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

Abstract

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.

EAU Guidelines on Non–Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016

“…A meta-analysis reported an increase in detection of tumour lesions in HAL arms and an absolute reduction < 10% in recurrence rates within 12 mo [47] (LE: 1a). The beneficial effect of HAL FC on recurrence rates in patients with TURB and early intravesical instillation of chemotherapy was not confirmed by prospective randomised trials [48]. The value of FC for improvement of outcome in relation to progression rate and survival remains to be demonstrated.…”

Contemporary cost-consequence analysis of blue light cystoscopy with hexaminolevulinate in non-muscle-invasive bladder cancer

“…[13][14][15][16][17][18][19][20][21][22] Systematic reviews and meta-analyses have concluded that BLC with HAL improves recurrence rates, particularly in patients with high-risk bladder tumours.…”

“…Among these 33 studies were 10 RCTs of BLC with HAL vs. WLC that were used to meta-analyze sensitivities and specificities. [13][14][15][16][17][18][19][20][21][22] Burger et al recently used raw data of RCTs to metaanalyze recurrence relative risk (RR) for BLC with HAL vs. WLC-assisted TURBT, and this RR (0.761) was used in the baseline decision-tree analysis. 23 …”

“…Input probabilities were calculated from meta-analysis of the existing literature for sensitivities, specificities, and recurrence probabilities. [13][14][15][16][17][18][19][20][21][22] As mentioned, the previous meta-analyzed RR for recurrence was used (0.761; 95% confidence interval [CI] 0.627-0.924). 23 Provincial base outcomes were assessed, including: initial cost, followup cost, five-year amortized cost, cost-difference per case, bed day use, and recurrences.…”

Promises and challenges of fluorescence cystoscopy

“…In multivariable analysis, performances of HAL-TURBT, pathologic tumor, and nodal stage as well as soft tissue surgical margin status were independent predictors for recurrence-free survival as well as cancer-specific survival but there are significant biases associated with retrospective studies and this would have to be validated. There is also a prospective randomized trial of HAL-BLC plus single-shot intravesical mitomycin C vs. standard TURBT plus singleshot intravesical mitomycin C that found no significant difference in recurrence between the two arms at 3 or 12 months [13]. Although this study suggests that postoperative intravesical chemotherapy may negate the benefits of BLC, there were some differences between the groups with respect to administration of postoperative MMC (63% HAL vs. 77% WL) and aggressiveness of disease (secondary CIS: 26% HAL vs. 14% WL) that could affect the outcomes.…”