title: Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial.
abstract: BACKGROUND
  Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial.
  
  
  METHODS
  This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov, number NCT01310894.
  
  
  RESULTS
  Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24-25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0·34, 95% CI 0·24-0·46; p<0·0001). 101 (49%) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 (14%) men in the active surveillance group (adjusted risk ratio 3·67, 95% CI 2·53-5·33; p<0·0001). Vascular-targeted photodynamic therapy was well tolerated. The most common grade 3-4 adverse events were prostatitis (three [2%] in the vascular-targeted photodynamic therapy group vs one [<1%] in the active surveillance group), acute urinary retention (three [2%] vs one [<1%]) and erectile dysfunction (two [1%] vs three [1%]). The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine (15 patients; severe in three); this event resolved within 2 months in all patients. The most common serious adverse event in the active surveillance group was myocardial infarction (three patients).
  
  
  CONCLUSIONS
  Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy.
  
  
  BACKGROUND
  Steba Biotech.
authors.affiliation: Department of Urology, Angers University Hospital, Angers, France.
authors.forename: Abdel-Rahmène
authors.initials: AR
authors.lastname: Azzouzi
authors.affiliation: Department of Urology, CIC-INSERM 1414, Rennes University Hospital, Rennes, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Vincendeau
authors.affiliation: Department of Urology, Institut Montsouris, Université Paris Descartes, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Barret
authors.affiliation: Department of Urology, Centre Catalan Urologie Andrologie, Cabestany, France.
authors.forename: Antony
authors.initials: A
authors.lastname: Cicco
authors.affiliation: Department of Urology, Besançon University Hospital, Besançon, France.
authors.forename: François
authors.initials: F
authors.lastname: Kleinclauss
authors.affiliation: Department of Urology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands.
authors.forename: Henk G
authors.initials: HG
authors.lastname: van der Poel
authors.affiliation: Department of Urology, LMU-Klinikum der Universität München, Munich, Germany.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Stief
authors.affiliation: Department of Urology, SLK Kliniken, Heilbronn, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Rassweiler
authors.affiliation: Martini-Clinic Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Salomon
authors.affiliation: Department of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Solsona
authors.affiliation: Department of Urology, Hospital Clinic, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Alcaraz
authors.affiliation: Department of Urology, Tampere University Hospital and School of Medicine, Tampere, Finland.
authors.forename: Teuvo T
authors.initials: TT
authors.lastname: Tammela
authors.affiliation: Academic Department of Urology, University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Rosario
authors.affiliation: Department of Urology, Salamanca University Hospital GITUR-IBSAL, Salamanca, Spain; Department of Urology, University Hospital Complex, La Coruna, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Gomez-Veiga
authors.affiliation: Department of Urology, Skäne University Hospital, Malmö, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Ahlgren
authors.affiliation: Medical Department, Steba Biotech, Paris, France.
authors.forename: Fawzi
authors.initials: F
authors.lastname: Benzaghou
authors.affiliation: Medical Department, Steba Biotech, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Gaillac
authors.affiliation: LA-SER Analytica, London, UK.
authors.forename: Billy
authors.initials: B
authors.lastname: Amzal
authors.affiliation: Andros Men's Health Institute, Arnhem, Netherlands.
authors.forename: Frans M J
authors.initials: FM
authors.lastname: Debruyne
authors.affiliation: Department of Pathology, Tours University Hospital, Tours, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Fromont
authors.affiliation: Department of Urology, LMU-Klinikum der Universität München, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gratzke
authors.affiliation: Division of Surgery and Interventional Science, University College London, London, UK. Electronic address: m.emberton@ucl.ac.uk.
authors.forename: Mark
authors.initials: M
authors.lastname: Emberton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001429:Bacteriochlorophylls / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011159:Population Surveillance; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018570:Risk Assessment; D015996:Survival Rate
chemical_list: D001429:Bacteriochlorophylls; D017319:Photosensitizing Agents; C503696:padeliporfin