Health-related quality of life after a diagnosis of bladder cancer: a longitudinal survey over the first year.

OBJECTIVES: To describe the health-related quality of life (HRQoL) of patients in a prospective 12-month observational cohort study of new bladder cancer diagnoses and compare with national cancer and general population surveys. PATIENTS AND METHODS: A prospective UK study in patients with new bladder cancer diagnoses at 13 NHS Trusts. The HRQoL data were collected at 3, 6, 9 and 12 months. Questionnaires used included: the EuroQoL five Dimensions (EQ-5D), European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ)-30-item core, EORTC QLQ-24-item non-muscle-invasive bladder cancer, and EORTC QLQ-30-item muscle-invasive bladder cancer. Results were compared with the Cancer Quality of Life Survey and Health Survey for England. RESULTS: A total of 349 patients were recruited, 296 (85%) completed the first (baseline) and 233 (67%) the final survey. The patients underwent transurethral resection of bladder tumour (TURBT) ± intravesical therapy (238 patients, 80%), radical cystectomy/radiotherapy (51, 17%) or palliation (seven, 2%). At baseline, patients needing radical treatment reported worse HRQoL including lower social function (74.2 vs 83.8, P = 0.002), increased fatigue (31.5 vs 26.1, P = 0.03) and more future worries (39.2 vs 29.4, P = 0.005) than patients who underwent TURBT. Post-treatment surveys showed no change/improvements for patients who underwent TURBT but deterioration for the radically treated cohort. At final survey, reports were similar to baseline, regardless of treatment. Radically treated patients continued to report poorer HRQoL including issues with body image (23.4 vs 12.5, P = 0.007) and male sexual function (75.8 vs 40.4, P < 0.001) compared to those who underwent TURBT. Radically treated patients reported lower EQ-5D utility scores and more problems with usual activities than the general population. DISCUSSION: Patients undergoing TURBT can be reassured regarding HRQoL following treatment. However, those requiring radical treatment report greater changes in HRQoL with the need for appropriate clinical and supportive care to minimise the impact of treatments.

Defining Factors Associated with High-quality Surgery Following Radical Cystectomy: Analysis of the British Association of Urological Surgeons Cystectomy Audit.

BACKGROUND: Radical cystectomy (RC) is associated with high morbidity. OBJECTIVE: To evaluate healthcare and surgical factors associated with high-quality RC surgery. DESIGN SETTING AND PARTICIPANTS: Patients within the prospective British Association of Urological Surgeons (BAUS) registry between 2014 and 2017 were included in this study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: High-quality surgery was defined using pathological (absence of positive surgical margins and a minimum of a level I lymph node dissection template with a minimum yield of ten or more lymph nodes), recovery (length of stay ≤10 d), and technical (intraoperative blood loss <500 ml for open and <300 ml for minimally invasive RC) variables. A multilevel hierarchical mixed-effect logistic regression model was utilised to determine the factors associated with the receipt of high-quality surgery and index admission mortality. RESULTS AND LIMITATIONS: A total of 4654 patients with a median age of 70.0 yr underwent RC by 152 surgeons at 78 UK hospitals. The median surgeon and hospital operating volumes were 23.0 and 47.0 cases, respectively. A total of 914 patients (19.6%) received high-quality surgery. The minimum annual surgeon volume and hospital volume of ≥20 RCs/surgeon/yr and ≥68 RCs/hospital/yr, respectively, were the thresholds determined to achieve better rates of high-quality RC. The mixed-effect logistic regression model found that recent surgery (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.11-1.34, p < 0.001), laparoscopic/robotic RC (OR: 1.85, 95% CI: 1.45-2.37, p < 0.001), and higher annual surgeon operating volume (23.1-33.0 cases [OR: 1.54, 95% CI: 1.16-2.05, p = 0.003]; ≥33.1 cases [OR: 1.64, 95% CI: 1.18-2.29, p = 0.003]) were independently associated with high-quality surgery. High-quality surgery was an independent predictor of lower index admission mortality (OR: 0.38, 95% CI: 0.16-0.87, p = 0.021). CONCLUSIONS: We report that annual surgeon operating volume and use of minimally invasive RC were predictors of high-quality surgery. Patients receiving high-quality surgery were independently associated with lower index admission mortality. Our results support the role of centralisation of complex oncology and implementation of a quality assurance programme to improve the delivery of care. PATIENT SUMMARY: In this registry study of patients treated with surgical excision of the urinary bladder for bladder cancer, we report that patients treated by a surgeon with a higher annual operative volume and a minimally invasive approach were associated with the receipt of high-quality surgery. Patients treated with high-quality surgery were more likely to be discharged alive following surgery.

Major Urological Cancer Surgery for Patients is Safe and Surgical Training Should Be Encouraged During the COVID-19 Pandemic: A Multicentre Analysis of 30-day Outcomes.

COVID-19 has resulted in the deferral of major surgery for genitourinary (GU) cancers with the exception of cancers with a high risk of progression. We report outcomes for major GU cancer operations, namely radical prostatectomy (RP), radical cystectomy (RC), radical nephrectomy (RN), partial nephrectomy (PN), and nephroureterectomy performed at 13 major GU cancer centres across the UK between March 1 and May 5, 2020. A total of 598 such operations were performed. Four patients (0.7%) developed COVID-19 postoperatively. There was no COVID-19-related mortality at 30 d. A minimally invasive approach was used in 499 cases (83.4%). A total of 228 cases (38.1%) were described as training procedures. Training case status was not associated with a higher American Society of Anesthesiologists (ASA) score (p = 0.194) or hospital length of stay (LOS; p > 0.05 for all operation types). The risk of contracting COVID-19 was not associated with longer hospital LOS (p = 0.146), training case status (p = 0.588), higher ASA score (p = 0.295), or type of hospital site (p = 0.303). Our results suggest that major surgery for urological cancers remains safe and training should be encouraged during the ongoing COVID-19 pandemic provided appropriate countermeasures are taken. These real-life data are important for policy-makers and clinicians when counselling patients during the current pandemic. PATIENT SUMMARY: We collected outcome data for major operations for prostate, bladder, and kidney cancers during the COVID-19 pandemic. These surgeries remain safe and training should be encouraged during the ongoing pandemic provided appropriate countermeasures are taken. Our real-life results are important for policy-makers and clinicians when counselling patients during the COVID-19 pandemic.

A Novel, non-invasive Test Enabling Bladder Cancer Detection in Urine Sediment of Patients Presenting with Haematuria-A Prospective Multicentre Performance Evaluation of ADXBLADDER.

Bladder cancer is the sixth most commonly diagnosed cancer in the European Union. Here, we evaluate the performance of a novel, commercially available enzyme-linked immunosorbent assay utilising MCM5 antibodies (ADXBLADDER; Arquer Diagnostics Ltd, Sunderland, UK) for the detection of bladder cancer, in a blinded, prospective study of 856 patients, across seven centres, presenting with haematuria. The results were compared with the patients' clinical data and final diagnosis as defined by the results of the imaging and cystoscopy, with a prevalence of bladder cancer of 8.6%. ADXBLADDER detected bladder tumours in 54/74 cancers, giving overall sensitivity of 73.0% and an overall negative predictive value (NPV) of 96.4%. Sensitivity and NPV of ADXBLADDER were highest in muscle-invasive bladder cancer, both at 100%, and on analysis of non-pTa (pT1 and above) tumours, the sensitivity for detection was 97% with an NPV of 99.8%. A subset of 173 patients had matching cytology data; of these patients, 18 were positive for bladder cancer. ADXBLADDER detected 16/18 of these cancers, whilst cytology was positive in only four of 18, providing evidence that ADXBLADDER may be a more sensitive test for bladder cancer than standard urine cytology. PATIENT SUMMARY: We conducted a large clinical study of a novel, simple urine test (ADXBLADDER), which measures a protein (MCM5) in urine and can be used to detect bladder cancer in patients. We recruited 856 patients and demonstrated that the new urine test can detect bladder cancer with a high degree of accuracy, performing better than the most commonly used urine test-urine cytology. In conclusion, this novel ADXBLADDER urine test can be used to help detect bladder cancers and it can replace the current, standard urine test.

BOXIT-A Randomised Phase III Placebo-controlled Trial Evaluating the Addition of Celecoxib to Standard Treatment of Transitional Cell Carcinoma of the Bladder (CRUK/07/004).

BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) has a significant risk of recurrence despite adjuvant intravesical therapy. OBJECTIVE: To determine whether celecoxib, a cyclo-oxygenase 2 inhibitor, reduces the risk of recurrence in NMIBC patients receiving standard treatment. DESIGN, SETTING, AND PARTICIPANTS: BOXIT (CRUK/07/004, ISRCTN84681538) is a double-blinded, phase III, randomised controlled trial. Patients aged ≥18 yr with intermediate- or high-risk NMIBC were accrued across 51 UK centres between 1 November 2007 and 23 July 2012. INTERVENTION: Patients were randomised (1:1) to celecoxib 200mg twice daily or placebo for 2 yr. Patients with intermediate-risk NMIBC were recommended to receive six weekly mitomycin C instillations; high-risk NMIBC cases received six weekly bacillus Calmette-Guérin and maintenance therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was time to disease recurrence. Analysis was by intention to treat. RESULTS AND LIMITATIONS: A total of 472 patients were randomised (236:236). With median follow-up of 44 mo (interquartile range: 36-57), 3-yr recurrence-free rate (95% confidence interval) was as follows: celecoxib 68% (61-74%) versus placebo 64% (57-70%; hazard ratio [HR] 0.82 [0.60-1.12], p=0.2). There was no difference in high-risk (HR 0.77 [0.52-1.15], p=0.2) or intermediate-risk (HR 0.90 [0.55-1.48], p=0.7) NMIBC. Subgroup analysis suggested that time to recurrence was longer in pT1 NMIBC patients treated with celecoxib compared with those receiving placebo (HR 0.53 [0.30-0.94], interaction test p=0.04). The 3-yr progression rates in high-risk patients were low: 10% (6.5-17%) and 9.7% (6.0-15%) in celecoxib and placebo arms, respectively. Incidence of serious cardiovascular events was higher in celecoxib (5.2%) than in placebo (1.7%) group (difference +3.4% [-0.3% to 7.2%], p=0.07). CONCLUSIONS: BOXIT did not show that celecoxib reduces the risk of recurrence in intermediate- or high-risk NMIBC, although celecoxib was associated with delayed time to recurrence in pT1 NMIBC patients. The increased risk of cardiovascular events does not support the use of celecoxib. PATIENT SUMMARY: Celecoxib was not shown to reduce the risk of recurrence in intermediate- or high-risk non-muscle-invasive bladder cancer (NMIBC), although celecoxib was associated with delayed time to recurrence in pT1 NMIBC patients. The increased risk of cardiovascular events does not support the use of celecoxib.

Radiofrequency-induced Thermo-chemotherapy Effect Versus a Second Course of Bacillus Calmette-Guérin or Institutional Standard in Patients with Recurrence of Non-muscle-invasive Bladder Cancer Following Induction or Maintenance Bacillus Calmette-Guérin Therapy (HYMN): A Phase III, Open-label, Randomised Controlled Trial.

BACKGROUND: There is no effective intravesical second-line therapy for non-muscle-invasive bladder cancer (NMIBC) when bacillus Calmette-Guérin (BCG) fails. OBJECTIVE: To compare disease-free survival time (DFS) between radiofrequency-induced thermo-chemotherapy effect (RITE) and institutional standard second-line therapy (control) in NMIBC patients with recurrence following induction/maintenance BCG. DESIGN, SETTINGS, AND PARTICIPANTS: Open-label, phase III randomised controlled trial accrued across 14 centres between May 2010 and July 2013 (HYMN [ClinicalTrials.gov: NCT01094964]). INTERVENTION: Patients were randomly assigned (1:1) to RITE (60min, 40mg mitomycin-C, 42±2°C) or control following stratification for carcinoma in situ (CIS) status (present/absent), therapy history (failure of previous induction/maintenance BCG), and treatment centre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome measures were DFS and complete response (CR) at 3 mo for the CIS at randomisation subgroup. Analysis was based on intention-to-treat. RESULTS AND LIMITATIONS: A total of 104 patients were randomised (48 RITE: 56 control). Median follow-up for the 31 patients without a DFS event was 36 mo. There was no significant difference in DFS between treatment arms (hazard ratio [HR] 1.33, 95% confidence interval [CI] 0.84-2.10, p=0.23) or in 3-mo CR rate in CIS patients (n=71; RITE: 30% vs control: 47%, p=0.15). There was no significant difference in DFS between treatment arms in non-CIS patients (n=33; RITE: 53% vs control: 24% at 24 mo, HR 0.50, 95% CI 0.22-1.17, p=0.11). DFS was significantly lower in RITE than in control in CIS with/without papillary patients (n=71; HR 2.06, 95% CI 1.17-3.62, p=0.01; treatment-subgroup interaction p=0.007). Disease progression was observed in four patients in each treatment arm. Adverse events and health-related quality of life between treatment arms were comparable. CONCLUSIONS: DFS was similar between RITE and control. RITE may be a second-line therapy for non-CIS recurrence following BCG failure; however, confirmatory trials are needed. RITE patients with CIS with/without papillary had lower DFS than control. HYMN highlights the importance of the control arm when evaluating novel therapies. PATIENT SUMMARY: This study did not show a difference in bladder cancer outcomes between microwave-heated chemotherapy and standard of care treatment. Papillary bladder lesions may benefit from microwave-heated chemotherapy treatment; however, more research is needed. Both treatments are similarly well tolerated.

Prognostic significance of tumor hypoxia inducible factor-1alpha expression for outcome after radiotherapy in oropharyngeal cancer.

PURPOSE: Head-and-neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of patients in terms of subsite, treatment, and biology. Currently most management decisions are based on clinical parameters with little appreciation of patient differences in underlying tumor biology. We investigated the prognostic significance of clinicopathologic features and tumor hypoxia-inducible factor-1alpha (HIF-1alpha) expression in a homogeneous series of patients who underwent radiotherapy. METHODS AND MATERIALS: An audit identified 133 consecutive patients with histologically proven squamous cell carcinoma of the tonsil or tongue base. All patients received primary radiotherapy between 1996 and 2001. Tumor HIF-1alpha expression was examined in 79 patients. RESULTS: Features associated with poor locoregional control were low Hb level (p = 0.05) and advancing T (p = 0.008), N (p = 0.03), and disease (p = 0.008) stage. HIF-1alpha expression was a more significant adverse prognostic factor in the tonsil (hazard ratio [HR], 23.1; 95% confidence interval [CI]. 3.04-176.7) than the tongue-base tumor (HR, 2.86; 95% CI, 1.14-7.19) group (p = 0.03, test for interaction). High tumor HIF-1alpha expression was associated with low blood Hb levels (p = 0.03). In a multivariate analysis HIF-1alpha expression retained prognostic significance for locoregional control (HR, 7.10; 95% CI, 3.07-16.43) and cancer-specific survival (HR, 9.19; 95% CI, 3.90-21.6). CONCLUSIONS: There are significant differences in radiation therapy outcome within a homogeneous subsite of the oropharynx related to molecular marker expression. The work highlights the importance of studying homogeneous groups of patients in HNSCC, and the complex interrelationships between tumor biology and clinicopathologic factors. The establishment of tumor-type specific markers would represent a major advance in this area.