many additional screening visits. Since the results of DRE and TRUS could not be duplicated, a change in protocol towards PSA ≥ 3 ng/ml appears acceptable. If this proves effective, a final judgement about the optimal combination of screening tests may be made. Int. J. Cancer (Pred. Oncol.) 84:437–441, 1999.

Determining the cause of death in randomized screening trial(s) for prostate cancer

H.J. DE KONING, J. BLOM*, J.W. MERKELBACH†, R. RAAIJMAKERS‡, H. VERHAEGEN¶, P. VAN VLIET**, V. NELEN††, J.W.W. COEBERGH, A. HERMANS¶, S. CIATTO‡‡ and T. MÄKINEN Erasmus MC, Department Public Health, *Saint Franciscus Gasthuis, †Consultant Surgeon, Rotterdam, ‡Erasmus MC, Department of Urology, Rotterdam, the Netherlands, ¶Oncology Center Antwerp, Antwerp, **ACZA – campus St. Elisabeth, Department Urology, Antwerp, ††Prov. Institute voor Hygiene, Antwerp, Belgium, and ‡‡Centro per lo Studio e la Prevenzione Oncologica, Department Diagnostic Medical Imaging, Firenze, Italy

Interval cancers in the Dutch breast cancer screening programme.

The nationwide breast cancer screening programme in The Netherlands for women aged 50–69 started in 1989. In our study we assessed the occurrence and stage distribution of interval cancers in women screened during 1990–1993. Records of 0.84 million screened women were linked to the regional cancer registries yielding a follow-up of at least 2.5 years. Age-adjusted incidence rates and relative (proportionate) incidences per tumour size including ductal carcinoma in-situ were calculated for screen-detected and interval cancers, and cancers in not (yet) screened women, comparing them with published data from the UK regions North West and East Anglia. In total 1527 interval cancers were identified: 0.95 and 0.99 per 1000 woman-years of follow-up in the 2-year interval after initial and subsequent screens respectively. In the first year after initial screening interval cancers amounted to 27% (26% after subsequent screens) of underlying incidence, and in the second year to 52% (55%). Generally, interval cancers had a more favourable tumour size distribution than breast cancer in not (yet) screened women. The Dutch programme detected relatively less (favourable) invasive cancers in initial screens than the UK programme, whereas the number of interval cancers confirms UK findings. Measures should be considered to improve the detection of small invasive cancers and to reduce false-negative rates, even if this will lead to increasing referral rates.

Long-term effects of lung cancer computed tomography screening on health-related quality of life: the NELSON trial

The long-term effects of lung cancer computed tomography (CT) screening on health-related quality of life (HRQoL) have not yet been investigated. In the Dutch–Belgian Randomised Lung Cancer Screening Trial (NELSON trial), 1,466 participants received questionnaires before randomisation (T0), 2 months after baseline screening (screen group only; T1) and at 2-yr follow-up (T2). HRQoL was measured as generic HRQoL (12-item short-form questionnaire and EuroQoL questionnaire), anxiety (Spielberger State-Trait Anxiety Inventory) and lung cancer-specific distress (impact of event scale (IES)). Repeated measures of ANOVA were used to analyse differences between the screen and control groups, and between indeterminate (requiring a follow-up CT) and negative screening result groups. At T0 and T2 there were no significant differences in HRQoL scores over time between the screen and control groups, or between the indeterminate or negative second-round screening result group. There was a temporary increase in IES scores after an indeterminate baseline result (T0: mean 4.0 (95% CI 2.8–5.3); T1: mean 7.8 (95% CI 6.5–9.0); T2: mean 4.5 (95% CI 3.3–5.8)). At 2-yr follow-up, the HRQoL of screened subjects was similar to that of control subjects, the unfavourable short-term effects of an indeterminate baseline screening result had resolved and an indeterminate result at the second screening round had no impact on HRQoL.