Modelling the lifetime cost-effectiveness of radical prostatectomy, radiotherapy and active monitoring for men with clinically localised prostate cancer from median 10-year outcomes in the ProtecT randomised trial.

BACKGROUND: Optimal management strategies for clinically localised prostate cancer are debated. Using median 10-year data from the largest randomised controlled trial to date (ProtecT), the lifetime cost-effectiveness of three major treatments (radical radiotherapy, radical prostatectomy and active monitoring) was explored according to age and risk subgroups. METHODS: A decision-analytic (Markov) model was developed and informed by clinical input. The economic evaluation adopted a UK NHS perspective and the outcome was cost per Quality-Adjusted Life Year (QALY) gained (reported in UK£), estimated using EQ-5D-3L. RESULTS: Costs and QALYs extrapolated over the lifetime were mostly similar between the three randomised strategies and their subgroups, but with some important differences. Across all analyses, active monitoring was associated with higher costs, probably associated with higher rates of metastatic disease and changes to radical treatments. When comparing the value of the strategies (QALY gains and costs) in monetary terms, for both low-risk prostate cancer subgroups, radiotherapy generated the greatest net monetary benefit (£293,446 [95% CI £282,811 to £299,451] by D'Amico and £292,736 [95% CI £284,074 to £297,719] by Grade group 1). However, the sensitivity analysis highlighted uncertainty in the finding when stratified by Grade group, as radiotherapy had 53% probability of cost-effectiveness and prostatectomy had 43%. In intermediate/high risk groups, using D'Amico and Grade group > = 2, prostatectomy generated the greatest net monetary benefit (£275,977 [95% CI £258,630 to £285,474] by D'Amico and £271,933 [95% CI £237,864 to £287,784] by Grade group). This finding was supported by the sensitivity analysis. Prostatectomy had the greatest net benefit (£290,487 [95% CI £280,781 to £296,281]) for men younger than 65 and radical radiotherapy (£201,311 [95% CI £195,161 to £205,049]) for men older than 65, but sensitivity analysis showed considerable uncertainty in both findings. CONCLUSION: Over the lifetime, extrapolating from the ProtecT trial, radical radiotherapy and prostatectomy appeared to be cost-effective for low risk prostate cancer, and radical prostatectomy for intermediate/high risk prostate cancer, but there was uncertainty in some estimates. Longer ProtecT trial follow-up is required to reduce uncertainty in the model. TRIAL REGISTRATION: Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.

BACKGROUND: Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. METHODS: We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. RESULTS: The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life. CONCLUSIONS: In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM) for diagnosis and management of bladder outlet obstruction in men: study protocol for a randomised controlled trial.

BACKGROUND: Lower urinary tract symptoms (LUTS) comprise storage symptoms, voiding symptoms and post-voiding symptoms. Prevalence and severity of LUTS increase with age and the progressive increase in the aged population group has emphasised the importance to our society of appropriate and effective management of male LUTS. Identification of causal mechanisms is needed to optimise treatment and uroflowmetry is the simplest non-invasive test of voiding function. Invasive urodynamics can evaluate storage function and voiding function; however, there is currently insufficient evidence to support urodynamics becoming part of routine practice in the clinical evaluation of male LUTS. DESIGN: A 2-arm trial, set in urology departments of at least 26 National Health Service (NHS) hospitals in the United Kingdom (UK), randomising men with bothersome LUTS for whom surgeons would consider offering surgery, between a care pathway based on urodynamic tests with invasive multichannel cystometry and a care pathway based on non-invasive routine tests. The aim of the trial is to determine whether a care pathway not including invasive urodynamics is no worse for men in terms of symptom outcome than one in which it is included, at 18 months after randomisation. This primary clinical outcome will be measured with the International Prostate Symptom Score (IPSS). We will also establish whether inclusion of invasive urodynamics reduces rates of bladder outlet surgery as a main secondary outcome. DISCUSSION: The general population has an increased life-expectancy and, as men get older, their prostates enlarge and potentially cause benign prostatic obstruction (BPO) which often requires surgery. Furthermore, voiding symptoms become increasingly prevalent, some of which may not be due to BPO. Therefore, as the population ages, more operations will be considered to relieve BPO, some of which may not actually be appropriate. Hence, there is sustained interest in the diagnostic pathway and this trial could improve the chances of an accurate diagnosis and reduce overall numbers of surgical interventions for BPO in the NHS. The morbidity, and therapy costs, of testing must be weighed against the cost saving of surgery reduction. TRIAL REGISTRATION: Controlled-trials.com - ISRCTN56164274 (confirmed registration: 8 April 2014).

Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

BACKGROUND: Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. METHODS: Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50-69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up. RESULTS: Among randomised practices, 271 (68%) in the intervention arm (198,114 men) and 302 (78%) in the control arm (221,929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices). CONCLUSIONS: The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening.

Clinical trial: prolonged beneficial effect of Helicobacter pylori eradication on dyspepsia consultations - the Bristol Helicobacter Project.

BACKGROUND: Chronic infection of the stomach with Helicobacter pylori is widespread throughout the world and is the major cause of peptic ulcer disease and gastric cancer. Short-term benefit results from community programmes to eradicate the infection, but there is little information on cumulative long-term benefit. AIM: To determine whether a community programme of screening for and eradication of H. pylori infection produces further benefit after an initial 2-year period, as judged by a reduction in GP consultations for dyspepsia. METHODS: A total of 1517 people aged 20-59 years, who were registered with seven general practices in Frenchay Health District, Bristol, had a positive (13)C-urea breath test for H. pylori infection and were entered into a randomized double-blind trial of H. pylori eradication therapy. After 2 years, we found a 35% reduction in GP consultations for dyspepsia (previously reported). In this extension to the study, we analysed dyspepsia consultations between two and 7 years after treatment. RESULTS: Between two and 7 years after treatment, 81/764 (10.6%) of participants randomized to receive active treatment consulted for dyspepsia, compared with 106/753 (14.1%) of those who received placebo, a 25% reduction, odds ratio 0.84 (0.71, 1.00), P = 0.042. CONCLUSIONS: Eradication of H. pylori infection in the community gives cumulative long-term benefit, with a continued reduction in the development of dyspepsia severe enough to require a consultation with a general practitioner up to at least 7 years. The cost savings resulting from this aspect of a community H. pylori eradication programme, in addition to the other theoretical benefits, make such programmes worthy of serious consideration, particularly in populations with a high prevalence of H. pylori infection.

Assessment of the tear film with tandem scanning confocal microscopy.

PURPOSE: To evaluate the confocal microscopic appearance of the tear film by correlating the interference pattern created by the lipid surface with physiologic measurements of tear function and with clinic diagnosis. METHODS: A series of 53 patients was examined with a battery of tests to evaluate the tear film and with confocal microscopy to evaluate the interference pattern created by the lipid surface of the tear film. Assessment of the tear-film appearance involved five nonparametric scales: degree of debris in the tear film, variability of the interference pattern over time, linearity of the interference pattern, number of dry spots seen, and relative thickness of the lipid layer. For 10 other subjects, the confocal appearance of the tear film and evaporation from the ocular surface was tested for before and after meibomian gland expression. RESULTS: The confocal appearance correlated with multiple physiologic variables and clinical diagnosis. Patients with seborrheic meiboman gland dysfunction had a thicker lipid layer, greater variability, and more debris than did patients with obstructive meibomiam gland dysfunction. After meibomian gland expression, lipid thickness and linearity increased, whereas pattern variability and evaporation decreased significantly. The mean reduction in evaporation was 48%. CONCLUSIONS: Confocal microscopy can be used to examine the tear film, and its appearance correlates significantly with physiologic variables in normal-individuals and in disease states. The confocal appearance of the lipid interference patterns and evaporation from the ocular surface are altered after lipid expression from meibomian glands.