title: A phase I trial of pre-operative radiotherapy for prostate cancer: clinical and translational studies.
abstract: OBJECTIVE
  Selected patients undergoing radical prostatectomy for localized prostate cancer can be at high-risk for pT3 disease and require subsequent radiotherapy. In a phase I trial, we investigated the feasibility of pre-operative radiotherapy for this patient subset.
  
  
  METHODS
  Eligibility criteria were: T1/T2N0M0 tumors plus (i) Gleason >or=7, PSA>10 ng/ml and <35 ng/ml, or (ii), PSA >15 ng/ml and less <35 ng/ml (any Gleason). Patients received 25 Gy in five fractions of radiotherapy followed by radical prostatectomy. Trial endpoints included intra-operative morbidity and late toxicity following combined treatment. We also stained pre- and post-radiotherapy prostate samples for DNA damage response proteins.
  
  
  RESULTS
  Between 2001 and 2004, 15 patients were entered on trial. Thirteen patients completed combined-modality treatment. Only one patient had signs of intra-operative inflammation. No patient had post-operative complication. There was no severe late gastrointestinal toxicity. Late genitourinary toxicity consisted of severe urinary incontinence in 2 of 13 patients. From a translational standpoint, irradiated prostate tumor tissues had long-term activation of the CDK-inhibitor p21(WAF) associated with reduced cell proliferation.
  
  
  CONCLUSIONS
  Intra-operative morbidity is low following short-course, pre-operative radiotherapy. A phase II trial is planned to fully document biochemical response with this combined-modality approach.
authors.affiliation: Princess Margaret Hospital (University Health Network), Toronto, Ont., Canada.
authors.forename: Stephane
authors.initials: S
authors.lastname: Supiot
authors.forename: Shubber
authors.initials: S
authors.lastname: Shubbar
authors.forename: Neil
authors.initials: N
authors.lastname: Fleshner
authors.forename: Padraig
authors.initials: P
authors.lastname: Warde
authors.forename: Karen
authors.initials: K
authors.lastname: Hersey
authors.forename: Kris
authors.initials: K
authors.lastname: Wallace
authors.forename: Heather
authors.initials: H
authors.lastname: Cole
authors.forename: Joan
authors.initials: J
authors.lastname: Sweet
authors.forename: John
authors.initials: J
authors.lastname: Tsihlias
authors.forename: Michael A S
authors.initials: MA
authors.lastname: Jewett
authors.forename: Laurence
authors.initials: L
authors.lastname: Klotz
authors.forename: Robert G
authors.initials: RG
authors.lastname: Bristow
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000368:Aged; D017209:Apoptosis; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods*; D016019:Survival Analysis; D016896:Treatment Outcome