A Randomized Trial of PHOTOdynamic Surgery in Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: Recurrence of non­muscle-invasive bladder cancer (NMIBC) is common after transurethral resection of bladder tumor (TURBT). Photodynamic diagnosis (PDD) provides better diagnostic accuracy and more complete tumor resection and may reduce recurrence. However, there is limited evidence on the longer-term clinical effectiveness and cost-effectiveness of PDD-guided resection. METHODS: In this pragmatic, open-label, parallel-group randomized trial conducted in 22 U.K. National Health Service hospitals, we recruited participants with a suspected first diagnosis of NMIBC at intermediate or high risk for recurrence on the basis of routine visual assessment before being listed for TURBT. Participants were assigned (1:1) to PDD-guided TURBT or to standard white light (WL)­guided TURBT. The primary clinical outcome was time to recurrence at 3 years of follow-up, analyzed by modified intention to treat. RESULTS: A total of 538 participants were enrolled (269 in each group), and 112 participants without histologic confirmation of NMIBC or who had had cystectomy were excluded. After 44 months' median follow-up, 86 of 209 in the PDD group and 84 of 217 in the WL group had recurrences. The hazard ratio for recurrence was 0.94 (95% confidence interval [CI], 0.69 to 1.28; P=0.70). Three-year recurrence-free rates were 57.8% (95% CI, 50.7 to 64.2) and 61.6% (95% CI, 54.7 to 67.8) in the PDD and WL groups, respectively, with an absolute difference of −3.8 percentage points (95% CI, −13.37 to 5.59) favoring PDD. Adverse events occurred in less than 2% of participants, and rates were similar in both groups, as was health-related quality of life. PDD-guided TURBT was £876 (95% CI, −766 to 2518; P=0.591) more costly than WL-guided TURBT over a 3-year follow-up, with no evidence of a difference in quality-adjusted life years (−0.007; 95% CI, −0.133 to 0.119; P=0.444). CONCLUSIONS: PDD-guided TURBT did not reduce recurrence rates, nor was it cost-effective compared with WL at 3 years. (Funded by the National Institute for Health and Care Research Health Technology Assessment program; ISRCTN number, ISRCTN84013636.)

Open urethroplasty versus endoscopic urethrotomy for recurrent urethral stricture in men: the OPEN RCT.

BACKGROUND: Men who suffer recurrence of bulbar urethral stricture have to decide between endoscopic urethrotomy and open urethroplasty to manage their urinary symptoms. Evidence of relative clinical effectiveness and cost-effectiveness is lacking. OBJECTIVES: To assess benefit, harms and cost-effectiveness of open urethroplasty compared with endoscopic urethrotomy as treatment for recurrent urethral stricture in men. DESIGN: Parallel-group, open-label, patient-randomised trial of allocated intervention with 6-monthly follow-ups over 24 months. Target sample size was 210 participants providing outcome data. Participants, clinicians and local research staff could not be blinded to allocation. Central trial staff were blinded when needed. SETTING: UK NHS with recruitment from 38 hospital sites. PARTICIPANTS: A total of 222 men requiring operative treatment for recurrence of bulbar urethral stricture who had received at least one previous intervention for stricture. INTERVENTIONS: A centralised randomisation system using random blocks allocated participants 1 : 1 to open urethroplasty (experimental group) or endoscopic urethrotomy (control group). MAIN OUTCOME MEASURES: The primary clinical outcome was control of urinary symptoms. Cost-effectiveness was assessed by cost per quality-adjusted life-year (QALY) gained over 24 months. The main secondary outcome was the need for reintervention for stricture recurrence. RESULTS: The mean difference in the area under the curve of repeated measurement of voiding symptoms scored from 0 (no symptoms) to 24 (severe symptoms) between the two groups was -0.36 [95% confidence interval (CI) -1.78 to 1.02; p = 0.6]. Mean voiding symptom scores improved between baseline and 24 months after randomisation from 13.4 [standard deviation (SD) 4.5] to 6 (SD 5.5) for urethroplasty group and from 13.2 (SD 4.7) to 6.4 (SD 5.3) for urethrotomy. Reintervention was less frequent and occurred earlier in the urethroplasty group (hazard ratio 0.52, 95% CI 0.31 to 0.89; p = 0.02). There were two postoperative complications requiring reinterventions in the group that received urethroplasty and five, including one death from pulmonary embolism, in the group that received urethrotomy. Over 24 months, urethroplasty cost on average more than urethrotomy (cost difference £2148, 95% CI £689 to £3606) and resulted in a similar number of QALYs (QALY difference -0.01, 95% CI -0.17 to 0.14). Therefore, based on current evidence, urethrotomy is considered to be cost-effective. LIMITATIONS: We were able to include only 69 (63%) of the 109 men allocated to urethroplasty and 90 (80%) of the 113 men allocated to urethrotomy in the primary complete-case intention-to-treat analysis. CONCLUSIONS: The similar magnitude of symptom improvement seen for the two procedures over 24 months of follow-up shows that both provide effective symptom control. The lower likelihood of further intervention favours urethroplasty, but this had a higher cost over the 24 months of follow-up and was unlikely to be considered cost-effective. FUTURE WORK: Formulate methods to incorporate short-term disutility data into cost-effectiveness analysis. Survey pathways of care for men with urethral stricture, including the use of enhanced recovery after urethroplasty. Establish a pragmatic follow-up schedule to allow national audit of outcomes following urethral surgery with linkage to NHS Hospital Episode Statistics. TRIAL REGISTRATION: Current Controlled Trials ISRCTN98009168. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 61. See the NIHR Journals Library website for further project information.

The urethra carries urine from the bladder to the tip of the penis. Men can develop a condition called urethral stricture when part of the urethra narrows due to scarring. This can lead to difficulties in passing urine and can recur. There are two operations for urethral stricture. The standard approach is endoscopic urethrotomy. The alternative is open urethroplasty. This study wanted to find out which operation was preferable in terms of symptom control, time before further surgery and which operation was best value for the NHS. All aspects of the study were informed by patients. Two hundred and twenty-two men who had received at least one previous operation for stricture took part. The choice of operation was decided by chance (randomisation). Of these men, 113 were randomised to urethrotomy and 109 were randomised to urethroplasty. Following their operation, the men filled in questionnaires every 3­6 months for 2 years about their symptoms and if any further surgery was needed. The two groups were then compared. Of the 222 men who took part, 159 provided enough information for inclusion in the comparison (90 were in the urethrotomy group and 69 were in the urethroplasty group). The improvement over time in urinary symptoms was similar for the two groups. Men in the urethrotomy group were twice as likely to need a further operation over the 2-year study period. Very few men experienced serious complications. This study showed that both operations led to symptom improvement for men with recurrent urethral stricture. Urethroplasty, however, appears unlikely to offer good value for money for the NHS. Men needing treatment for recurrent urethral stricture can use this information to weigh up the pros and cons of each operation to decide with their clinical team which one to undergo.

Surgical Treatment for Recurrent Bulbar Urethral Stricture: A Randomised Open-label Superiority Trial of Open Urethroplasty Versus Endoscopic Urethrotomy (the OPEN Trial).

BACKGROUND: Urethral stricture affects 0.9% of men. Initial treatment is urethrotomy. Approximately, half of the strictures recur within 4 yr. Options for further treatment are repeat urethrotomy or open urethroplasty. OBJECTIVE: To compare the effectiveness and cost-effectiveness of urethrotomy with open urethroplasty in adult men with recurrent bulbar urethral stricture. DESIGN, SETTING, AND PARTICIPANTS: This was an open label, two-arm, patient-randomised controlled trial. UK National Health Service hospitals were recruited and 222 men were randomised to receive urethroplasty or urethrotomy. INTERVENTION: Urethrotomy is a minimally invasive technique whereby the narrowed area is progressively widened by cutting the scar tissue with a steel blade mounted on a urethroscope. Urethroplasty is a more invasive surgery to reconstruct the narrowed area. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the profile over 24 mo of a patient-reported outcome measure, the voiding symptom score. The main clinical outcome was time until reintervention. RESULTS AND LIMITATIONS: The primary analysis included 69 (63%) and 90 (81%) of those allocated to urethroplasty and urethrotomy, respectively. The mean difference between the urethroplasty and urethrotomy groups was -0.36 (95% confidence interval [CI] -1.74 to 1.02). Fifteen men allocated to urethroplasty needed a reintervention compared with 29 allocated to urethrotomy (hazard ratio [95% CI] 0.52 [0.31-0.89]). CONCLUSIONS: In men with recurrent bulbar urethral stricture, both urethroplasty and urethrotomy improved voiding symptoms. The benefit lasted longer for urethroplasty. PATIENT SUMMARY: There was uncertainty about the best treatment for men with recurrent bulbar urethral stricture. We randomised men to receive one of the following two treatment options: urethrotomy and urethroplasty. At the end of the study, both treatments resulted in similar and better symptom scores. However, the urethroplasty group had fewer reinterventions.