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.

Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial.

BACKGROUND: The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression. METHODS: We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7-10, positive margins, or preoperative PSA ≥10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA ≥0·1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52·5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047. FINDINGS: Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60-68). Median follow-up was 4·9 years (IQR 3·0-6·1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1·10, 95% CI 0·81-1·49; p=0·56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0·88, 95% CI 0·58-1·33; p=0·53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4·8 vs 4·0; p=0·0023). Grade 3-4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0·020). INTERPRETATION: These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy. FUNDING: Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society.

Diethylstilboestrol (1 mg) in the management of castration-resistant prostate cancer.

OBJECTIVE: To investigate the efficacy of diethylstilboestrol (DES) in patients with advanced prostate cancer refractory to androgen suppression. METHODS: This retrospective study comprises 194 patients with prostate cancer treated with DES (1 mg daily) between 1976 and 2010. Study outcome parameters included demographic data, tumour characteristics, treatment history, prostate-specific antigen (PSA) responses, radiologic studies, adverse events and overall survival. RESULTS: At initiation of oestrogen therapy the mean patient age was 69 years (range: 48-89) and the median PSA was 96 ng/ml (range: 1.9-9,500). The median duration of prior prostate cancer treatment was 29 months (range: 1-365). DES was the second-line treatment in 58 patients and the third/fourth-line therapy in 136 men. A formal (≥50%) PSA response was observed in 95 patients (48.9%) and the median time to progression (TTP) was 250 days (95% CI, 180-360) for this group. An additional 62 patients (31.9%) had a partial PSA response with a median TTP of 150 days (95% CI, 92-180). Thirty-seven patients (19.1%) did not have a PSA response and the median TTP was 90 days (95% CI, 90-97). The median overall survival from the start of oestrogen therapy for the entire cohort was 576 days (95% CI, 482-690). The median overall survival of patients who had a formal (≥50%), partial (<50%) and no PSA response was 756 (95% CI, 670-1,429), 428 (95% CI, 340-630) and 329 (95% CI, 287-510) days, respectively. Thirty-nine patients (20.1%) were still alive at the end of the study. No treatment-related deaths occurred. CONCLUSIONS: In the age of chemotherapy this study highlights the efficacy of oestrogen therapy in castration-refractory prostate cancer. The optimal point in the therapeutic pathway at which DES should be prescribed remains to be established.

Routine urethroscopic surveillance is of limited value after radical cystectomy: a single centre retrospective cohort analysis.

PURPOSE: The incidence of urethral recurrence (UR) following radical cystectomy (RC) for transitional cell carcinoma (TCC) of the bladder varies between 1.5 and 6%. There is debate over the timing of urethrectomy for patients undergoing RC. We evaluated the requirement for a formal surveillance programme for UR in patients after RC. METHODS: We retrospectively reviewed the outcomes of patients who underwent RC between 2006 and 2019. Females, non-TCC cases and patients with neo-bladder diversions were excluded. Histological prostatic urethral involvement at the time of RC was deemed high risk for UR. Carcinoma in-situ, multifocal tumours and bladder neck involvement were deemed intermediate risk and the absence of the above features was considered low risk. RESULTS: 417 patients underwent RC, 300 cases remained after exclusion criteria were applied. 42 patients were high-risk for UR, 102 patients were intermediate risk and 156 were low risk. Of the 300, 24 urethrectomy cases were recorded. Six cases of UR occurred. Of these, 5 presented with symptoms and only 1 case was detected by surveillance. Only 1 low-risk patient developed UR, 7 years post RC. Using our risk stratification, UR rates for high, intermediate and low-risk cohorts were 25%, 10.5% and 0.8%, respectively. CONCLUSIONS: In our cohort, routine surveillance for all patients with annual urethroscopy was of limited value in detecting UR post RC. Staged Urethrectomy for high and intermediate-risk patients, and patient counselling in self-identification of recurrence symptoms for low-risk patients will improve the early detection of UR.

Iatrogenic splenectomy during left nephrectomy: a single-institution experience of eight years.

INTRODUCTION: Iatrogenic injury to the spleen is not an uncommon complication. Left nephrectomy has been reported as the second commonest cause of iatrogenic splenectomy with a reported incidence between 1.3 and 24%. Iatrogenic splenectomy is associated with significant morbidity and mortality. AIMS: We reviewed the occurrence of iatrogenic splenectomy during left nephrectomy at our centre. Our aims were to determine the incidence of iatrogenic splenectomy within the Mid Yorkshire Hospitals NHS Trust in order to understand the nature of the splenic injury and the morbidity and mortality associated with it. METHODS: All splenectomy and nephrectomy histology reports from January 2000 to December 2007 were reviewed retrospectively. Indications for splenectomy and nephrectomy were identified. Patients' demographic data, tumour characteristics, operative details, length of hospital stay and any reported morbidity or mortality were collected. RESULTS: A total of 447 nephrectomies were identified which included 234 left nephrectomies. Within the same period 136 cases of splenectomy were performed. Thirty-four cases were iatrogenic splenectomies and 12 were caused by left nephrectomy. The incidence was 5.13%. The male to female ratio was 1:1 with an average age of 66 years. Grade 2 and stage pT2 renal cancer were the commonest tumour characteristics. All iatrogenic injuries occurred during mobilisation of the colon or division of adhesion. The average operative time was 4.7 h. Average length of hospital stay was 14 days. Five patients had postoperative complications and 1 died of respiratory failure and sepsis. CONCLUSION: Splenic injury during left nephrectomy is a morbid complication. A good understanding of anatomy and surgical approach may reduce the incidence, morbidity and mortality of iatrogenic splenectomy during left nephrectomy.

Radical Cystectomy Against Intravesical BCG for High-Risk High-Grade Nonmuscle Invasive Bladder Cancer: Results From the Randomized Controlled BRAVO-Feasibility Study.

PURPOSE: High-grade nonmuscle invasive bladder cancer (HRNMIBC) is a heterogeneous disease. Treatments include intravesical maintenance Bacillus Calmette-Guerin (mBCG) and radical cystectomy (RC). We wanted to understand whether a randomized trial comparing these options was possible. MATERIALS AND METHODS: We conducted a two-arm, prospective multicenter randomized study to determine the feasibility in Bacillus Calmette-Guerin-naive patients. Participants had new high-risk HRNMIBC suitable for both treatments. Random assignment was stratified by age, sex, center, stage, presence of carcinoma in situ, and prior low-risk bladder cancer. Qualitative work investigated how to maintain equipoise. The primary outcome was the number of patients screened, eligible, recruited, and randomly assigned. RESULTS: We screened 407 patients, approached 185, and obtained consent from 51 (27.6%) patients. Of these, one did not proceed and therefore 50 were randomly assigned (1:1). In the mBCG arm, 23/25 (92.0%) patients received mBCG, four had nonmuscle invasive bladder cancer (NMIBC) after induction, three had NMIBC at 4 months, and four received RC. At closure, two patients had metastatic BC. In the RC arm, 20 (80.0%) participants received cystectomy, including five (25.0%) with no tumor, 13 (65.0%) with HRNMIBC, and two (10.0%) with muscle invasion in their specimen. At follow-up, all patients in the RC arm were free of disease. Adverse events were mostly mild and equally distributed (15/23 [65.2%] patients with mBCG and 13/20 [65.0%] patients with RC). The quality of life (QOL) of both arms was broadly similar at 12 months. CONCLUSION: A randomized controlled trial comparing mBCG and RC will be challenging to recruit into. Around 10% of patients with high-risk HRNMIBC have a lethal disease and may be better treated by primary radical treatment. Conversely, many are suitable for bladder preservation and may maintain their prediagnosis QOL.

Fulguration of the lumen does not improve vasectomy sterilization rates.

OBJECTIVES: To assess the effect of adding lumen diathermy fulguration to our standard technique of vas ligation with polyglactin 910 (Vicryl(TM), Ethicon, Sommerville, NJ, USA) excision and fascial interposition, in an attempt to improve our sterilization rates. We previously reported the effect of changing suture material on vasectomy success rates; 3005 post-vasectomy semen analyses (PVSA) revealed a decrease in sterilization rates after surgery on changing from chromic catgut to polyglactin 910. PATIENTS AND METHODS: We retrospectively reviewed PVSA undertaken for vasectomies performed by urological surgeons at the Mid-Yorkshire NHS Trust for 18 months from September 2005 to February 2007. RESULTS: There were 592 vasectomies in all; the age distribution of patients between the groups treated with the standard and new method was similar. Overall, 166 patients (28%) failed to provide two semen samples as instructed, and so were excluded from further analyses. Sterility was achieved in 367 patients (86%); a further 28 (7%) have indeterminate analyses to date, with one of the last two PVSAs showing sperm, with the PVSA of 32 (7%) patients showing persisting sperm. For the eight surgeons reviewed the sterility rates were broadly similar. CONCLUSIONS: The introduction of diathermy fulguration of the lumen has not improved vasectomy sterilization rates, with up to 14% having sperm on PVSA.

Radical cystectomy (bladder removal) against intravesical BCG immunotherapy for high-risk non-muscle invasive bladder cancer (BRAVO): a protocol for a randomised controlled feasibility study.

INTRODUCTION: High-risk non-muscle invasive bladder cancer (HRNMIBC) is a heterogeneous disease that can be difficult to predict. While around 25% of cancers progress to invasion and metastases, the remaining majority of tumours remain within the bladder. It is uncertain whether patients with HRNMIBC are better treated with intravesical maintenance BCG (mBCG) immunotherapy or primary radical cystectomy (RC). A definitive randomised controlled trial (RCT) is needed to compare these two different treatments but may be difficult to recruit to and has not been attempted to date. Before undertaking such an RCT, it is important to understand whether such a comparison is possible and how best to achieve it. METHODS AND ANALYSIS: BRAVO is a multi-centre, parallel-group, mixed-methods, individually randomised, controlled, feasibility study for patients with HRNMIBC. Participants will be randomised to receive either mBCG immunotherapy or RC. The primary objective is to assess the feasibility and acceptability of performing the definitive phase III trial via estimation of eligibility and recruitment rates, assessing uptake of allocated treatment and compliance with mBCG, determining quality-of-life questionnaire completion rates and exploring reasons expressed by patients for declining recruitment into the study. We aim to recruit 60 participants from six centres in the UK. Surgical trials with disparate treatment options find recruitment challenging from both the patient and clinician perspective. By building on the experiences of other similar trials through implementing a comprehensive training package aimed at clinicians to address these challenges (qualitative substudy), we hope that we can demonstrate that a phase III trial is feasible. ETHICS AND DISSEMINATION: The study has ethical approval (16/YH/0268). Findings will be made available to patients, clinicians, the funders and the National Health Service through traditional publishing and social media. TRIAL REGISTRATION NUMBER: ISRCTN12509361; Pre results.

A complex caliceal-cutaneous and caliceal-peritoneal fistula in a renal transplant patient: a case for conservative management.

Caliceal fistula is a rare complication after renal transplant and may lead to graft failure. We present a case of complex caliceal-cutaneous and caliceal-peritoneal fistula in a renal transplant patient who was successfully managed conservatively.

A 10-year retrospective review of a nonrandomized cohort of 458 patients undergoing radical radiotherapy or cystectomy in Yorkshire, UK.

PURPOSE: We have previously reported on the mortality, morbidity, and 5-year survival of 458 patients who underwent radical radiotherapy or surgery for invasive bladder cancer in Yorkshire from 1993 to 1996. We aim to present the 10-year outcomes of these patients and to reassess factors predicting survival. METHODS AND MATERIALS: The Northern and Yorkshire Cancer Registry identified 458 patients whose cases were subjected to Kaplan-Meier all-cause survival analyses, and a retrospective casenote analysis was undertaken on 398 (87%) for univariate and multivariate Cox proportional hazards modeling. Additional proportional hazards regression modeling was used to assess the statistical significance of variables on overall survival. RESULTS: The ratio of radiotherapy to cystectomy was 3:1. There was no significant difference in overall 10-year survival between those who underwent radiotherapy (22%) and radical cystectomy (24%). Univariate analyses suggested that female sex, performance status, hydronephrosis and clinical T stage, were associated with an inferior outcome at 10 years. Patient age, tumor grade, treatment delay, and caseload factors were not significant. Multivariate analysis models were created for 0-2 and 2-10 years after treatment. There were no significant differences in treatment for 0-2 years; however, after 2 years follow-up there was some evidence of increased survival for patients receiving surgery compared with radiotherapy (hazard ratio 0.66, 95% confidence interval: 0.44-1.01, p = 0.06). CONCLUSIONS: a 10-year minimum follow-up has rarely been reported after radical treatment for invasive bladder cancer. At 10 years, there was no statistical difference in all-cause survival between surgery and radiotherapy treatment modalities.