Short-Term Effects of Population-Based Screening for Prostate Cancer on Health-Related Quality of Life

JNCI Journal of the National Cancer Institute, Jun 1998

Background. Population-based screening for prostate cancer is currently being evaluated in randomized clinical trials in the United States and in Europe. Side effects arising from the process of screening and from the earlier treatment of screen-detected prostate cancer may be important factors in the evaluation. To examine health-related quality of life (or health status) among men screened for prostate cancer, we conducted a longitudinal study of 626 attenders to the Rotterdam (The Netherlands) prostate cancer screening program and of 500 nonparticipants. Methods: Attenders of the screening program and nonparticipants completed self-assessment questionnaires (SF-36 [i.e., Medical Outcomes Study 36-Item Short-Form Health Survey] and EQ-5D [i.e., EuroQol measure for health-related quality of life] health surveys) to measure generic health status, as well as an additional questionnaire for anxiety and items relating to prostate cancer screening. Results: Physical discomfort during digital rectal examination and during transrectal ultrasound was reported by 181 (37%) of 491 men and by 139 (29 %) of 487 men, respectively; discomfort during prostate biopsy was reported by 64 (55%) of 116 men. Mean scores for health status and anxiety indicated that the participants did not experience relevant changes in physical, psychological, and social functioning during the screening procedure. However, high levels of anxiety were observed throughout the screening process among men with a high predisposition to anxiety. Similar scores for anxiety predisposition were observed among attenders and nonparticipants. Conclusions: At the group level, we did not find evidence that prostate cancer screening induced important shortterm health-status effects, despite the short-lasting side effects related to the biopsy procedure. However, subgroups may experience high levels of anxiety. The implication is that unfavorable health-status effects of prostate cancer screening occur mainly in the treatment phase. [J Nall Cancer Inst 1998; 90:925-31]

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://jnci.oxfordjournals.org/content/90/12/925.full.pdf

Short-Term Effects of Population-Based Screening for Prostate Cancer on Health-Related Quality of Life

Journal of the National Cancer Institute Marie-Louise Essink-Bot 0 2 3 Harry J. de Koning 0 2 3 Hubert G. T. Nijs 0 2 3 Wim J. Kirkels 0 2 3 Paul J. van der Maas 0 2 3 Fritz H. Schr oder 0 1 2 3 0 Oxford University Press 1 Affiliations of authors: M. L. Essink-Bot, H. J. de Koning , P. J. van der Maas , Department of Public Health, Erasmus University Rotterdam , The Nether- lands; H. G. T. Nijs , Department of Health Policy and Management, Erasmus University Rotterdam, and Department of Health Promotion, Municipal Health Services, Rotterdam Area; W. J. Kirkels, F. H. Schro der, Department of Urology, Erasmus Uni- versity Rotterdam, and Academic Hospital , Rotter- dam. M.D., Ph.D. , Department of Public Health, Erasmus University Rotterdam , P.O. Box 1738, 3000 DR Rotterdam , The Netherlands 2 Journal of the National Cancer Institute , Vol. 90, No. 12, June 17, 1998 3 Present address: M. L. Essink-Bot, Institute for Medical Technology Assessment, Erasmus Univer- sity Rotterdam, The Netherlands. Present address: H. G. T. Nijs, Municipal Health Services Zuid-Holland Zuid , Dordrecht , The Neth- erlands. We thank the personnel of the Department of Urology at the University Hospital Rotterdam for administrative support and all respondents for par- ticipating in this study. We also thank Joanna B. Madalinska for her valuable comments on an earlier version of this manuscript. Manuscript received November 26 , 1997; revised March 17, 1998; accepted April 7, 1998 - Background: Population-based screening for prostate cancer is currently being evaluated in randomized clinical trials in the United States and in Europe. Side effects arising from the process of screening and from the earlier treatment of screen-detected prostate cancer may be important factors in the evaluation. To examine health-related quality of life (or health status) among men screened for prostate cancer, we conducted a longitudinal study of 626 attenders to the Rotterdam (The Netherlands) prostate cancer screening program and of 500 nonparticipants. Methods: Attenders of the screening program and nonparticipants completed self-assessment questionnaires (SF-36 [i.e., Medical Outcomes Study 36-Item Short-Form Health Survey] and EQ-5D [i.e., EuroQol measure for health-related quality of life] health surveys) to measure generic health status, as well as an additional questionnaire for anxiety and items relating to prostate cancer screening. Results: Physical discomfort during digital rectal examination and during transrectal ultrasound was reported by 181 (37%) of 491 men and by 139 (29%) of 487 men, respectively; discomfort during prostate biopsy was reported by 64 (55%) of 116 men. Mean scores for health status and anxiety indicated that the participants did not experience relevant changes in physical, psychological, and social functioning during the screening procedure. However, high l e v e l s o f a n x i e t y w e r e o b s e r v e d throughout the screening process among men with a high predisposition to anxiety. Similar scores for anxiety predisposition were observed among attenders and nonparticipants. Conclusions: At the group level, we did not find evidence that prostate cancer screening induced important shortterm health-status effects, despite the short-lasting side effects related to the biopsy procedure. However, subgroups may experience high levels of anxiety. The implication is that unfavorable health-status effects of prostate cancer screening occur mainly in the treatment phase. [J Natl Cancer Inst 1998; 90:92531] Prostate cancer screening is currently being evaluated in two large randomized trials, i.e., the European Randomized Study of Screening for Prostate Cancer and the screening trial for prostate, lung, colorectal, and ovarian cancers in the United States (14). Provided that a decrease in prostate cancer mortality as a result of screening will ultimately be shown, the crucial question is whether this benefit outweighs the inevitable unfavorable side effects of population-based cancer screening. Unfavorable side effects on healthrelated quality of life (or health status) may occur during the screening procedure itself (e.g., pain, discomfort, and feelings of uncertainty and distress). Furthermore, health-status effects of cancer screening can be found in the treatment phase. Subjects with screen-detected cancer are labeled as cancer patients and treated earlier than if there had been no screening. At the population level, cancer screening causes an increase in the number of life-years lived with side effects of primary treatment (5). However, if prostate cancer mortality decreases as a result of screening, the incidence of end-stage disease decreases accordingly. At the population level, the decrease in prostate cancer mortality will result in a decrease in the time lived in the bad health states associated with end-stage cancer. This result constitutes a favorable effect on health status of population-based screening (6). All of the health-status effects mentioned above contribute to the ultimate balance of advantageous and disadvantageous public health effects of a cancer screening program (7). This report describes an empirical study on the short-term health-status effects of the prostate cancer screening process itself. Three research questions will be answered: 1) To what extent is the generic health status of participants in the short term affected by either the initial screening tests or the biopsy procedure? 2) Are there any specific effects relating to emotional distress? 3) Is there any support for psychological self-selection among nonparticipants? Subjects and Methods The Rotterdam Screening Trial for Prostate Cancer Six European centers have participated in the European Randomized Study of Screening for Prostate Cancer. The trial will provide an empirical answer to the question of whether screening in men in the 55to 69-year-old age group reduces prostate cancer mortality. The ongoing Rotterdam trial was begun in June 1994 and was preceded by a number of pilot studies (8). The screening protocols in the centers participating in the European Randomized Study of Screening for Prostate Cancer are slightly different. In Rotterdam (P6 protocol), men in the 55- to 74year-old age group were identified in municipal population registries (with 100% coverage) and invited by mail to participate in the trial. Their letter of invitation included general information regarding prostate cancer screening and the trial as well as an informed consent form. After providing written informed consent to the screening bureau, the men were randomly and individually assigned by computer to either the screening arm or the control arm of the trial. The men in the control arm were informed about their control status. Since the start of the P6 protocol, 8639 men (43% of eligible men) have participated in the trial. Men who were randomly assigned to the screening arm were invited for screening. At the screening center, they provided a venous blood sample for prostate-specific antigen (PSA) testing. Subsequently, digital rectal examination and transrectal ultrasound were performed (both by the same person per attender). The PSA result was not available when the other tests were performed. An additional appointment for prostate biopsy was scheduled if the PSA level equaled 4 ng/mL or more or if either one of the other tests gave a suspicious result. If applicable, attenders were requested to discontinue aspirin or oral anticoagulant therapy 10 days before the prostate biopsy was performed. All candidates for a biopsy took preventive antimicrobial therapy 2 hours before the procedure and 4 hours after its completion. A sextant transrectal prostate biopsy was performed (and at the lesion, if visible by transrectal ultrasound). The urologist informed each man about the result approximately 2 weeks after the biopsy was performed. A comprehensive cost-effectiveness analysis has been conducted alongside the randomized screening trial. This analysis included health-status assessments in the relevant phases of the screening and the treatment path. The screening trial, the cost-effectiveness analysis, and the health-status study were approved by the Medical Ethical Committee of the Academic Hospital in Rotterdam, The Netherlands. Approval for the prostate screening program and the screening trial was obtained from the Minister of Health and the Health Council, as required by the Population Screening Act (The Netherlands, 1992). Hypotheses and Design of the Study on the Short-Term Health-Status Effects of Prostate Cancer Screening A number of hypotheses were formulated at the start of the study. First, we did not expect to find, on average, relevant effects of the screening procedure itself on the generic health status. Second, an increased level of anxiety (above the age- and sexadjusted reference scores) among attenders to the screening was expected to be found immediately preceding the initial screening tests, whereas the average anxiety level was expected to return to normal after the subject was informed that all was well. Furthermore, the prostate biopsy was expected to be a stressful event. Even higher levels of anxiety were expected to be measured in the subjects who had undergone a biopsy procedure recently and were waiting to be informed about the results. The high anxiety levels of these subjects were expected to return to normal after they received the message that they did not have cancer. Third, we assumed that men with a predisposition to react with high anxiety levels to a stressful event (such as cancer screening) would be more likely not to respond to the invitation to the screening trial. Such behavior could then tentatively be explained as a method employed to reduce the stress of the receipt of the invitation and prevent the anticipated levels of distress induced by the screening itself. If it could be shown that nonparticipants differ from attenders with respect to the predisposition to anxiety, this could lend support to the hypothesis of psychological self-selection among nonparticipants in a prostate cancer screening program. Two groups of men were approached for empirical health-status measurement: attenders and nonparticipants. The first group (attenders) had provided written informed consent to participate in the screening trial and had been randomly assigned into the screening arm. Health-status data were longitudinally collected (Fig. 1). A sample of 626 men who were consecutively invited for screening during the period from September 1995 through March 1996 received the first questionnaire by mail, approxi926 REPORTS mately 3 weeks before the scheduled visit to the screening center (time 1 or T1). The second assessment (time 2 or T2) took place in the waiting room at the screening center directly preceding the screening (venous blood sampling for PSA testing, digital rectal examination, and transrectal ultrasound). Men for whom the results of the initial screening tests were unsuspicious and for whom a prostate biopsy was deemed to be unnecessary were asked to complete a health-status questionnaire at time 3 (T3), 1 week after they were informed about this result. Men with a PSA level of 4 ng/mL or more and/or suspicious results of either of the other tests were offered a biopsy procedure, and they were asked to complete a questionnaire at time 4 (T4), i.e., during the 2-week period between the biopsy and the visit to the outpatient clinic in which the man was informed about the biopsy result. The men who received the message that prostate cancer was not confirmed by the biopsy result (i.e., false-positive initial screening result) completed another questionnaire at time 5 (T5), i.e., 1 week after they received the message that they did not have cancer. Patients with screen-detected cancer did not receive the T5 questionnaire of the present study because the healthstatus impact of prostate cancer and its various treatment modalities are the subjects of a separate ongoing longitudinal study. Reminder cards were sent to nonrespondents at T3 and T5, respectively, 2 weeks after distribution of the initial questionnaire. Reminder procedures were not feasible because of time constraints at the other assessments. In summary, the attenders completed questionnaires at T1 (baseline) and T2 (waiting room) and either at T3 (when nothing suspicious was found in the initial screening tests) or at T4 (during the waiting period for the biopsy result) and T5 (after being informed that the biopsy result did not confirm a prostate cancer diagnosis). The second group of men approached for empirical health-status assessment (nonparticipants) consisted of men who did not respond to the initial invitation to participate in the trial. A random selection of 500 nonparticipants who had been invited during the period from September 1995 through March 1996 received a questionnaire by mail in July 1996. Reminders were sent to all nonrespondents at 2 and 4 weeks after the initial mailing. Health-Status Measures Health-related quality of life (or health status) was defined as the functioning of subjects in the physical, psychological, and social domains. Two generic, i.e., comprehensive and non-disease-specific, health-status measures (SF-36 [i.e., Medical Outcomes Study 36-Item Short-Form Health Survey] and EQ-5D [i.e., EuroQol measure for health-related quality of life]) were supplemented by a specific measure for anxiety (the StateTrait Anxiety Inventory [STAI]) and self-developed items on specific consequences and the experiences of the various screening tests. More complete descriptions of these measures are given below. The SF-36 was developed in the United States in the late 1980s as part of the Medical Outcomes Study (911), a longitudinal investigation of the self-reported health status of patients with a range of chronic conditions. It consists of 36 items, organized into eight scales (physical functioning [10 items], role limitations due to physical problems [rolephysical; four items], bodily pain [two items], general health perceptions [five items], vitality [four items], social functioning [two items], role limitations due to emotional problems [role-emotional; three items], and mental health [five items]). One item on health change that is scored separately is not reported on in this paper. The number of response choices per item ranges from two to six. Each scale yields a score in the range from 0 (the worst possible score) to 100 (the best possible score) (9). Differences of 6.5 points in the physical dimensions and 7.9 points in the mental dimensions of the SF-36 are thought by its authors to be clinically meaningful (10). Furthermore, two summary measures can be computed that aggregate scales: the physical component summary and the mental component summary. These summary scales were constructed so that they have a mean score of 50 (25th75th percentile score interval, 4356) for the general population in the United States (10,11). The Dutch version of the SF-36 employed in the current study was developed as a part of the International Quality of Life Assessment Project, whose objective was to translate, adapt, and validate the SF-36 for use in some 15 countries (12). We used the version that utilizes a time frame (reference period) of 1 week. The EQ-5D measure for health-related quality of life was developed by the EuroQol Group as a generic five-item classification (13). The EuroQol Group is a multidisciplinary and originally European group of researchers, with current members from centers in the U.K, The Netherlands, Spain, Germany, Denmark, Finland, Sweden, Greece, the United States, and Canada. The standard Dutch EQ5D was used (14). It consists of five items regarding mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, with each item having three levels: 1 4 no problems, 2 4 some problems, and 3 4 extreme problems. For reasons of brevity, these items are not described in this report. Furthermore, respondents are asked to rate their own health directly on a visual analogue scale ranging from 0 (labeled as worst imaginable health state) to 100 (labeled as best imaginable health state). The STAI is a U.S. 40-item questionnaire, of which a validated Dutch version is available (15 17). It consists of two separate parts of 20 items each. The first, the state part, measures temporary anxiety as occurring in reaction to specific situations. The second, the trait part, intends to measure a stable personality characteristic, i.e., a persons predisposition to react with high anxiety levels to anxiety-provoking situations. A subject with a high trait anxiety score will generally be more anxious in a specified situation (e.g., prostate cancer screening) than a subject with a low trait anxiety score in the same situation. State anxiety scores range from 20 (lowest possible anxiety score) to 80 (highest possible anxiety score). Similarly, the score range of the trait anxiety is limited by 20 (lowest possible predisposition to anxiety ) to 80 (highest possible predisposition to anxiety). Screening-specific items. Subjects were retrospectively asked to grade pain and physical discomfort, respectively, experienced during the venous blood sampling for PSA testing, digital rectal examination, transrectal ultrasound, and, if relevant, prostate biopsy, respectively, on 3-point Likert scales at T3 or T5. Biopsy-specific items relating to symptoms experienced in the week after the biopsy Fig. 1. Flow chart describing the cohort of men invited to participate in the Rotterdam part of the European Randomized Study of Screening for Prostate Cancer during the period from September 1995 through March 1996. Vertical arrows show the timing of the health-status assessments. Health-status measures used and numbers of usable response are indicated. SF-36 4 Medical Outcomes Study 36-Item Short-Form Health Survey; EQ-5D 4 EuroQol measure for health-related quality of life; STAI 4 StateTrait Anxiety Inventory; PSA 4 prostate-specific antigen. Timing of the health-status assessments: T1 4 baseline, approximately 3 weeks before screening; T2 4 in the waiting room before screening; T3 4 1 week after being notified about the unsuspicious results of the initial screening tests, no biopsy needed; T4 4 during the 2-week period between the biopsy procedure and the result while waiting for biopsy result; T5 4 1 week after being notified that prostate cancer was not confirmed by the biopsy result. and their consequences were included in the questionnaire at T4. Limitations as a result of the biopsy in daily activities, social activities, and sex life in the week after the biopsy were graded on 5-point Likerttype scales with labeled end points, no limitations at all and extremely limited. Demography and morbidity. Information on age, marital status, educational level, and employment status was obtained. Educational level was classified as low (primary school or lower technical education), high (college/university degree), or intermediate. Morbidity was assessed by the standard list of chronic conditions from the Dutch Bureau for Statistics (CBS; located in Voorburg, The Netherlands) that enumerates 28 conditions in lay terms (e.g., asthma, chronic bronchitis, or chronic obstructive pulmonary disease and diabetes). Respondents were asked whether they had any of these conditions, either currently or during the previous year. Presentation of the Questionnaires The questionnaires presented to the attenders at various time points and to the nonparticipants are shown in Fig. 1. Statistical Analysis Missing values for the items of the SF-36 were imputed following the guidelines in the SF-36 Health Survey Manual (9). Missing values for the items of the other instruments (EQ-5D, STAI, and screening-specific items) were not imputed. Mean values are presented as the measure of central tendency in the scores observed for the SF-36 scales, state anxiety, trait anxiety, EQ-5D self-rated health, and demographic characteristics with interval properties (age and number of chronic conditions). The dispersion observed in these scores is presented by the interval bounded by the 25th and the 75th percentile scores. The two-sided t test for dependent samples was used to test differences between T3 (after unsuspicious results of initial prostate cancer screening tests) and T1 (baseline) mean SF-36 scale scores and EQ-5D self-rated health scores of attenders who underwent only the initial screening tests. Similarly, the two-sided t test for dependent samples was used to test differences between mean SF-36 scale scores and mean EQ-5D self-rated health scores at T5 (after notice that prostate cancer was not confirmed by biopsy) and at baseline (T1) of attenders who underwent a screening including a biopsy procedure. Differences in mean scores for the state anxiety, trait anxiety, and EQ-5D self-rated health assessments at various time points were tested by the same procedure. Mean difference scores and 95% confidence intervals of the differences were computed for SF-36 scale scores and EQ-5D self-rated health scores of the group who underwent screening without biopsy (T3 T1) and with biopsy (T5 T1), respectively. Similarly, mean difference scores and 95% confidence intervals of the differences were computed for state anxiety and trait anxiety scores (T3 T2, procedure without biopsy; T4 T2 and T5 T4, procedure with biopsy). Differences between the attenders and the nonparticipants were assessed with descriptive statistics, and no statistical tests were performed. All P values resulted from the use of two-sided statistical tests. Analyses were conducted with SPSS 6.1 for Windows (SPSS Inc., Chicago, IL) or GLIM (Royal Statistical Society, London, U.K.). Changes in Attenders Health-Related Quality of Life The numbers of usable questionnaires returned from men eligible for participation in the study were as follows: at T1, 600 (96%) of 626 questionnaires; at T2, 555 (96%) of 581 questionnaires; at T3, 381 (86%) of 442 questionnaires; at T4, 160 (98%) of 164 questionnaires; and at T5, 116 (89%) of 130 questionnaires. At T2, T3, and T4, for unintentional, organizational reasons, 45, 15, and five eligible men, respectively, did not receive a questionnaire. The attenders had a mean age of 63.2 years (25th75th percentile score interval, 59.066.8 years); 88% were married; 63% were pensioners; 40% had a low level of education, 41% had a medium level, and 19% had a high level; and they reported 1.6 conditions on average (25th75th percentile score interval, zero to two conditions). Mean score results from the SF-36, STAI, and self-rated health EQ-5D questionnaires completed by the attenders to screening and by the nonparticipants are shown in Table 1. Tables 2 and 3 show longitudinal comparisons and statistical testing results. SF-36 scores (screening without biopsy): The comparison of mean SF-36 scores at T1 and T3 to investigate the effects of the initial screening tests indicated significantly better health status at T3 for two of eight scales and for the physical component summary. The actual size of the mean differences was less than 2 points. SF-36 scores (screening procedure with biopsy): The comparison of mean SF36 scores at T1 and T5 to investigate the effects of false-positive result of the initial screening followed by biopsy showed significant improvement for two of eight scales and the physical component summary. The mean differences are somewhat larger. The 95% confidence intervals are wider here because of smaller numbers. Comparison of the scores for self-rated health EQ-5D at T1, T2, and T3 (screening procedure without biopsy) and at T1, T2, T4, and T5 (screening procedure with biopsy) did not reveal any statistically significant differences. Anxiety (screening without biopsy): The mean state anxiety score at T3 was, on average, 2.56 points lower than at T2. However, both mean scores were at or below the age- and sex-adjusted reference score for the Dutch general population (mean score, 34; standard deviation, 11) (15). A similar result was found for the STAI trait scores. Anxiety (screening procedure with biopsy): Differences in state anxiety scores observed at T4 and T5 were statistically significant, with a mean difSF-36 summary scores Physical component summary Mental component summary EQ-5D (score 1000) Self-rated health today 84 (78100) 85 (100100) 81 (62100) 70 (5982) 75 (6590) 88 (88100) 90 (100100) 80 (7292) 51 (4856) 56 (5360) 82 (7590) 34 (2740) 32 (2437) 928 REPORTS 85 (80100) 87 (100100) 83 (72100) 70 (5982) 76 (5690) 89 (88100) 89 (100100) 82 (7692) 52 (4956) 56 (5360) 32 (2437) 31 (2336) 82 (7593) 35 (2643) 32 (2338) 53 (5057) 55 (5360) 32 (2436) 32 (2436) 84 (7595) 79 (6595) 79 (75100) 85 (74100) 65 (5277) 74 (6085) 87 (78100) 85 (100100) 80 (7292) 49 (4455) 55 (5261) 80 (7095) 0.78 to +1.19 0.32 to +3.67 +0.29 to +3.07 0.95 to +1.45 0.32 to +1.91 0.61 to +2.28 2.72 to +0.60 +0.69 to +2.75 +0.11 to +0.91 0.20 to +0.90 0.65 to +0.99 Without biopsy: T3 T1 (n 4 381) With biopsy: T5 T1 (n 4 116) Mean difference score 95% confidence interval Mean difference score 95% confidence interval Without biopsy (n 4 381) With biopsy (n 4 116) T3 T2 3.51 to 1.60 1.80 to 0.35 0.60 to +1.14 T4 T2 0.98 to +2.07 0.07 to +2.25 2.31 to +0.78 T5 T4 5.17 to 2.29 2.14 to 0.33 0.31 to +2.42 ference score of 3.73 points, indicating relief of anxiety after obtaining the message that prostate cancer was not confirmed by biopsy. Only the mean score at T4 was marginally higher than the age- and sex-adjusted reference scores. A more detailed look at the anxiety scores by dividing the attenders into two groups by the 75th percentile of the trait anxiety score observed at T2 showed a level effect; that effect can be illustrated by the results of this analysis in the group of men who underwent screening including a biopsy. Men with trait anxiety scores greater than or equal to 35 had a mean state anxiety score at T2 of 43 (25th75th percentile score interval, 3948), at T4 of 45 (3753), and at T5 of 44 (3253). The men with trait anxiety scores below 35 had a mean state anxiety score of 31 (25th75th percentile score interval, 2636) at T2, of 32 (2437) at T4, and of 28 (2132) at T5. A STAI state anxiety score of more than 2 standard deviations above the average age- and sex-adjusted reference score of 34 (standard deviation, 11), i.e., higher than 56, was observed in five (1%) of the attenders at T2, 11 (3%) at T3, five (3%) at T4, and four (3%) at T5. Six men (1% of 495 men who returned usable response to this item; pooled data from T3 and T5) reported that they had experienced pain during the venous blood sampling for the PSA test, and eight (2%) of 494 men reported physical discomfort during the venous blood sampling for the PSA test. Of 491 men, 181 (37%) reported that they had experienced physical discomfort during the digital rectal examination. Furthermore, 139 (29%) of 487 men reported physical discomfort during the transrectal ultrasound procedure. The latter two tests caused pain in 73 (15%) of 491 men and 49 (10%) of 488 screened individuals. The biopsy procedure was reported 2.10 to +1.07 1.77 to +6.86 +1.01 to +7.38 +0.56 to +5.00 3.44 to +1.83 2.03 to +4.06 3.78 to +3.11 3.06 to +2.31 +0.13 to +1.62 1.45 to +1.25 1.86 to +1.76 to have induced pain in 41 (35%) of 116 men and physical discomfort in 64 (55%) of 116 men. Relevant proportions of the men experienced one or more physical symptoms in the week after prostate biopsy (Table 4). Only small percentages reported that symptoms interfered with daily, social, or sexual activity. Comparison of Attenders and Nonparticipants The usable response rate from the nonparticipants was 47% (n 4 235). They had a mean age of 64.8 years (25th75th percentile score interval, 59.570.0 years); 80% were married; 65% were pensioners; their attained level of education was low in 78%, intermediate in 18%, and high in 4%; and they reported 1.5 conditions on average (25th75th percentile score interval, 02). Nonparticipants were less well educated than attenders. Healthstatus scores of the nonparticipants are shown in Table 1. The SF-36 scores of the nonparticipants were in the same range as age- and sex-adjusted reference scores for the SF-36 from the Dutch general population (Aaronson NK, Muller M, Cohen PD, Essink-Bot ML, Fekkes M, Sander Percentage of total man R, et al.: manuscript submitted for publication). The SF-36 scores observed among the attenders generally indicated a better health status than among the general population. The mean trait anxiety scores were slightly different between attenders and nonparticipants. The mean score of 34 observed among the nonparticipants was not higher than the score presented in the reference tables for Dutch men older than 51 years (15). Despite the fact that the initial screening tests for prostate cancer and, in particular, the prostate biopsy caused physical discomfort in large proportions of the attenders, a relevant impact on generic health status was not found. Even falsepositive results of the initial screening tests followed by prostate biopsy caused little interference at the level of activities despite the frequent occurrence of physical symptoms such as hematuria. Although the nonresponse rate to the T4 questionnaire was low (2%), it may, however, partly be caused by subjects having severe complications, such as septicemia, after biopsy. Rietbergen et al. (18) studied 1687 patients who underwent a prostate biopsy procedure and reported that seven (0.4%) had to be admitted to a hospital after biopsy, with one patient having a life-threatening sepsis. The results do not provide strong support for an anxiety-raising effect of the screening. The mean state anxiety score observed in the subjects in the waiting room before the screening was significantly higher than that observed in the subjects after being informed that the results of the initial tests were unsuspicious. The mean state anxiety score was highest in the men who underwent a prostate biopsy procedure but who were not yet aware of the results from the histologic examination of their specimens. However, the changes in the anxiety scores were small in absolute terms, and the mean scores remained in the range of the age- and sex-adjusted reference scores for the Dutch population. There are at least two possible interpretations for these results. First, prostate cancer screening examinations may be perceived by attenders as routine tests. Separate analyses revealed that men with a high predisposition to anxiety experi*Absolute numbers per item may not add up to 160 because of incidental missing values. ence high anxiety levels throughout the screening process. No information is available as to whether the observed high anxiety scores decrease further in the direction of normal after a longer period after the screening. A second explanation relates to the method of quantitative selfassessment using the STAI. Maybe this approach is too general for measuring anxiety in a screening situation. The results of our study are remarkably similar to those of Sutton et al. (19), which did not show anxiety-raising effects of breast cancer screening. The use of a measure directed specifically at worries related to prostate cancer, similar to the approach advocated by Lerman et al. (20) in breast cancer screening, could provide additional insight. Other approaches could include qualitative or psychophysiologic research. Nonparticipants appeared to differ from the attenders, particularly with respect to educational level. The similarity of the trait anxiety scores among nonparticipants and attenders challenges the hypothesis of psychological self-selection as a cause of nonparticipation. Results from other prostate cancer screening studies for comparison purposes are not available in the literature. Published empirical studies on the healthstatus effects of cancer screening programs remain scarce. There is evidence that the initial screening test (mammography) in breast cancer screening generally does not have important negative psychological consequences (without ignoring the fact that mammography can be quite painful). The recall for additional diagnostic work-up (biopsy) in women whose biopsy specimens later proved to be falsepositives induced substantial distress that lasted beyond receiving reassurance that all was well; however, 6 months later, no excess distress was demonstrated by these women (20,21). The results of our study can be seen as negative. The other interpretation is that we did not find empirical support for one type of objection to population screening programs in general, i.e., the assumption that the availability of a screening program provokes emotional distress among large population groups. If prostate cancer mortality and the incidence of end-stage disease are reduced by early detection programs, unfavorable health-status effects of prostate cancer screening occur mainly in the treatment phase. (1) Schroder FH , Denis LJ , Kirkels W , De Koning HJ , Standaert B. European randomized study of screening for prostate cancer . Progress report of Antwerp and Rotterdam pilot studies. Cancer 1995 ; 76 : 129 - 34 . (2) Auvinen A. Screening for prostate cancer using serum prostate-specific antigen: a randomised, population-based pilot study in Finland . Br J Cancer 1996 ; 74 : 568 - 72 . (3) Kramer BS , Gohagan J , Prorok PC , Smart C. A National Cancer Institute sponsored screening trial for prostatic , lung, colorectal, and ovarian cancers. Cancer 1993 ; 71 : 589 - 93 . (4) Auvinen A , Rietbergen JB , Denis LJ , Schroder FH , Prorok PC . Prospective evaluation plan for randomised trials of prostate cancer screening . The International Prostate Cancer Screening Trial Evaluation Group. J Med Screen 1996 ; 3 : 97 - 104 . (5) Stewart-Brown S , Farmer A. Screening could seriously damage your health [editorial] . BMJ 1997 ; 314 : 533 - 4 . (6) de Koning HJ , van Ineveld BM , de Haes JC , van Oortmarssen GJ , Klijn JG , van der Maas PJ . Advanced breast cancer and its prevention by screening . Br J Cancer 1992 ; 65 : 950 - 5 . (7) de Haes JC , de Koning HJ , van Oortmarssen GJ , van Agt HM , de Bruyn AE , van der Maas PJ . The impact of a breast cancer screening programme on quality-adjusted life-years . Int J Cancer 1991 ; 49 : 538 - 44 . (8) Schroder FH , Damhuis RA , Kirkels WJ , de Koning HJ , Kranse R , Nijs HG , et al. European randomized study of screening for prostate cancer-the Rotterdam pilot studies . Int J Cancer 1996 ; 65 : 145 - 51 . (9) Ware JE , Snow KK , Kosinski M , Gandek B. SF-36 health survey manual and interpretation guide . Boston: New England Medical Center, The Health Institute , 1993 . (10) Ware JE , Kosinski M , Keller SD . SF-36 physical and mental component summary measures-a users' manual . Boston: New England Medical Center, The Health Institute , 1994 . (11) Ware JE Jr, Kosinski M , Bayliss MS , McHorney CA , Rogers WH , Raczek A. Comparison of methods for the scoring and statistical analysis of SF-36 Health Profile and Summary measures: summary of results from the Medical Outcomes Study . Med Care 1995 ; 33 ( 4 Suppl): AS264 - 79 . (12) Aaronson NK , Acquadro C , Alonso J , Apolone G , Bucquet D , Bullinger M , et al. International Quality of Life Assessment (IQOLA) Project. Qual Life Res 1992 ; 1 : 349 - 51 . (13) Brooks RG , EuroQol Group . EuroQol: the current state of play . Health Policy 1996 ; 37 : 53 - 72 . (14) EuroQol Group. EQ-5D user guide . Rotterdam, The Netherlands: EuroQol Business Management , 1996 . (15) van der Ploeg HM , Defares PB , Spielberger CD, editors. Manual of the state-trait anxiety inventory (Handleiding bij de zelfbeoordelingsvragenlijst) (in Dutch) . Leiden, The Netherlands: Swets & Zeitlinger , 1980 . (16) van der Ploeg HM . Validation of the state-trait anxiety inventory (Validatie van de zelfbeoordelingsvragenlijst) (in Dutch) . Ned T Psychol 1980 ; 35 : 243 - 9 . (17) Spielberger CD , Gorschuch RL , Lushene RE, editors. STAI manual for the state-trait anxiety inventory . Palo Alto (CA): Consulting Psychologists Press, 1970 . (18) Rietbergen JB , Kruger AE , Kranse R , Schroder FH . Complications of transrectal ultrasoundguided systematic sextant biopsies of the prostate: evaluation of complication rates and risk factors within a population-based screening program . Urology 1997 ; 49 : 875 - 80 . (19) Sutton S , Saidi G , Bickler G , Hunter H. Does routine screening for breast cancer raise anxiety? Results from a three wave prospective study in England . J Epidemiol Community Health 1995 ; 49 : 413 - 8 . (20) Lerman C , Trock B , Rimer BK , Jepson C , Brody D , Boyce A. Psychological side effects of breast cancer screening . Health Psychol 1991 ; 10 : 259 - 67 . (21) Cockburn J , Staples M , Hurley SF , De Luise T. Psychological consequences of screening mammography . J Med Screen 1994 ; 1 : 7 - 12 .


This is a preview of a remote PDF: https://jnci.oxfordjournals.org/content/90/12/925.full.pdf

Marie-Louise Essink-Bot, Harry J. de Koning, Hubert G. T. Nijs, Wim J. Kirkels, Paul J. van der Maas, Fritz H. Schröder. Short-Term Effects of Population-Based Screening for Prostate Cancer on Health-Related Quality of Life, JNCI Journal of the National Cancer Institute, 1998, 925-931, DOI: 10.1093/jnci/90.12.925