Health Technology Assessment 2003; Vol. 7: No. 14
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and the ProtecT Study Group: J Anderson, M Benney, S Burton, I Emmerson, J Goepel, L Goodwin, J Graham, D Gunnell, H Harris, B Hattrick, P Holding, C Kennedy, S Kilner, P Kirkbride, H Leung, T Mewes, J Oxley, I Pedley, M Robinson, L Salter, M Sidaway, C Torrington, L Wilkinson, A Wilson
Department of Social Medicine, University of Bristol, UK
* Corresponding author
There is currently insufficient evidence to introduce population screening for prostate cancer. While it is accepted that prostate cancer is an important public health problem, there is paucity of evidence on the natural history of the disease, the accuracy of diagnostic tests (e.g. prostate-specific antigen (PSA) testing) and the effectiveness of treatments.
The overall aim was to evaluate the feasibility of a randomised controlled trial (RCT) of treatments for localised prostate cancer, including:
The study was an RCT of treatment preceded by case-finding in the community, with qualitative research methods integrated at each stage. Case-finding took place in primary care centres in Sheffield, Newcastle and Bristol. The RCT was undertaken in urology clinics in these same centres. Men aged 5069 years from specific primary care centres in the three cities were invited to attend a 30-minute prostate check clinic appointment in which they were informed about the study and asked to consent to a PSA test. Men with a raised PSA (initially > 3.0 ng/ml if 5059 years; > 4.0 ng/ml if 6069 years; but changed to > 3.0 ng/ml for all men after 1 year) were invited for biopsy. Men with confirmed localised prostate cancer were invited to participate in a randomised trial of recruitment strategies.
Men with confirmed localised prostate cancer were asked to consent to randomisation between a nurse or urologist for an ‘information’ appointment to discuss recruitment to the treatment trial. In the information appointment, the need for a trial was explained in detail, along with the advantages and disadvantages of each treatment, and the recruiter attempted to randomise the patient to the treatment trial or reach a patient-led preference for a treatment. All men, whether randomised or not, were asked to consent to be followed-up, and these formed a pilot for the proposed main trial.
Numbers of men agreeing to attend prostate check clinics and then going on to have a PSA test, biopsy and diagnosis of prostate cancer were calculated. The accuracy of PSA testing was calculated by positive predictive values (PPVs) at various cut-points. The psychosocial impact of case-finding was investigated through the use of the Hospital Anxiety and Depression Scale (HADS) and ICSmale (urinary symptoms) questionnaire, completed by all men at baseline and those with raised PSA levels at the time of biopsy.
The primary outcome was the proportion of patients accepting randomisation to the treatment trial. Also calculated were the proportions consenting to randomisation to the three- (radical prostatectomy, radical radiotherapy and ‘conservative’ management) or two-arm (radical options only) trial and those accepting the random allocation. An economic analysis based on the duration of information appointments and recruiter salaries was performed to assess the most cost-effective recruiting staff.
In-depth interviews were undertaken with several groups:
In addition, tape-recorded information appointments were examined. Changes to information content and presentation were made and the proportions consenting to be randomised to the treatment trial and accepting the allocation were calculated regularly to examine the impact of these changes.
All men with confirmed localised prostate cancer completed a baseline study questionnaire at the time of case-finding and biopsy. A further questionnaire was completed 6 months after the information appointment, with the major research follow-up to be at 12 months and annually thereafter in the main trial.
A total of 8505 men from 18 primary care centres attended prostate check clinics (56% of those invited), and 7383 had a PSA test. Of these, 861 (12%) had raised PSA levels, and following biopsy, 224 cases of prostate cancer were found (165 clinically localised). The detection rate was 2.2% of clinic attendees. PPVs confirmed that a PSA cut-point of 3 ng/ml was suitable. At the time of PSA testing, levels of depression were low (3.2% ‘cases’) and anxiety somewhat higher (11.6% ‘cases’), but these remained virtually unchanged among those completing questionnaires at the time of biopsy.
Ninety per cent of eligible cases consented to randomisation between a nurse and urologist. Urologists achieved a higher rate of recruitment to the treatment trial (71% compared with 67% for nurses), but this was not statistically significant (p = 0.60). As effectiveness was essentially the same between the two arms, a cost-minimisation analysis was performed and showed that the urologist arm was more expensive because greater salary costs outweighed their tendency for shorter appointments and nurses often supported surgeon-led clinics.
The three-arm trial was the most popular treatment trial option, with 84% opting for this rather than the two-arm trial (p < 0.001). The acceptance of the treatment allocation was 71% within the three-arm trial.
The offer of PSA testing was construed as an opportunity to discover an unknown condition and the majority of men indicated that they understood that the study involved investigation of treatments. While the majority could recall clearly the principles of randomisation, issues around clinical equipoise caused many considerable difficulty. Recruitment to the treatment trial increased gradually during the feasibility study, from 3040% at the outset to 70% by the end of the feasibility study. These improvements in recruitment were brought about by changes to the content and presentation of information, particularly avoidance of terms such as ‘trial’ and ‘watchful waiting’, and the clear specification of the non-radical treatment arm, as directed by the findings of the qualitative research.
Donovan J, Hamdy F, Neal D, Peters T, Oliver S, Brindle L, et al. Prostate Testing for Cancer and Treatment (ProtecT) feasibility study. Health Technol Assess 2003;7(14).
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The research reported in this monograph was funded as project number 96/20/06.
The views expressed in this publication are those of the authors and not necessarily those of the HTA Programme or the Department of Health. The editors wish to emphasize that funding and publication of this research by the NHS should not be taken as implicit support for the recommendations for policy contained herein. In particular, policy options in the area of screening will be considered by the National Screening Committee. This Committee, chaired by the Chief Medical Officer, will take into account the views expressed here, further available evidence and other relevant considerations.
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