A cohort profile of the Graham Roberts study cohort.

Purpose: The Graham Roberts Study was initiated in 2018 and is the first Trials Within Cohorts (TwiCs) study for bladder cancer. Its purpose is to provide an infrastructure for answering a breadth of research questions, including clinical, mechanistic, and supportive care centred questions for bladder cancer patients. Participants: All consented patients are those aged 18 or older, able to provide signed informedconsent and have a diagnosis of new or recurrent bladder cancer. All patients are required to have completed a series of baseline questionnaires. The questionnaires are then sent out every 12 months and include information on demographics and medical history as well as questionnaires to collect information on quality of life, fatigue, depression, overall health, physical activity, and dietary habits. Clinical information such as tumor stage, grade and treatment has also been extracted for each patient. Findings to date: To date, a total of 125 bladder cancer patients have been consented onto the study with 106 filling in the baseline questionnaire. The cohort is made up of 75% newly diagnosed bladder cancer patients and 66% non-muscle invasive bladder cancer cases. At present, there is 1-year follow-up information for 70 patients, 2-year follow-up for 57 patients, 3-year follow-up for 47 patients and 4-year follow-up for 19 patients. Future plans: We plan to continue recruiting further patients into the cohort study. Using the data collected within the study, we hope to carry out independent research studies with a focus on quality of life. We are also committed to utilizing the Roberts Study Cohort to set up and commence an intervention. The future studies and trials carried out using the Roberts Cohort have the potential to identify and develop interventions that could improve the prevention, diagnosis, and treatment of bladder cancer.

Designing a Pragmatic Intervention to Help Improve the Bladder Cancer Patient Experience.

Bladder cancer (BC) is the 10th most common malignancy worldwide and the patient experience is found to be worse than that for patients diagnosed with other cancer types. We aimed to develop a wellbeing intervention to help improve the bladder cancer patient experience by ameliorating their health-related Quality of Life (HRQoL). We followed the 3 phases of the modified Medical Research Council (MRC) Framework for development of complex interventions. Following a systematic review of the literature on mental, sexual, and physical wellbeing, we conducted discussion groups with patients and healthcare professionals on these 3 themes. A consultation phase was then conducted with all relevant stakeholders to co-design a wellbeing intervention as part of a feasibility study. A pragmatic wellbeing feasibility trial was designed based on the hypothesis that a wellbeing program will increase patient awareness and attendance to services available to them and will better support their needs to improve HRQoL. The primary feasibility endpoints are patient attendance to the services offered and changes in HRQoL. The principle of patient centered care has strengthened the commitment to provide a holistic approach to support BC patients. In this study, we developed a wellbeing intervention in collaboration with patients and healthcare professionals to meet an unmet need in terms of the BC patient experience.

Safety of "hot" and "cold" site admissions within a high-volume urology department in the United Kingdom at the peak of the COVID-19 pandemic.

OBJECTIVES: To determine the safety of urological admissions and procedures during the height of the COVID-19 pandemic using "hot" and "cold" sites. The secondary objective is to determine risk factors of contracting COVID-19 within our cohort. PATIENTS AND METHODS: A retrospective cohort study of all consecutive patients admitted from March 1 to May 31, 2020 at a high-volume tertiary urology department in London, United Kingdom. Elective surgery was carried out at a "cold" site requiring a negative COVID-19 swab 72-hours prior to admission and patients were required to self-isolate for 14-days preoperatively, while all acute admissions were admitted to the "hot" site.Complications related to COVID-19 were presented as percentages. Risk factors for developing COVID-19 infection were determined using multivariate logistic regression analysis. RESULTS: A total of 611 patients, 451 (73.8%) male and 160 (26.2%) female, with a median age of 57 (interquartile range 44-70) were admitted under the urology team; 101 (16.5%) on the "cold" site and 510 (83.5%) on the "hot" site. Procedures were performed in 495 patients of which eight (1.6%) contracted COVID-19 postoperatively with one (0.2%) postoperative mortality due to COVID-19. Overall, COVID-19 was detected in 20 (3.3%) patients with two (0.3%) deaths. Length of stay was associated with contracting COVID-19 in our cohort (OR 1.25, 95% CI 1.13-1.39). CONCLUSIONS: Continuation of urological procedures using "hot" and "cold" sites throughout the COVID-19 pandemic was safe practice, although the risk of COVID-19 remained and is underlined by a postoperative mortality.

Is there a role for physical activity interventions in the treatment pathway of bladder cancer? A scoping review of the literature.

INTRODUCTION: Physical activity (PA) interventions have been introduced in patients with cancer as they may contribute to better treatment outcomes and quality of life (QoL). However, little is known about the impact of PA on patients with bladder cancer (BC). This scoping review aimed to explore efficacy and feasibility of existing PA interventions in the BC care pathway. METHODS AND ANALYSIS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review guidelines and the Levac methodology framework were used; electronic databases were searched. Two independent reviewers screened all titles, abstracts and full-text publications for inclusion. The feasibility of integrating a PA intervention in the BC treatment pathway was discussed in a consultation phase with healthcare professionals and patient and public representatives. RESULTS: A total of 675 records were identified through database searching of which 14 studies were included in our scoping review. An additional 17 clinical trials were identified of which 12 were included for which no results have been published yet. The included studies looked at the feasibility of a PA intervention programme, the associations between PA, obesity and BC, but also the determinants of PA engagement for BC patients and the assessment of QoL. CONCLUSION: This scoping review highlights that despite the general recognition on the role of PA in the BC treatment pathway, there is a gap regarding the understanding of the impact of PA interventions in BC care pathways as well as the limited understanding of factors underlying possible benefits of PA. No clear conclusions could be made regarding structure and processes of PA interventions that may lead to better outcomes. Further PA studies for patients with BC are needed to understand how to incorporate exercise guidelines recommendations.

The need for supportive mental wellbeing interventions in bladder cancer patients: A systematic review of the literature.

OBJECTIVES: There is an increased awareness of the effect of a bladder cancer diagnosis and its treatments on the mental wellbeing of patients. However, few studies have evaluated the efficacy, feasibility and acceptability of interventions to improve this mental wellbeing. This systematic review is the first phase of the Medical Research Council Framework for developing complex interventions and provides an overview of the published mental wellbeing interventions that could be used to design an intervention specific for BC patients. METHODS: This review was conducted in accordance with the PRISMA guidelines in January 2019 and studies were identified by conducting searches for Medline, the Cochrane Central Register of Controlled Trials and Ovid Gateway. All included studies met the following criteria: mental wellbeing interventions of adults with medically confirmed diagnosis of any type of urological cancer, reported outcomes for specific HRQoL domains including psychological factors. The quality of evidence was assessed according to Down and Black 27-item checklist. RESULTS: A total of 15,094 records were collected from the literature search and 10 studies matched the inclusion and exclusion criteria. Of these, nine interventions were for patients with prostate cancer and one for patients with kidney cancer. No studies were found for other urological cancers. Depression was the most commonly reported endpoint measured. Of the included studies with positive efficacy, three were group interventions and two were couple interventions. In the group interventions, all showed a reduction in depressive symptoms and in the couple interventions, there was a reduction in depressive symptoms and a favourable relationship cohesion. The couple interventions were the most feasible and acceptable, but further research was required for most of the studies. CONCLUSION: While awareness of the importance of mental wellbeing in bladder cancer patients is growing, this systematic literature review highlights the gap of feasible and acceptable interventions for this patient population.

Unmet needs in sexual health in bladder cancer patients: a systematic review of the evidence.

BACKGROUND: Bladder cancer (BC) treatment can have a detrimental effect on the sexual organs of patients and yet assessment of sexual health needs has been greatly overlooked for these patients compared to those who have undergone other cancer therapies. METHODS: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines in July 2019. Studies were identified by conducting searches for Medline (using the PubMed interface), the Cochrane Central Register of Controlled Trials (CENTRAL) and Ovid Gateway (Embase and Ovid) using a list of defined search terms. RESULTS: 15 out of 37 studies included men only, 10 studies women only and 11 both sexes. Most participants were aged 50 to 65 years. Most studies (n = 34) focused on muscle invasive BC and only three on non-muscle invasive BC. Measurements of sexual dysfunction, including erection, ejaculation, firmness and desire, were the most commonly used measurements to report sexual health in men. In women, lubrification/dryness, desire, orgasm and dyspareunia were the most commonly reported. Twenty-one studies evaluated sexual dysfunction based on validated questionnaires, two with a non-validated questionnaire and through interviewing participants. CONCLUSION: While recognition of the importance of the inclusion of psychometric measurements to assess sexual health is growing, there is a lack of consistent measures to assess sexual health in BC. With the focus on QoL arising in cancer survivorship, further studies are needed to develop, standardize and implement use of sexual health questionnaires with appropriate psychometrics and social measures to evaluate QoL in BC patients. TRIAL REGISTRATION: "PROSPERO does not currently accept registrations for scoping reviews, literature reviews or mapping reviews. PROSPERO is therefore unable to accept your application or provide a registration number. This decision should not stop you from submitting your project for publication to a journal."

Graham Roberts Study protocol: first 'trials within cohort study' for bladder cancer.

INTRODUCTION: Given the need for more bladder cancer research and the recently observed advantages of introducing the trials within cohort (TwiCs) design, the set-up of the Graham Roberts Study (Roberts Study) will provide valuable infrastructure to answer a wide variety of research questions of a clinical, mechanistic, as well as supportive care nature in the area of bladder cancer. METHODS: Using the TwiCs design, we will recruit patients aged 18 or older who are willing and able to provide signed informed consent and have a diagnosis of new or recurrent bladder cancer into this prospective cohort study. All patients must have a basic understanding of the English language. The following questionnaires will be collected at baseline and every 12 months subsequently: Functional Assessment of Chronic Illness Therapy for Bladder Cancer, the Functional Assessment of Chronic Illness Therapy-Fatigue, the Patient Heath Questionnaire-9, the standardised instrument for a generic health status (EQ-5D-5L), a Short Questionnaire to Assess Health-Enhancing Physical Activity and the Hertfordshire Short Questionnaire to Assess Diet Quality. ETHICS AND DISSEMINATION: Due to the nature of this study, we obtained full ethical clearance from the London-Fulham Research Ethics Committee (17/LO1975). All participants must provide full informed consent before recruitment onto the study. The results of this study will be published in peer-reviewed journals and data collected as part of the study will be made available to potential collaborators on an application basis.

Sequential bacillus Calmette-Guérin/Electromotive Drug Administration of Mitomycin C as the Standard Intravesical Regimen in High Risk Nonmuscle Invasive Bladder Cancer: 2-Year Outcomes.

PURPOSE: Sequential bacillus Calmette-Guérin/electromotive drug administration of mitomycin C is reported to be superior to bacillus Calmette-Guérin alone but it has not been widely adopted. We aimed to determine the efficacy and tolerability of sequential bacillus Calmette-Guérin/electromotive drug administration of mitomycin C in high risk, nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Starting in 2009 bacillus Calmette-Guérin/electromotive drug administration of mitomycin C was introduced as the standard induction regime in patients with high risk, nonmuscle invasive bladder cancer undergoing bladder conservation. As induction bacillus Calmette-Guérin was administered in weeks 1 and 2. Mitomycin C was administered in electromotive fashion (40 mg and 20 mA current for 30 minutes) in week 3 and repeated thrice for a total of 9 weeks. As maintenance 3 doses of bacillus Calmette-Guérin were given 3 months after induction and then every 6 months for 3 years. Outcome measures were disease recurrence at first check, 1 and 2-year cystoscopy, and treatment tolerability. RESULTS: Of the 151 patients with high risk, nonmuscle invasive bladder cancer treated between June 2009 and 2013, 44 underwent primary cystectomy and 107 received sequential bacillus Calmette-Guérin/electromotive drug administration of mitomycin C. Disease was high grade Ta/T1 in 86 patients (80%), of whom 34 (32%) also had carcinoma in situ. A total of 19 patients (18%) had primary carcinoma in situ and 2 had recurrent large volume, low grade disease. Of 107 patients 104 underwent first check cystoscopy, including 90 (87%) who were clear. Of the 90 complete responders 86 underwent 1-year cystoscopy, including 74 (86%) who were recurrence-free. Of the 74 patients 71 underwent 2-year cystoscopy, of whom 66 (93%) remained recurrence-free. The full induction schedule was not completed in 30 patients (28%), including 16 and 14 with minor and major schedule alterations, respectively. There was no difference in recurrence between patients who received a full vs a reduced induction schedule. CONCLUSIONS: This study confirms the excellent oncologic efficacy of sequential bacillus Calmette-Guérin/electromotive drug administration of mitomycin C in cases of high risk, nonmuscle invasive bladder cancer. Tolerability is a challenge but alterations to the 9-week schedule appeared to have a negligible impact on outcomes.

Prospective randomized trial of hexylaminolevulinate photodynamic-assisted transurethral resection of bladder tumour (TURBT) plus single-shot intravesical mitomycin C vs conventional white-light TURBT plus mitomycin C in newly presenting non-muscle-invasive bladder cancer.

OBJECTIVE: To determine if photodynamic 'blue-light'-assisted resection leads to lower recurrence rates in newly presenting non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: We conducted a prospective randomized trial of hexylaminolevulinate (HAL) photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumour (TURBT) plus single-shot intravesical mitomycin C vs standard white-light-assisted TURBT plus single-shot intravesical mitomycin C. A total of 249 patients with newly presenting suspected NMIBC enrolled at Guy's Hospital between March 2005 and April 2010. Patients with a history of bladder cancer were excluded. The surgery was performed by specialist bladder cancer surgical teams. Of the eligible patients, 90% agreed to be randomized. RESULTS: Of the 249 patients, 209 (84%) had cancer and in 185 patients (89%) the cancer was diagnosed as NMIBC. There were no adverse events related to HAL in any of the patients randomized to the intravesical HAL-PDD arm. Single-shot intravesical mitomycin C was administered to 61/97 patients (63%) in the HAL-PDD arm compared with 68/88 patients (77%) in the white-light arm (P = 0.04) Intravesical HAL was an effective diagnostic tool for occult carcinoma in situ (CIS). Secondary CIS was identified in 25/97 patients (26%) in the HAL-PDD arm compared with 12/88 patients (14%) in the white-light arm ((P = 0.04) There was no significant difference in recurrence between the two arms at 3 or 12 months: in the HAL-PDD and the white-light arms recurrence was found in 17/86 and 14/82 patients (20 vs 17%), respectively ((P = 0.7) at 3 months, and in 10/63 and 15/67 patients (16 vs 22%), respectively ((P = 0.4) at 12 months. CONCLUSIONS: Despite HAL-PDD offering a more accurate diagnostic assessment of a bladder tumour, in this trial we did not show that this led to lower recurrence rates of newly presenting NMIBC compared with the best current standard of care.

Demonstration of erectile management techniques to men scheduled for radical prostatectomy reduces long-term regret: a comparative cohort study.

OBJECTIVE: To determine whether preoperative demonstrations of intracavernosal and vacuum therapies for erectile dysfunction (ED) influence the decision of treatment choice, reducing long-term regret. PATIENTS AND METHODS: In all, 82 consecutive men with localized prostate cancer, scheduled for radical prostatectomy and reporting an International Index of Erectile Function score of >21, were prospectively enrolled at a single cancer centre. Following standard preoperative counselling, half of the men were invited to attend a further consultation for intracavernosal and vacuum therapy demonstrations. All patients were evaluated pretreatment and then 3 monthly using the five-point International Index of Erectile Function score and the 14-item Hospital Anxiety and Depression scale. At 12 months treatment choice changes were recorded and patients were assessed for treatment choice regret using Clark's validated two-item regret questionnaire. Statistical analysis was performed using the Mann-Whitney and Fisher's exact tests. Results were compared with a control population of 41 men who did not undergo additional ED counselling. RESULTS: In all, 8/41 men (19%) changed their treatment choice, opting for brachytherapy rather than radical prostatectomy. Only 1/41 in the control population changed their decision before surgery. At 1 year, one patient (2%) in the intervention group expressed regret at his treatment choice (radical prostatectomy) compared with eight (20%) in the control group (P= 0.03, two-sided Fisher's exact test); ED was identified as the major cause of this regret. CONCLUSION: Preoperative demonstrations of ED therapies can optimize decision making in prostate cancer and help reduce long-term regret.

Hexylaminolaevulinate fluorescence cystoscopy in patients previously treated with intravesical bacille Calmette-Guérin.

OBJECTIVE To determine if hexylaminolaevulinate fluorescence cystoscopy (HAL-FC) has the potential to improve the diagnosis of bladder cancer in patients who have been treated with bacille Calmette-Guérin (BCG). PATIENTS AND METHODS Patients scheduled for rigid cystoscopy after BCG therapy were recruited prospectively between April 2005 and February 2006. Patients received HAL (Hexvix, PhotoCure ASA, Oslo, Norway) and the D-light system (Storz, Tuttlingen, Germany) was used to detect fluorescence. The bladder was mapped and biopsies taken under white light and then using HAL-FC. The main outcome was the frequency and nature of additional pathology detected by HAL-FC. Twenty-seven patients (21 men and six women; median age 70 years, range 49-82) underwent 32 HAL-FC. RESULTS Recurrent bladder cancer was detected in 11 of the 32 (34%) examinations. HAL-FC detected additional pathology in five of the 27 (19%) patients. In two of these cases the additional pathology was clinically significant (one pT4G3 intraprostatic transitional cell carcinoma and one intravesical pT1G2 + carcinoma in situ), whereas in three cases the pathology was hyperplasia/dysplasia. Overall, the false-positive biopsy rate with HAL-FC was 63%. In the presence of positive voided urine cytology six of eight patients had recurrent bladder tumour and the false-positive biopsy rate was only 34%. Urine cytology was positive in four of five of the patients in whom additional pathology was detected by HAL-FC. CONCLUSIONS Clinically significant occult pathology can be detected using HAL-FC after BCG therapy, but in <10% of cases. The rate of false-positive biopsies is high but in our hands appears to be lower than with white-light guided biopsies after BCG. Our pragmatic approach is to use HAL-FC after BCG when clinical suspicion is high, and when the preoperative voided urine cytology is positive.

Hexylaminolevulinate photodynamic diagnosis for multifocal recurrent nonmuscle invasive bladder cancer.

OBJECTIVE: To determine the potential for hexylaminolevulinate (HAL) photodynamic diagnosis (PDD) to improve the management of multifocal recurrent nonmuscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Patients with a history of NMIBC and with at least two suspected papillary recurrences were enrolled in this prospective study between April 2005 and October 2006. The photosensitizer was hexylaminolevulinate (HAL) (PhotoCure, Norway), and the Storz D-light system was used to detect fluorescence. The bladder was mapped initially under white light and then using HAL-photodynamic diagnosis (PDD). The number and types of additional lesions detected by HAL-PDD over white light cystoscopy were measured. RESULTS: Eighteen patients (11 men), median age 74 years (range 35-84 yrs), underwent HAL-PDD. The median HAL instillation time was 109 minutes (range 60-250 min). Recurrent bladder cancer was confirmed histologically in 14/18 (78%) patients. Additional pathology was detected in 8/14 (57%) patients with confirmed recurrence and confirmed histologically in 6 of these. Additional pathology was papillary in 5/6 (83%) patients, and flat pathology was found in all six patients with additional foci. Carcinoma in situ (CIS) was detected in 4/6 (67%) patients with additional foci, three of whom were subsequently treated with intravesical bacille Calmette-Guérin (BCG). The sensitivity of HAL-PDD for the detection of tumor was 97.8%, compared with 69.6% for white light cystoscopy. The false-positive fluorescence-guided biopsy rate was 18/63 (29%). CONCLUSION: HAL-PDD allows more complete management of bladder tumor in patients with multifocal recurrence. The high frequency of additional lesions detected and the rate of detection of CIS suggest that HAL-PDD should be the standard of care.

Hexylaminolaevulinate 'blue light' fluorescence cystoscopy in the investigation of clinically unconfirmed positive urine cytology.

OBJECTIVE: To investigate the value of photodynamic diagnosis (PDD) using hexylaminolaevulinate (Hexvix, PhotoCure, Oslo, Norway) in the investigation of patients with positive urine cytology who have no evidence of disease after standard initial investigations. PATIENTS AND METHODS: Twenty-three patients referred with positive urine cytology but no current histological evidence of cancer were investigated between April 2005 and January 2007 with PDD, using Hexvix and the D-light system (Karl Storz, Tuttlingen, Germany) to detect fluorescence. The bladder was mapped initially under white light and then under 'blue-light'. Biopsies were taken from abnormal urothelium detected by white light, fluorescence, or both. All cytological specimens were reviewed by a reference cytopathologist unaware of the result of the PDD. RESULTS: Twenty-five PDD-assisted cystoscopies were carried out on 23 patients (20 men/3 women; median age 64 years, range 24-80 years). Of the 23 patients, 17 (74%) were previously untreated for transitional cell carcinoma (TCC), whilst six were under surveillance for previous TCC. Nineteen of the 23 (83%) cytology specimens were confirmed as suspicious or positive by the reference pathologist. TCC of the bladder or preneoplastic lesions were diagnosed in six patients, i.e. six (26%) of those investigated and six of 19 (32%) with confirmed positive cytology. Four of the six were under surveillance for previous bladder tumour. Additional pathology was detected by fluorescence in five of the six patients, including two carcinoma in situ (CIS), one CIS + G3pT1 tumour, and two dysplasia. Diagnoses in PDD-negative cases included one upper tract TCC and four patients with stones. In addition, one patient had CIS diagnosed on both white light and PDD 6 months later. CONCLUSION: Additional pathology was detected by HAL fluorescence cystoscopy in 32% of patients with confirmed positive urinary cytology. PDD is a key step in the management of patients with positive urinary cytology and no evidence of disease on conventional tests.