Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.

BACKGROUND: Between 1999 and 2009 in the United Kingdom, 82,429 men between 50 and 69 years of age received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed in 2664 men. Of these men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy. METHODS: At a median follow-up of 15 years (range, 11 to 21), we compared the results in this population with respect to death from prostate cancer (the primary outcome) and death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy (secondary outcomes). RESULTS: Follow-up was complete for 1610 patients (98%). A risk-stratification analysis showed that more than one third of the men had intermediate or high-risk disease at diagnosis. Death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P = 0.53 for the overall comparison). Death from any cause occurred in 356 men (21.7%), with similar numbers in all three groups. Metastases developed in 51 men (9.4%) in the active-monitoring group, in 26 (4.7%) in the prostatectomy group, and in 27 (5.0%) in the radiotherapy group. Long-term androgen-deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively. In the active-monitoring group, 133 men (24.4%) were alive without any prostate cancer treatment at the end of follow-up. No differential effects on cancer-specific mortality were noted in relation to the baseline PSA level, tumor stage or grade, or risk-stratification score. No treatment complications were reported after the 10-year analysis. CONCLUSIONS: After 15 years of follow-up, prostate cancer-specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer. (Funded by the National Institute for Health and Care Research; ProtecT Current Controlled Trials number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.).

Measuring quality of dying, death and end-of-life care for children and young people: A scoping review of available tools.

BACKGROUND: The circumstances and care provided at the end of a child's life have a profound impact on family members. Although assessing experiences and outcomes during this time is challenging, healthcare professionals have a responsibility to ensure high quality of care is provided. AIM: To identify available tools which measure the quality of dying, death and end-of-life care for children and young people; describe the content, and data on validity and reliability of existing tools. DESIGN: Scoping review was conducted following the Arksey and O'Malley methodological framework. DATA SOURCES: Four electronic databases (MEDLINE, EMBASE, CINAHL and PsycINFO) and grey literature were searched for studies published in English (January 2000-June 2021). A review of reference lists and citation searching was also undertaken. Tools needed to include a focus on the 'dying' phase of illness (defined as the last month of life). RESULTS: From 2078 articles, a total of 18 studies, reporting on 11 tools were identified. All tools were completed by primary caregivers or healthcare professionals as 'proxy' assessments; all except one was undertaken after death. Question items about quality of life and preparation for death were found in all tools; items relating to cultural aspects of care, grief and financial costs were less common. Only 6/11 had undergone psychometric testing within a paediatric palliative care setting. CONCLUSIONS: Future research should include ways to adapt, refine and improve existing tools. Assessing their wider application in different clinical and cultural settings and conducting further psychometric assessment represent areas of focus.

Active monitoring, radical prostatectomy and radical radiotherapy in PSA-detected clinically localised prostate cancer: the ProtecT three-arm RCT.

BACKGROUND: Prostate cancer is the most common cancer among men in the UK. Prostate-specific antigen testing followed by biopsy leads to overdetection, overtreatment as well as undertreatment of the disease. Evidence of treatment effectiveness has lacked because of the paucity of randomised controlled trials comparing conventional treatments. OBJECTIVES: To evaluate the effectiveness of conventional treatments for localised prostate cancer (active monitoring, radical prostatectomy and radical radiotherapy) in men aged 50-69 years. DESIGN: A prospective, multicentre prostate-specific antigen testing programme followed by a randomised trial of treatment, with a comprehensive cohort follow-up. SETTING: Prostate-specific antigen testing in primary care and treatment in nine urology departments in the UK. PARTICIPANTS: Between 2001 and 2009, 228,966 men aged 50-69 years received an invitation to attend an appointment for information about the Prostate testing for cancer and Treatment (ProtecT) study and a prostate-specific antigen test; 82,429 men were tested, 2664 were diagnosed with localised prostate cancer, 1643 agreed to randomisation to active monitoring (n = 545), radical prostatectomy (n = 553) or radical radiotherapy (n = 545) and 997 chose a treatment. INTERVENTIONS: The interventions were active monitoring, radical prostatectomy and radical radiotherapy. TRIAL PRIMARY OUTCOME MEASURE: Definite or probable disease-specific mortality at the 10-year median follow-up in randomised participants. SECONDARY OUTCOME MEASURES: Overall mortality, metastases, disease progression, treatment complications, resource utilisation and patient-reported outcomes. RESULTS: There were no statistically significant differences between the groups for 17 prostate cancer-specific (p = 0.48) and 169 all-cause (p = 0.87) deaths. Eight men died of prostate cancer in the active monitoring group (1.5 per 1000 person-years, 95% confidence interval 0.7 to 3.0); five died of prostate cancer in the radical prostatectomy group (0.9 per 1000 person-years, 95% confidence interval 0.4 to 2.2 per 1000 person years) and four died of prostate cancer in the radical radiotherapy group (0.7 per 1000 person-years, 95% confidence interval 0.3 to 2.0 per 1000 person years). More men developed metastases in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring, n = 33 (6.3 per 1000 person-years, 95% confidence interval 4.5 to 8.8); radical prostatectomy, n = 13 (2.4 per 1000 person-years, 95% confidence interval 1.4 to 4.2 per 1000 person years); and radical radiotherapy, n = 16 (3.0 per 1000 person-years, 95% confidence interval 1.9 to 4.9 per 1000 person-years; p = 0.004). There were higher rates of disease progression in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring (n = 112; 22.9 per 1000 person-years, 95% confidence interval 19.0 to 27.5 per 1000 person years); radical prostatectomy (n = 46; 8.9 per 1000 person-years, 95% confidence interval 6.7 to 11.9 per 1000 person-years); and radical radiotherapy (n = 46; 9.0 per 1000 person-years, 95% confidence interval 6.7 to 12.0 per 1000 person years; p < 0.001). Radical prostatectomy had the greatest impact on sexual function/urinary continence and remained worse than radical radiotherapy and active monitoring. Radical radiotherapy's impact on sexual function was greatest at 6 months, but recovered somewhat in the majority of participants. Sexual and urinary function gradually declined in the active monitoring group. Bowel function was worse with radical radiotherapy at 6 months, but it recovered with the exception of bloody stools. Urinary voiding and nocturia worsened in the radical radiotherapy group at 6 months but recovered. Condition-specific quality-of-life effects mirrored functional changes. No differences in anxiety/depression or generic or cancer-related quality of life were found. At the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year, the probabilities that each arm was the most cost-effective option were 58% (radical radiotherapy), 32% (active monitoring) and 10% (radical prostatectomy). LIMITATIONS: A single prostate-specific antigen test and transrectal ultrasound biopsies were used. There were very few non-white men in the trial. The majority of men had low- and intermediate-risk disease. Longer follow-up is needed. CONCLUSIONS: At a median follow-up point of 10 years, prostate cancer-specific mortality was low, irrespective of the assigned treatment. Radical prostatectomy and radical radiotherapy reduced disease progression and metastases, but with side effects. Further work is needed to follow up participants at a median of 15 years. TRIAL REGISTRATION: Current Controlled Trials ISRCTN20141297. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 37. See the National Institute for Health Research Journals Library website for further project information.

Prostate cancer is the most common cancer in men and is often found through a blood test called a prostate-specific antigen test and through biopsies of the prostate. Over the years, these tests led to the detection of many small cancers that do not cause harm. Some prostate cancers are harmful, but it is difficult to recognise them early. When cancer is still inside the prostate, the conventional treatments are surgery or radiotherapy, which carry side effects including leaking urine and difficulty getting an erection, so another option is repeat investigations at regular intervals (active monitoring), with treatments given if the cancer progresses. These options needed to be compared in a study called a 'randomised trial' in which men agree to be allocated to one of the three treatments. In the Prostate testing for cancer and Treatment (ProtecT) study, 200,000 men aged 50­69 years were invited to have a prostate-specific antigen test. Of the 82,849 men who agreed to be tested, 1643 of whom had prostate cancer that was still contained in the prostate agreed to be allocated to one of the three treatments. After an average of 10 years of follow-up, 99% of men were alive in each of the treatment groups. However, when compared with active monitoring, surgery and radiotherapy reduced the risk of disease spreading outside the prostate by half. Patients reported that urinary leakage and sexual function were worst with surgery, and sexual and bowel functions were affected by radiotherapy. Men on active monitoring had a gradual decline in their urinary and sexual function, particularly as around half of them later had surgery or radiotherapy. Radiotherapy was the treatment that seemed to be the best value for money. The findings from the Prostate testing for cancer and Treatment (ProtecT) study can help men make decisions about being tested and which treatment to have if they are found to have cancer within the prostate. We now need to find out the longer-term effects of these treatments on how long men live and their quality of life.

Self-disgust mediates the relationship between childhood adversities and psychosis.

OBJECTIVE: Traumatic events in childhood have been implicated in the development of psychosis, but given that trauma is not in itself sufficient to cause psychosis, researchers have started to investigate other psychological constructs potentially involved in explaining this relationship. Given that self-disgust as a transdiagnostic construct plays a role in the development/maintenance of a range of mental health difficulties, the objective of this study was to investigate whether self-disgust mediates the relationship between childhood trauma and psychosis. METHOD: A cross-sectional quantitative study design was used. Seventy-eight participants (Mage  = 37.64 years, SDage  = 11.57 years; 77% women; 88% White Caucasian) who reported experiencing clinical levels of psychosis were recruited using social media. The participants completed online survey measures of childhood trauma, self-disgust, experiences of psychosis, self-esteem, and external shame. The data were analysed using correlation and mediation analyses. RESULTS: Significant indirect effects of childhood trauma on both positive (ß = .17, BC 95% CI [0.06, 0.30]) and negative symptoms (ß = .26, BC 95% CI [0.14, 0.40]) of psychosis via self-disgust were observed. These effects remained despite the inclusion of self-esteem and external shame as control variables in the mediation models. CONCLUSION: This study is the first to show a mediating role for self-disgust in the relationship between childhood trauma and later psychosis. Although the findings should be considered preliminary until strengthened by further research, they nevertheless provide corroboration of the potential utility of self-disgust as a transdiagnostic construct not only from a theoretical perspective, but also from its potential to inform formulation and interventions. PRACTITIONER POINTS: When assessing individuals with psychosis, especially those with a trauma history explore experiences and feelings related to the construct of self-disgust. Such experiences are likely to centre on feelings of repulsion towards the self/need for distance and might also manifest in the content of their psychotic experiences. Individuals with significant levels or experiences of self-disgust are likely to need specific interventions to address these; while interventions seeking to improve positive aspects of their identity might well be useful, they are unlikely to address the specific maladaptive elements of self-disgust. While self-disgust-focused interventions have not been widely researched, limited current evidence suggests cognitive restructuring and affirmation techniques might be useful.

Self-disgust, loneliness and mental health outcomes in older adults: An eye-tracking study.

BACKGROUND: Self-disgust has been associated with loneliness and mental health difficulties in clinical and non-clinical populations, but there is limited research on the role of self-disgust in loneliness and mental health outcomes in older adults. METHODS: In Study 1 (N = 102; M age = 68.4 years, SD = 10.9, 68% females) we used a cross-sectional survey to explore the association between loneliness, self-disgust and mental health outcomes. In Study 2 (N = 80; M age = 68.8 years, SD = 11.4, 57% females) we used eye-tracking to investigate attentional vigilance, maintenance and avoidance in individuals with high (vs. low) self-disgust. RESULTS: In study 1 we found that self-disgust mediated the associations of loneliness with anxiety and depressive symptoms, and in study 2 it was demonstrated that older adults with high (vs. low) self-disgust displayed attentional avoidance to their own faces, compared to the faces of unknown others, a process that may perpetuate loneliness. LIMITATIONS: The cross-sectional design used in Study 1 limits our potential to make causal inferences. Additionally, both studies included a wide age range of older adults. CONCLUSIONS: Our findings are novel and highlight the importance of self-disgust experiences in the context of loneliness and mental health outcomes in older adults. Implications for practice and interventions against loneliness in this age group are discussed.

Disgust propensity has a causal link to the stigmatization of people with cancer.

Disgust-driven stigma may be motivated by an assumption that a stigmatized target presents a disease threat, even in the absence of objective proof. Accordingly, even non-contagious diseases, such as cancer, can become stigmatized by eliciting disgust. This study had two parts: a survey (n = 272), assessing the association between disgust traits and cancer stigma; and an experiment, in which participants were exposed to a cancer surgery (n = 73) or neutral video (n = 68), in order to test a causal mechanism for the abovementioned association. Having a higher proneness to disgust was associated with an increased tendency to stigmatize people with cancer. Further, a significant causal pathway was observed between disgust propensity and awkwardness- and avoidance-based cancer stigma via elevated disgust following cancer surgery exposure. In contrast, those exposed to cancer surgery not experiencing elevated disgust reported less stigma than controls. Exposure-based interventions, which do not elicit disgust, may be profitable in reducing cancer stigma.

Prosthesis use is associated with reduced physical self-disgust in limb amputees.

Self-disgust is an emotion schema negatively affecting people's body image and is triggered by bodily imperfections and deviations from the "normal" body envelope. In this study, we explore the idea that "normalising" the body in those with limb amputations via the prosthesis would be linked to reduced self-directed disgust. An international clinical community sample (N = 83) with mostly lower limb amputations completed measures about their demographics, prosthesis, adjustment, body image disturbance, psychological distress, and self-directed disgust in a survey design. Consistent with the "normalising" hypothesis, correlation and bootstrapped regression models revealed, first, that frequency of prosthesis use was significantly and negatively associated with physical self-disgust. Second, prosthesis use significantly mediated the exogenous effect of time since amputation on physical self-disgust. These results emphasise the psychological value of the prosthesis beyond its functional use, and stress its importance in normalising the body envelope in those with limb amputations, which may in turn promote psychological well-being.

Effect of Partners' Disgust Responses on Psychological Wellbeing in Cancer Patients.

The aim of this study was to explore quantitatively the relationship between disgust responses in cancer patients and their partners, and in turn their relationship to patients' psychological well-being. We recruited 50 participants with heterogeneous cancer diagnoses and their partners from cancer-related groups (e.g., charities). Patients completed questionnaires to determine levels of disgust propensity, disgust sensitivity, self-disgust, and symptoms of anxiety and depression. Disgust propensity and sensitivity were also assessed in their partners. Partners' disgust sensitivity was significantly positively correlated with cancer patients' self-disgust, disgust propensity, and depression. Path analyses suggested that patients' self-disgust plays a role in mediating the effect of partners' disgust sensitivity on patients' psychological well-being. This study provides the first quantitative evidence that psychological well-being in cancer patients is contingent on their partners' sensitivity to disgust, and that patients' self-disgust plays a mediating role. Focusing therapeutically on disgust responses could well be beneficial to people with cancer.

Mortality Among Men with Advanced Prostate Cancer Excluded from the ProtecT Trial.

BACKGROUND: Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates. OBJECTIVE: To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial. DESIGN, SETTING, AND PARTICIPANTS: Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression. RESULTS AND LIMITATIONS: Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0=5, M1=32) and 305 had locally advanced disease (62%). The median PSA was 17µg/l. Treatments included radical prostatectomy (RP; n=54; 11%), radiotherapy (RT; n=245; 50%), androgen deprivation therapy (ADT; n=122; 25%), other treatments (n=11; 2%), and unknown (n=60; 12%). There were 49 PCa-specific deaths (10%), of whom 14 men had received radical treatment (5%); and 129 all-cause deaths (26%). In matched ProtecT and ACN cohorts, 37 (9%) and 64 (16%), respectively, died of PCa, while 89 (22%) and 103 (26%) died of all causes. ProtecT men had a 45% lower risk of death from PCa compared to matched cases (hazard ratio 0.55, 95% confidence interval 0.38-0.83; p=0.0037), but mortality was similar in those treated radically. The nonrandomised design is a limitation. CONCLUSIONS: Men with PSA-detected advanced PCa excluded from ProtecT and treated radically had low rates of PCa death at 7.4-yr follow-up. Among men who underwent nonradical treatment, the ProtecT group had a lower rate of PCa death. Early detection through PSA testing, leadtime bias, and group heterogeneity are possible factors in this finding. PATIENT SUMMARY: Prostate cancer that has spread outside the prostate gland without causing symptoms can be detected via prostate-specific antigen testing and treated, leading to low rates of death from this disease.

Differential disgust responding in people with cancer and implications for psychological wellbeing.

OBJECTIVES: Evidence suggests that disgust responses, known to negatively affect psychological wellbeing, may differ in people with cancer. We performed the first quantitative investigation of three discrete types of disgust trait - disgust propensity, sensitivity and self-directed disgust - in people diagnosed with a broad range of cancers (versus cancer-free controls), and explored their associations with psychological wellbeing. DESIGN: In a cross-sectional survey design, 107 participants with heterogeneous cancer diagnoses, recruited from cancer charities and support groups, were matched with cancer-free controls by age and gender. OUTCOME MEASURES: Measures of the three disgust traits were taken alongside measures of anxiety and depression. RESULTS: Disgust sensitivity and physical self-disgust were significantly higher in the cancer than control sample, while disgust propensity and behavioural self-disgust were lower. The disgust traits had a different pattern of associations to psychological wellbeing across the two groups, with disgust sensitivity predicting depressive symptoms to a significantly greater extent in the cancer than control group. CONCLUSIONS: People with cancer differ from matched controls in their disgust responses and these responses have significant predictive relationships with aspects of their psychological wellbeing. The results suggest that emotion-based interventions may be useful for improving psychological wellbeing in people with cancer.

10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer.

BACKGROUND: The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. METHODS: We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. RESULTS: There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P<0.001 for the overall comparison). CONCLUSIONS: At a median of 10 years, prostate-cancer-specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring. (Funded by the National Institute for Health Research; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

The effect of disgust-related side-effects on symptoms of depression and anxiety in people treated for cancer: a moderated mediation model.

As maladaptive disgust responses are linked to mental health problems, and cancer patients may experience heightened disgust as a result of treatments they receive, we explored the associations between disgust-related side-effects and symptoms of depression and anxiety in people treated for cancer. One hundred and thirty two (83 women, M age = 57.48 years) participants answered questions about their treatments, side-effects, disgust responding, and mental health. Experiencing bowel and/or bladder problems, sickness and/or nausea (referred to here as "core" disgust-related side-effects) was significantly related to greater symptoms of depression and borderline increased anxiety. Further, these links were explained by a moderated mediation model, whereby the effects of core disgust side-effects on depression and anxiety were mediated by (physical and behavioural) self-directed disgust, and disgust propensity moderated the effect of core disgust side-effects on self-disgust. These findings stress the importance of emotional responses, like disgust, in psychological adaptation to the side-effects of cancer treatments.

EORTC Nomograms and Risk Groups for Predicting Recurrence, Progression, and Disease-specific and Overall Survival in Non-Muscle-invasive Stage Ta-T1 Urothelial Bladder Cancer Patients Treated with 1-3 Years of Maintenance Bacillus Calmette-Guérin.

BACKGROUND: There are no prognostic factor publications on stage Ta-T1 non-muscle-invasive bladder cancer (NMIBC) treated with 1-3 yr of maintenance bacillus Calmette-Guérin (BCG). OBJECTIVE: To determine prognostic factors in NMIBC patients treated with 1-3 yr of BCG after transurethral resection of the bladder (TURB), to derive nomograms and risk groups, and to identify high-risk patients who should be considered for early cystectomy. DESIGN, SETTING, AND PARTICIPANTS: Data for 1812 patients were merged from two European Organization for Research and Treatment of Cancer randomized phase 3 trials in intermediate- and high-risk NMIBC. INTERVENTION: Patients received 1-3 yr of maintenance BCG after TURB and induction BCG. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prognostic factors for risk of early recurrence and times to late recurrence, progression, and death were identified in a training data set using multivariable models and applied to a validation data set. RESULTS AND LIMITATIONS: With a median follow-up of 7.4 yr, 762 patients recurred; 173 progressed; and 520 died, 83 due to bladder cancer (BCa). Statistically significant prognostic factors identified by multivariable analyses were prior recurrence rate and number of tumors for recurrence, and tumor stage and grade for progression and death due to BCa. T1G3 patients do poorly, with 1- and 5-yr disease-progression rates of 11.4% and 19.8%, respectively, and 1- and 5-yr disease-specific death rates of 4.8% and 11.3%. Limitations include lack of repeat transurethral resection in high-risk patients and exclusion of patients with carcinoma in situ. CONCLUSIONS: NMIBC patients treated with 1-3 yr of maintenance BCG have a heterogeneous prognosis. Patients at high risk of recurrence and/or progression do poorly on currently recommended maintenance schedules. Alternative treatments are urgently required. PATIENT SUMMARY: Non-muscle-invasive bladder cancer patients at high risk of recurrence and/or progression do poorly on currently recommended bacillus Calmette-Guérin maintenance schedules, and alternative treatments are urgently required. TRIAL REGISTRATION: Study 30911 was registered with the US National Cancer Institute clinical trials database (protocol ID: EORTC 30911). Study 30962 was registered at ClinicalTrials.gov, number NCT00002990; http://clinicaltrials.gov/ct2/show/record/NCT00002990.

Long-term efficacy results of EORTC genito-urinary group randomized phase 3 study 30911 comparing intravesical instillations of epirubicin, bacillus Calmette-Guérin, and bacillus Calmette-Guérin plus isoniazid in patients with intermediate- and high-risk stage Ta T1 urothelial carcinoma of the bladder.

BACKGROUND: Intravesical chemotherapy and bacillus Calmette-Guérin (BCG) reduce the recurrence rate in patients with stage Ta T1 urothelial bladder cancer; however, the benefit of BCG relative to chemotherapy for long-term end points is controversial, especially in intermediate-risk patients. OBJECTIVE: The aim of the study was to compare the long-term efficacy of BCG and epirubicin. DESIGN, SETTING, AND PARTICIPANTS: From January 1992 to February 1997, 957 patients with intermediate- or high-risk stage Ta T1 urothelial bladder cancer were randomized after transurethral resection to one of three treatment groups in the European Organization for Research and Treatment of Cancer Genito-Urinary Group phase 3 trial 30911. INTERVENTION: Patients received six weekly instillations of epirubicin, BCG, or BCG plus isoniazid (INH) followed by three weekly maintenance instillations at months 3, 6, 12, 18, 24, 30, and 36. MEASUREMENTS: End points were time to recurrence, progression, distant metastases, overall survival, and disease-specific survival. RESULTS AND LIMITATIONS: With 837 eligible patients and a median follow-up of 9.2 yr, time to first recurrence (p<0.001), distant metastases (p=0.046), overall survival (p=0.023), and disease-specific survival (p=0.026) were significantly longer in the two BCG arms combined as compared with epirubicin; however, there was no difference for progression. Three hundred twenty-three patients with stage T1 or grade 3 tumors were high risk, and the remaining 497 patients were intermediate risk. The observed treatment benefit was at least as large, if not larger, in the intermediate-risk patients compared with the high-risk patients. CONCLUSIONS: In patients with intermediate- and high-risk stage Ta and T1 urothelial bladder cancer, intravesical BCG with or without INH is superior to intravesical epirubicin not only for time to first recurrence but also for time to distant metastases, overall survival, and disease-specific survival. The benefit of BCG is not limited to just high-risk patients; intermediate-risk patients also benefit from BCG. TRIAL REGISTRATION: This study was registered with the US National Cancer Institute clinical trials database [protocol ID: EORTC-30911]. http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=77075&version=HealthProfessional&protocolsearchid=6540260.

Population-based prostate-specific antigen testing in the UK leads to a stage migration of prostate cancer.

OBJECTIVE: To determine, within the UK, the stage and grade of prostate cancers that would be found through population-based prostate specific antigen (PSA) testing and biopsy. SUBJECTS AND METHODS: In the 'Prostate Testing for Cancer and Treatment' trial (ProtecT), men aged 50-69 years were recruited from nine cities in the UK and from randomly selected practices of general practitioners. Those with a PSA level of >3 ng/mL were offered a prostate biopsy. Age, PSA, stage and grade at diagnosis of ProtecT participants with cancer were compared with contemporaneous incident cases aged 50-69 years (age-restricted Cancer Registry cases) registered with the Eastern Cancer Registration and Information Centre (ECRIC). RESULTS: Within ProtecT, 94,427 men agreed to be tested (50% of men contacted), 8807 ( approximately 9%) had a raised PSA level and 2022 (23%) had prostate cancer; 229 ( approximately 12%) had locally advanced (T3 or T4) or metastatic cancers, the rest having clinically localized (T1c or T2) disease. Within ECRIC, 12,661 cancers were recorded over the same period; 3714 were men aged 50-69 years at diagnosis. Men in ProtecT had a lower age distribution and PSA level, and the cancers were of lower stage and grade (P < 0.001 for all comparisons). If population-based PSA testing were introduced in the UK, approximately 2660 men per 100,000 aged 50-69 years would be found to have prostate cancer, compared to current rates of approximately 130 per 100,000. If half of men accepted PSA testing, approximately 160,000 cancers would be found, compared to 30,000 diagnosed each year at present. CONCLUSIONS: Population-based PSA testing resulted in a significant downward stage and grade migration, and most such cancers were of low stage and grade, which could lead to risks of over-treatment for some men.

Development of a complex intervention improved randomization and informed consent in a randomized controlled trial.

OBJECTIVE: Multicenter randomized trials are required for pragmatic evaluations of health care interventions, but recruitment is difficult. Systematic reviews failed to identify robust strategies to improve recruitment. We developed and evaluated a complex intervention to increase levels of randomization and informed consent. STUDY DESIGN AND SETTING: The ProtecT (Prostate testing for cancer and Treatment) trial compares radical surgery, radical conformal radiotherapy, and active monitoring for men aged 50-69 years with localized prostate cancer. The intervention was developed using qualitative research methods (content, thematic and conversation analysis). Rates of randomization and immediate acceptance of allocation were measured every 6 months to evaluate the impact of the intervention. RESULTS: The complex intervention comprised reviews of centers falling below study targets, training programmes, documents and individually tailored feedback. Over 65% of eligible participants consented to randomization. Trial participants became increasingly well informed as immediate acceptance of allocation rose from 65% to 81% between 2001 and 2005. CONCLUSION: This complex intervention resulted in high levels of randomization and informed consent in a difficult trial. The generic aspects of the intervention could be applied to other trials to maximize randomization and informed consent, and allow the mounting of trials previously considered too difficult.

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.