Risk of mature B-cell neoplasms and precursor conditions after joint replacement: A report from the Haematological Malignancy Research Network.

Associations between previous joint replacement and B-cell lymphoid malignancies have been reported, but despite numerous reports, associations with the disease subtypes have received little attention. Using a UK-based register of haematological malignancies and a matched general population-based cohort, joint replacements from linked hospital inpatient records were examined. Cases diagnosed 2009-2015 who were aged 50 years or more were included; 8,013 mature B-cell neoplasms comprising myeloma (n = 1,763), diffuse large B-cell lymphoma (DLBCL, n = 1,676), chronic lymphocytic leukaemia (CLL, n = 1,594), marginal zone lymphoma (MZL, n = 957), follicular lymphoma (FL, n = 725) and classical Hodgkin lymphoma (CHL, n = 255), together with monoclonal gammopathy of uncertain significance (MGUS, n = 2,138) and monoclonal B-cell lymphocytosis (MBL, n = 632). Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated relative to 10 age- and sex-matched controls using conditional logistic regression. Having had a joint replacement before diagnosis was associated with myeloma (OR = 1.3, 95% CI 1.1-1.5, p = 0.008) and MGUS (OR = 1.3, 95% CI 1.1-1.5, p < 0.001). Excluding replacements in the year before diagnosis, the MGUS risk remained, elevated where two or more joints were replaced (OR = 1.5, 95% CI 1.2-2.0, p = 0.001), with hip (OR = 1.2, 95% CI 1.0-1.5, p = 0.06) or knee replacements (OR = 1.5, 95% CI 1.2-1.8, p < 0.001). Associations with CHL and two or more replacements (OR = 2.7, 95% CI 1.3-5.6, p = 0.005) or hip replacements (OR = 1.9, 95% CI 1.0-3.4, p = 0.04); and between DLBCL and knee replacements (OR = 1.3, 95% CI 1.0-1.6, p = 0.04) were also observed. Our study reports for the first time a relationship between joint replacements and MGUS; while absolute risks of disease are low and not of major public health concern, these findings warrant further investigation.

Patient non-attendance at urgent referral appointments for suspected cancer and its links to cancer diagnosis and one year mortality: A cohort study of patients referred on the Two Week Wait pathway.

BACKGROUND: The 'Two Week Wait' policy aims to ensure patients with suspected cancer are seen within two weeks of referral. However, patient non-attendance can result in this target being missed. This study aimed to identify predictors of non-attendance; and analyse the relationship between attendance and outcomes including cancer diagnosis and early mortality. METHODS: A cohort study of 109,433 adults registered at 105 general practices, referred to a cancer centre within a large NHS hospital trust (April 2009 to December 2016) on the 'Two Week Wait' pathway. RESULTS: 5673 (5.2%) patients did not attend. Non-attendance was largely predicted by patient factors (younger and older age, male gender, greater deprivation, suspected cancer site, earlier year of referral, greater distance to the hospital) over practice factors (greater deprivation, lower Quality and Outcomes Framework score, lower cancer conversion rate, lower cancer detection rate). 10,360 (9.6%) patients were diagnosed with cancer within six months of referral (9.8% attending patients, 5.6% non-attending patients). Among these patients, 2029 (19.6%) died within 12 months of diagnosis: early mortality risk was 31.3% in non-attenders and 19.2% in attending patients. CONCLUSIONS: Non-attendance at urgent referral appointments for suspected cancer involves a minority of patients but happens in predictable groups. Cancer diagnosis was less likely in non-attending patients but these patients had worse early mortality outcomes than attending patients. The study findings have implications for cancer services and policy.

The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 in a pooled analysis of 16,024 men from 22 studies.

Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.

Time intervals from first symptom to diagnosis for head and neck cancers: An analysis of linked patient reports and medical records from the UK.

BACKGROUND: England has significantly higher mortality risks due to Head and Neck Cancer (HNC) compared with other European countries. Early diagnosis is important as it is likely to increase early-stage diagnosis and improve survival and better quality of life. This study sought to improve understanding of the intervals from first symptom recognition to diagnosis for HNC and investigate associations between patient-reported symptoms and socio-demographic factors. METHODS: People within 3 months of diagnosis, completed a researcher-administered questionnaire and data were extracted from primary and secondary care clinical records. RESULTS: Eighty (mean age 62.9 [SD 11.7] years; 66% men) were interviewed. The appraisal interval was longer than a month for 39% of participants and the help-seeking interval was longer than a week for 44%. The median diagnostic interval was 92 (IQR; 34-172) days. Appraisal intervals of > 1 month were associated with male gender, ulceration and persistent throat pain. The only symptom that associated with a help-seeking interval of > 1 week was ulceration. Participants who reported red/white patches in the mouth and ulceration were associated with a reduced likelihood of a diagnostic interval of > 3 months. A higher proportion of participants with a diagnostic interval of > 3 months were diagnosed with advanced disease (78%) than those with an interval < 3 months (68%). CONCLUSION: These data improve understanding of the intervals from first symptom recognition to HNC diagnosis and provide preliminary evidence to identify targets to reduce overall time to diagnosis.

Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer Mortality: The CAP Randomized Clinical Trial.

Importance: Prostate cancer screening remains controversial because potential mortality or quality-of-life benefits may be outweighed by harms from overdetection and overtreatment. Objective: To evaluate the effect of a single prostate-specific antigen (PSA) screening intervention and standardized diagnostic pathway on prostate cancer-specific mortality. Design, Setting, and Participants: The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) included 419 582 men aged 50 to 69 years and was conducted at 573 primary care practices across the United Kingdom. Randomization and recruitment of the practices occurred between 2001 and 2009; patient follow-up ended on March 31, 2016. Intervention: An invitation to attend a PSA testing clinic and receive a single PSA test vs standard (unscreened) practice. Main Outcomes and Measures: Primary outcome: prostate cancer-specific mortality at a median follow-up of 10 years. Prespecified secondary outcomes: diagnostic cancer stage and Gleason grade (range, 2-10; higher scores indicate a poorer prognosis) of prostate cancers identified, all-cause mortality, and an instrumental variable analysis estimating the causal effect of attending the PSA screening clinic. Results: Among 415 357 randomized men (mean [SD] age, 59.0 [5.6] years), 189 386 in the intervention group and 219 439 in the control group were included in the analysis (n = 408 825; 98%). In the intervention group, 75 707 (40%) attended the PSA testing clinic and 67 313 (36%) underwent PSA testing. Of 64 436 with a valid PSA test result, 6857 (11%) had a PSA level between 3 ng/mL and 19.9 ng/mL, of whom 5850 (85%) had a prostate biopsy. After a median follow-up of 10 years, 549 (0.30 per 1000 person-years) died of prostate cancer in the intervention group vs 647 (0.31 per 1000 person-years) in the control group (rate difference, -0.013 per 1000 person-years [95% CI, -0.047 to 0.022]; rate ratio [RR], 0.96 [95% CI, 0.85 to 1.08]; P = .50). The number diagnosed with prostate cancer was higher in the intervention group (n = 8054; 4.3%) than in the control group (n = 7853; 3.6%) (RR, 1.19 [95% CI, 1.14 to 1.25]; P < .001). More prostate cancer tumors with a Gleason grade of 6 or lower were identified in the intervention group (n = 3263/189 386 [1.7%]) than in the control group (n = 2440/219 439 [1.1%]) (difference per 1000 men, 6.11 [95% CI, 5.38 to 6.84]; P < .001). In the analysis of all-cause mortality, there were 25 459 deaths in the intervention group vs 28 306 deaths in the control group (RR, 0.99 [95% CI, 0.94 to 1.03]; P = .49). In the instrumental variable analysis for prostate cancer mortality, the adherence-adjusted causal RR was 0.93 (95% CI, 0.67 to 1.29; P = .66). Conclusions and Relevance: Among practices randomized to a single PSA screening intervention vs standard practice without screening, there was no significant difference in prostate cancer mortality after a median follow-up of 10 years but the detection of low-risk prostate cancer cases increased. Although longer-term follow-up is under way, the findings do not support single PSA testing for population-based screening. Trial Registration: ISRCTN Identifier: ISRCTN92187251.

Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men.

INTRODUCTION: Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin. METHODS: Statistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates. RESULTS: Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones. CONCLUSION: Circulating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.

Prostate-specific antigen (PSA) testing of men in UK general practice: a 10-year longitudinal cohort study.

OBJECTIVES: Cross-sectional studies suggest that around 6% of men undergo prostate-specific antigen (PSA) testing each year in UK general practice (GP). This longitudinal study aims to determine the cumulative testing pattern of men over a 10-year period and whether this testing can be considered equivalent to screening for prostate cancer (PCa). SETTING, PARTICIPANTS AND OUTCOME MEASURES: Patient-level data on PSA tests, biopsies and PCa diagnoses were obtained from the UK Clinical Practice Research Datalink (CPRD) for the years 2002 to 2011. The cumulative risks of PSA testing and of being diagnosed with PCa were estimated for the 10-year study period. Associations of a man's age, region and index of multiple deprivation with the cumulative risk of PSA testing and PCa diagnosis were investigated. Rates of biopsy and diagnosis, following a high test result, were compared with those from the programme of PSA testing in the Prostate Testing for Cancer and Treatment (ProtecT) study. RESULTS: The 10-year risk of exposure to at least one PSA test in men aged 45 to 69 years in UK GP was 39.2% (95% CI 39.0 to 39.4%). The age-specific risks ranged from 25.2% for men aged 45-49 years to 53.0% for men aged 65-69 years (p for trend <0.001). For those with a PSA level ≥3, a test in UK GP was less likely to result in a biopsy (6%) and/or diagnosis of PCa (15%) compared with ProtecT study participants (85% and 34%, respectively). CONCLUSION: A high proportion of men aged 45-69 years undergo PSA tests in UK GP: 39% over a 10-year period. A high proportion of these tests appear to be for the investigation of lower urinary tract symptoms and not screening for PCa. TRIAL REGISTRATION NUMBER: ISRCTN20141297,NCT02044172.

Contemporary accuracy of death certificates for coding prostate cancer as a cause of death: Is reliance on death certification good enough? A comparison with blinded review by an independent cause of death evaluation committee.

BACKGROUND: Accurate cause of death assignment is crucial for prostate cancer epidemiology and trials reporting prostate cancer-specific mortality outcomes. METHODS: We compared death certificate information with independent cause of death evaluation by an expert committee within a prostate cancer trial (2002-2015). RESULTS: Of 1236 deaths assessed, expert committee evaluation attributed 523 (42%) to prostate cancer, agreeing with death certificate cause of death in 1134 cases (92%, 95% CI: 90%, 93%). The sensitivity of death certificates in identifying prostate cancer deaths as classified by the committee was 91% (95% CI: 89%, 94%); specificity was 92% (95% CI: 90%, 94%). Sensitivity and specificity were lower where death occurred within 1 year of diagnosis, and where there was another primary cancer diagnosis. CONCLUSIONS: UK death certificates accurately identify cause of death in men with prostate cancer, supporting their use in routine statistics. Possible differential misattribution by trial arm supports independent evaluation in randomised trials.

Variation in incidence and survival by ethnicity for patients with myeloma in England (2002-2008).

Incidence and relative survival of myeloma by ethnic group was estimated using data from cancer registries in England (2002-2008). Multiple imputation was used to address missing ethnicity data. In total 24 361 cases of myeloma were identified. Age-standardized incidence rate (ASIR) (per 100 000) was higher in the Black ethnic category at 15.00 (95% confidence interval [CI] 13.50-16.40), than amongst South Asians (ASIR = 5.45, 95% CI 4.76-6.14) or the White group (ASIR = 6.11, 95% CI 6.00-6.22). There was a lower risk of death in the Black group for both 1- and 3-year survival (hazard ratio [HR]1 year = 0.66, 95% CI 0.55-0.79; HR3 year = 0.69, 95% CI 0.58-0.83) and South Asians at 1, 3 and 5 years (HR1 year = 0.65, 95% CI 0.51-0.82; HR3 year = 0.72, 95% CI I 0.57-0.90; HR5 year = 0.68, 95% CI 0.50-0.92) when compared to the White population. Further study of differences in myeloma and precursor biology between population groups is important.

Life course sun exposure and risk of prostate cancer: population-based nested case-control study and meta-analysis.

There is currently no means of primary prevention for prostate cancer. Increased exposure to ultraviolet-radiation may be protective, but the literature is inconclusive. We investigated associations of life course exposure to sunlight with prostate cancer. The study design was a UK-wide nested case-control study, based on 1,020 prostate specific antigen-detected cases and 5,044 matched population controls and a systematic review with meta-analysis. Men with olive/brown skin (OR = 1.47; 95% CI: 1.00 to 2.17), men who burnt rarely/never (OR = 1.11; 0.95 to 1.29) and men with the lowest levels of intense sun exposure in the 2 years prior to diagnosis (OR = 1.24; 1.03 to 1.50) had an increased prostate cancer risk. However, amongst men with prostate cancer, spending less time outside was associated with a reduced risk of advanced cancer (OR = 0.49; 0.27 to 0.89) and high Gleason grade (OR = 0.62; 0.43 to 0.91), and men who burnt rarely/never had a reduced risk of advanced cancer (OR = 0.71; 0.47 to 1.08). The meta-analysis provided weak evidence that men with the lowest (versus highest) sunlight exposure had an increased prostate cancer risk (4 studies, random-effects pooled relative risk = 1.13; 0.98 to 1.29) and higher advanced or fatal prostate cancer risk (6 studies, random-effects pooled relative risk = 1.14; 0.98 to 1.33). Our data and meta-analyses provide limited support for the hypothesis that increased exposure to sunlight may reduce prostate cancer risk. The findings warrant further investigation because of their implications for vitamin D chemoprevention trials.

Insulin-like growth factors, their binding proteins, and prostate cancer risk: analysis of individual patient data from 12 prospective studies.

BACKGROUND: Some, but not all, published results have shown an association between circulating blood levels of some insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) and the subsequent risk for prostate cancer. PURPOSE: To assess the association between levels of IGFs and IGFBPs and the subsequent risk for prostate cancer. DATA SOURCES: Studies identified in PubMed, Web of Science, and CancerLit. STUDY SELECTION: The principal investigators of all studies that published data on circulating concentrations of sex steroids, IGFs, or IGFBPs and prostate cancer risk using prospectively collected blood samples were invited to collaborate. DATA EXTRACTION: Investigators provided individual participant data on circulating concentrations of IGF-I, IGF-II, IGFBP-II, and IGFBP-III and participant characteristics to a central data set in Oxford, United Kingdom. DATA SYNTHESIS: The study included data on 3700 men with prostate cancer and 5200 control participants. On average, case patients were 61.5 years of age at blood collection and received a diagnosis of prostate cancer 5 years after blood collection. The greater the serum IGF-I concentration, the greater the subsequent risk for prostate cancer (odds ratio [OR] in the highest vs. lowest quintile, 1.38 [95% CI, 1.19 to 1.60]; P < 0.001 for trend). Neither IGF-II nor IGFBP-II concentrations were associated with prostate cancer risk, but statistical power was limited. Insulin-like growth factor I and IGFBP-III were correlated (r = 0.58), and although IGFBP-III concentration seemed to be associated with prostate cancer risk, this was secondary to its association with IGF-I levels. Insulin-like growth factor I concentrations seemed to be more positively associated with low-grade than high-grade disease; otherwise, the association between IGFs and IGFBPs and prostate cancer risk had no statistically significant heterogeneity related to stage or grade of disease, time between blood collection and diagnosis, age and year of diagnosis, prostate-specific antigen level at recruitment, body mass index, smoking, or alcohol intake. LIMITATIONS: Insulin-like growth factor concentrations were measured in only 1 sample for each participant, and the laboratory methods to measure IGFs differed in each study. Not all patients had disease stage or grade information, and the diagnosis of prostate cancer may differ among the studies. CONCLUSION: High circulating IGF-I concentrations are associated with a moderately increased risk for prostate cancer.

Measuring the psychosocial impact of population-based prostate-specific antigen testing for prostate cancer in the UK.

OBJECTIVE: To evaluate the psychosocial impact of participation in a population-based prostate-specific antigen (PSA) testing programme, akin to screening, and to explore the relationship between urinary symptoms reported before PSA testing and the response to the subsequent PSA result. PATIENTS AND METHODS: This prospective questionnaire study was nested within the case-finding component of the ProtecT (prostate testing for cancer and treatment) feasibility study (ISRCTN20141297). Men aged 50-69 years from 18 general practices in three cities in the UK completed the Hospital Anxiety and Depression Scale (HADS), the Short Form-12 (SF-12) Health Survey, and the International Continence Society 'male' (ICSmale) questionnaires before giving consent for a PSA test in a community clinic (baseline). Men with an 'abnormal' PSA result returned for further investigation (including biopsy) and repeated these questionnaires before biopsy. RESULTS: At baseline, study participants had similar levels of anxiety and depression to the general male population. There was no increase in the HADS scores, or reduction in the SF-12 mental health component summary score, on attendance at the biopsy clinic after receiving an 'abnormal' PSA result. Urinary symptoms were associated with levels of anxiety and depression before receiving a PSA result (baseline), but were not associated with anxiety and depression at biopsy independently of baseline scores. Therefore changes in anxiety or depression at biopsy did not appear to differ between those with and without urinary symptoms. CONCLUSIONS: This study confirms the findings of other studies that the deleterious effects of receiving an abnormal PSA result during population screening are not identified by generic health-status questionnaires. Comparisons with outcomes of studies measuring cancer-specific distress and using qualitative research methods raise the question of whether a prostate cancer screening-specific instrument is required. However, a standardized measure of anxiety identified differences at baseline between those who did and did not report urinary symptoms. These findings suggest that it might be advisable to better inform men undergoing PSA testing about the uncertain relationship between urinary symptoms and prostate cancer, to minimize baseline levels of psychological distress.

Measurement of insulin-like growth factor axis does not enhance specificity of PSA-based prostate cancer screening.

OBJECTIVES: To examine whether measurement of insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein (IGFBP)-2 or IGFBP-3, alone or in combination, enhanced the specificity of prostate cancer detection among men with a prostate-specific antigen (PSA) level of 3 ng/mL or greater beyond that achieved by the free/total PSA index. METHODS: Cross-sectional analysis was performed on blood samples taken from 597 asymptomatic men (79% of those biopsied) participating in a community case-finding exercise. All men had a total PSA level of 3 ng/mL or greater and had undergone prostate biopsy. Assays of IGF-I, IGF-II, IGFBP-2, IGFBP-3, and free and total PSA were performed. The predictive performance of a range of measures was assessed using receiver operating characteristic analyses and compared with the free/total PSA index, for all biopsies and for men with a PSA level of 3 to 10 ng/mL. The overall test performance was summarized using the area under the receiver operating characteristic curve (AUC). RESULTS: Of the 597 men, 185 (31.0%) had prostate cancer identified at biopsy. When all biopsies were included, the performance of the free/total PSA index (AUC 0.73) was significantly greater than for IGF-I (AUC 0.59; P <0.0001), IGF-I/PSA ratio (AUC 0.65; P = 0.002), IGF-I + IGFBP-3 (AUC 0.59; P <0.0001), IGF-II (AUC 0.66; P = 0.002), and IGF-II + IGFBP-3 (AUC 0.67; P = 0.05). The combined measurement of free/total PSA, IGF-II, and IGFBP-3 resulted in a slight improvement in performance (AUC 0.76; P = 0.01). The results were similar when the analyses were restricted to men with an initial PSA level of 3 to 10 ng/mL. CONCLUSIONS: We found no evidence that measurement of the IGF axis enhances the specificity of prostate cancer detection in clinical practice beyond that achievable using the free/total PSA index.

Serum insulin-like growth factor-I is positively associated with serum prostate-specific antigen in middle-aged men without evidence of prostate cancer.

We have examined the relationship between serum insulin-like growth factor-I (IGF-I) and prostate-specific antigen in 367 healthy men without evidence of prostate cancer and found a positive association (P = 0.05). In men without prostate cancer, serum prostate-specific antigen is closely related to prostate size, and our findings, therefore, suggest that IGF-I may induce prostatic epithelial proliferation. Higher circulating levels of IGF-I have been associated with increased risk of both prostate cancer and possibly benign prostatic hyperplasia. Greater rates of cell proliferation induced by IGF-I may be a key biological pathway underlying these disorders.

Screen-detected prostate cancer and the insulin-like growth factor axis: results of a population-based case-control study.

Higher circulating levels of IGF-I have been associated with increased risk of prostate and some other cancers. Most research on prostate cancer has been based on men with symptoms or identified following treatment of benign disease. However, increasing numbers of cancer cases are now detected in asymptomatic men following prostate-specific antigen (PSA) tests. We therefore used a population-based case-finding exercise using the PSA test to examine whether associations between the IGF axis and cancer risk were apparent in this population. A matched case-control study was conducted among 7,383 men (50-70 years) receiving a PSA test as part of a case-finding exercise. Assays of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 were performed on cases and 2 controls matched on age, recruitment center and calendar time. Analyses were based on 176 cases and 324 matched controls. The risk of prostate cancer increased across quartiles of IGF-I (highest vs. lowest quartile, OR = 2.34; 95% CI = 1.26-4.34; p(trend) = 0.02) and IGF-II (OR = 1.78; 95% CI = 0.94-3.15; p(trend) = 0.09). Controlling for smoking history and IGFBP-3 strengthened associations with cancer for both IGF-I (OR = 3.00; 95% CI = 1.50-6.01; p(trend) 0.005) and IGF-II (OR = 2.02; 95% CI = 1.07-3.84; p(trend) = 0.04) Associations between the IGFs and cancer risk were stronger for advanced cases. Our findings suggest that both IGF-I and IGF-II are associated with an increased risk of screen-detected prostate cancer.

Who can best recruit to randomized trials? Randomized trial comparing surgeons and nurses recruiting patients to a trial of treatments for localized prostate cancer (the ProtecT study).

BACKGROUND AND OBJECTIVE: Recruitment to randomized trials is often difficult, but few studies have investigated interventions to improve recruitment. In a randomized trial nested within a trial of treatments for localized prostate cancer, we investigated the comparative effectiveness and cost-effectiveness of nurses and surgeons in recruiting patients. METHODS: Men with localized prostate cancer were randomized to see a nurse or urologic surgeon for an "information appointment" in which they were asked to consent to the ProtecT treatment trial comparing surgery, radiotherapy, and active monitoring. Analysis was conducted by intention to treat using chi-square with 95% confidence intervals for proportions and differences between groups. An economic evaluation was performed using the duration of appointments and grade of recruitment staff. RESULTS: Case-finding identified 167 men with localized prostate cancer. One hundred fifty (90%) took part in the recruitment trial. There was a 4.0% difference between nurses and surgeons in recruitment rates (67% nurses, 71% urologists, 95% CI -10.8% to +18.8%, P=.60). Cost-minimization analysis showed that nurses spent longer times with patients but surgeon costs were higher and nurses often supported surgeon-led clinics. CONCLUSION: Nurses were as effective and more cost-effective recruiters than urologic surgeons. This suggests an increased role for nurses in recruiting patients to randomized trials.