title: Photodynamic therapy for superficial bladder cancer under local anaesthetic.
abstract: OBJECTIVE
  To evaluate the use of local anaesthesia (LA) in 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) for superficial transitional cell carcinoma (TCC) of the bladder, and to provide further toxicity and tolerability data on this new method within the context of a phase 1 trial.
  
  
  METHODS
  ALA PDT was administered to 19 patients with recurrent superficial TCC (stage Ta/carcinoma in situ, grades 1-3) using escalating doses of ALA (3-6%) and 633 nm laser light (25-50 J/cm2) under various LA (lignocaine) protocols. Pain was assessed using a linear analogue scale from 0 to 10. The endpoints of tolerability and toxicity were assessed for the different LA, light and ALA doses, with lignocaine levels.
  
  
  RESULTS
  ALA PDT is painful and requires some form of anaesthesia. The discomfort was immediate, associated with bladder spasm, and was a function of the ALA concentration rather than the total light dose given. Simple passive diffusion (PD) of 2% lignocaine instilled for 40 min before PDT gave adequate anaesthesia with 3% ALA (n=8; median pain score 1, range 0-2). With 6% ALA the pain was dramatically increased using PD (n=6; median pain score 8, range 5-10) and therefore the more potent LA technique of electromotive drug administration (EMDA) of 2% lignocaine was used, with excellent results (n=3; median pain score 1, range 0-2). All patients had transient bladder irritability that typically lasted 9-12 days, with no subjective/objective change in long-term bladder function. No other toxicity was reported. Serum lignocaine levels were minimal.
  
  
  CONCLUSIONS
  Bladder ALA PDT is both safe and feasible under LA. At a dose of 3% ALA, the procedure was well-tolerated using PD of lignocaine. At higher doses (6% ALA) more effective anaesthesia is required and this can be obtained satisfactorily with EMDA of lignocaine. With refinement, ALA PDT may be feasible as an outpatient treatment for superficial bladder TCC.
authors.affiliation: Department of Urology, Hope Hospital, Salford Royal Hospitals Trust, Salford, UK. daveshackley@hotmail.com
authors.forename: D C
authors.initials: DC
authors.lastname: Shackley
authors.forename: C
authors.initials: C
authors.lastname: Briggs
authors.forename: A
authors.initials: A
authors.lastname: Gilhooley
authors.forename: C
authors.initials: C
authors.lastname: Whitehurst
authors.forename: K J
authors.initials: KJ
authors.lastname: O'Flynn
authors.forename: C D
authors.initials: CD
authors.lastname: Betts
authors.forename: J V
authors.initials: JV
authors.lastname: Moore
authors.forename: N W
authors.initials: NW
authors.lastname: Clarke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D000772:Anesthesia, Local; D000779:Anesthetics, Local; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008012:Lidocaine; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010146:Pain / Q000517:prevention & control; D010147:Pain Measurement; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D000779:Anesthetics, Local; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; D008012:Lidocaine