General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms cancer was higher in the intervention (4.3%) group than control (3.6%) group, but there was no significant difference in prostate cancer mortality (intervention, 0.29% vs. control, 0.29%) after a median follow-up of 10-years. Meaning:The CAP single PSA-screen intervention detected more prostate cancer cases, but after a median of 10-years' follow-up has, thus far, had no significant effect on prostate cancer mortality. Conclusion and relevance:Among practices randomized to a low-intensity PSA screening intervention compared with standard practice, there was no significant difference in prostate cancer mortality after a 4 median 10-years follow up, but the detection of low-risk prostate cancers increased. Although longer-term follow-up is in progress, the current findings do not support single PSA-testing for population-based screening.

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Study Type – Practice patterns (retrospective cohort) Level of Evidence 2b What is known on the subject? and what does the study add? There is no organized screening programme for prostate cancer in the UK, although men can request a PSA test at their general practice. The testing rate had been estimated at 6% per year among 45–84 year old men during 2001 to 2007. Our study estimated the annual practice‐based PSA testing rate for men aged 45–89 years with no previous diagnosis of prostate cancer at 6.2% during 2007. This is very similar to the rate found in the earlier study. Older men and men at general practices situated in more affluent areas were found to be most likely to undergo a PSA test, suggesting that uptake of the test is not reflecting clinical need. OBJECTIVE • To estimate rates of prostate‐specific antigen (PSA) testing in UK general practices by age, deprivation index and geographical location. SUBJECTS AND METHODS • Practice‐based, retrospective data on PSA testing patterns in 2007 were collected from a random sample of 87 general practices using EMIS LV computer systems within the passively observed non‐intervention arm of a cluster‐randomized controlled trial. • Information for a total of 126 716 men aged 45–89 years with no recorded diagnosis of prostate cancer prior to 1 January 2007 was collected. RESULTS • In all, 7902 (6.2%) of 126 716 men aged 45–89 without a prior diagnosis of prostate cancer underwent at least one PSA test from their general practitioner during 2007 [95% confidence interval (CI) 5.6–7.0%; practice‐based inter‐quartile range 3.6–8.4%]. • PSA testing rates were 1.4% (95% CI 1.1–1.6%) in men aged 45–49, rising to 11.3% (95% CI 10.0–12.9%) at age 75–79 years (P for trend <0.001). • Testing rates were lowest in the three northern centres (3.5–5.7%) vs the three more southern centres (7.1–8.9%; P < 0.001). • For every 20 points increase in the index of multiple deprivation score, the proportion of men tested fell by 1.7% (95% CI −2.5 to −0.8%; P < 0.001). • Lower proportions of men were subsequently diagnosed with prostate cancer in practices testing more men (odds ratio for a one unit increase in the natural log of testing 0.76; 95% CI 0.60–0.97; P= 0.025). CONCLUSION • Overall levels of PSA testing in UK general practice remain low, but for those tested there are important variations by age, deprivation and geographical location that do not appear to reflect clinical need or the intention of current policy. • PSA testing in general practice is currently skewed towards older men, and current policy enabling all men to make an informed choice about PSA testing is not being effectively implemented as uptake clearly varies by socioeconomic status. • This reinforces the need for robust evidence regarding the costs and benefits of using the PSA test for the detection of localized prostate cancer in the UK, a full assessment of the health economic implications and a revision of the current policy.

Summary Background Whole-body magnetic resonance imaging (WB-MRI) could be an alternative to multi-modality staging of non-small-cell lung cancer (NSCLC), but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in NSCLC. Methods The Streamline L trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed NSCLC that was potentially radically treatable on diagnostic chest CT (defined as stage IIIb or less). Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or histologies other than NSCLC. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs) and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN50436483, and is complete. Findings Between Feb 26, 2013, and Sept 5, 2016, 976 patients were screened for eligibility. 353 patients were recruited, 187 of whom completed the trial; 52 (28%) had metastasis at baseline. Pathway sensitivity was 50% (95% CI 37–63) for WB-MRI and 54% (41–67) for standard pathways, a difference of 4% (−7 to 15, p=0·73). No adverse events related to imaging were reported. Specificity did not differ between WB-MRI (93% [88–96]) and standard pathways (95% [91–98], p=0·45). Agreement with the multidisciplinary team's final treatment decision was 98% for WB-MRI and 99% for the standard pathway. Time to complete staging was shorter for WB-MRI (13 days [12–14]) than for the standard pathway (19 days [17–21]); a 6-day (4–8) difference. The number of tests required was similar WB-MRI (one [1–1]) and standard pathways (one [1–2]). Mean per-patient costs were £317 (273–361) for WBI-MRI and £620 (574–666) for standard pathways. Interpretation WB-MRI staging pathways have similar accuracy to standard pathways, and reduce the staging time and costs. Funding UK National Institute...

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.

Background Whole-body MRI (WB-MRI) could be an alternative to multimodality staging of colorectal cancer, but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in colorectal cancer. Methods The Streamline C trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed colorectal cancer. Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or polyp cancer. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs), and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN43958015, and is complete.

PurposeTo report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer.Patients and MethodsPatients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined.ResultsEight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years.ConclusionsIDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.