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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.

Transurethral resection of bladder tumours (TURBT) using a wire loop remains the gold-standard treatment for bladder tumours, but it is associated with unacceptably high early recurrence rates after first resection. Improvements to standard resection techniques and a range of optical and technological advances offer exciting possibilities for improving outcomes. Early second resection has been shown to reduce recurrence rates, and increase response to intravesical chemotherapy and/or immunotherapy. It should be considered in most high-risk non-muscle invasive cancers (T1; G3; multifocal) being managed by bladder conservation. Newer energy sources, such as laser, may facilitate day case management of bladder tumours using local anaesthesia in select groups of patients. The novel technique of photodynamic diagnosis improves tumour detection, and quality of resection, and is likely to become the standard for initial tumour management. The traditional 'incise and scatter' resection technique goes against all oncological surgical principles. En-bloc resection of tumours would be far preferable and demands further development and evaluation. The technique of TURBT needs to evolve to allow first-time clearance of disease and low recurrence rates.

and then using HAL-FC. The main outcome was the frequency and nature of additional pathology detected by HAL-FC. Twentyseven patients (21 men and six women; median age 70 years, range 49-82) underwent 32 HAL-FC. RESULTSRecurrent 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 falsepositive 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. CONCLUSIONSClinically 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.

'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. RESULTSTwenty-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. CONCLUSIONAdditional 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.

with Von Hippel-Lindau (VHL) disease. In all, 21 OPNs were in the context of a single kidney. RESULTSIn all, 95 OPNs were successfully completed; one operation was abandoned and there were four nephrectomies, including two for bleeding, one for a positive margin on frozensection analysis, and one for multifocal tumours. The median warm/cold ischaemia time was 20/33 min. The intraoperative/early complication rate was 36%, including a major complication rate of 11% and re-operation rate for primary bleeding of 3%. Of 36 complications, 30 (83%) were in 23 patients with either an imperative indication or VHL. Complications were more common in the imperative/VHL group (59%) than in the elective/other group (12%). Renal function was preserved in 80 of 100 (80%) OPNs overall. Creatinine levels returned to baseline in 11 of 21 (50%) patients with renal impairment before OPN and in 12 of 20 (60%) with a single kidney, whilst five of 21 (24%) with a single kidney needed dialysis after OPN. The median (range) stay after surgery was 6 (3-50) nights. A malignant diagnosis was confirmed in 76 of 93 (82%) specimens on final histopathology. There were 11 of 100 (11%) positive margins, one managed by immediate conversion to nephrectomy and the remaining 10 managed expectantly. After a median (range) follow-up of 24 (1-69) months there were no deaths from kidney cancer, but three patients had local recurrences and two others had developed metastatic recurrence. CONCLUSIONOPN is complex surgery, especially in the imperative setting, but very good results are achievable outside established centres of world renown. It provides good cancer control in the short term with low renal morbidity. These results may act as a reference point in the UK by which to compare results of new treatments for kidney cancer.

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