title: Image guided dose escalated prostate radiotherapy: still room to improve.
abstract: BACKGROUND
  Prostate radiotherapy (RT) dose escalation has been reported to result in improved biochemical control at the cost of greater late toxicity. We report on the application of 79.8 Gy in 42 fractions of prostate image guided RT (IGRT). The primary objective was to assess 5-year biochemical control and potential prognostic factors by the Phoenix definition. Secondary endpoints included acute and late toxicity by the Radiotherapy Oncology Group (RTOG) scoring scales.
  
  
  METHODS
  From October/2001 and June/2003, 259 men were treated with at least 2-years follow-up. 59 patients had low, 163 intermediate and 37 high risk disease. 43 had adjuvant hormonal therapy (HT), mostly for high- or multiple risk factor intermediate-risk disease (n = 25). They received either 3-dimensional conformal RT (3DCRT, n = 226) or intensity modulated RT (IMRT) including daily on-line IGRT with intraprostatic fiducial markers.
  
  
  RESULTS
  Median follow-up was 67.8 months (range 24.4-84.7). There was no severe (grade 3-4) acute toxicity, and grade 2 acute gastrointestinal (GI) toxicity was unusual (10.1%). The 5-year incidence of grade 2-3 late GI and genitourinary (GU) toxicity was 13.7% and 12.1%, with corresponding grade 3 figures of 3.5% and 2.0% respectively. HT had an association with an increased risk of grade 2-3 late GI toxicity (11% v 21%, p = 0.018). Using the Phoenix definition for biochemical failure, the 5 year-bNED is 88.4%, 76.5% and 77.9% for low, intermediate and high risk patients respectively. On univariate analysis, T-category and Gleason grade correlated with Phoenix bNED (p = 0.006 and 0.039 respectively). Hormonal therapy was not a significant prognostic factor on uni- or multi-variate analysis. Men with positive prostate biopsies following RT had a lower chance of bNED at 5 years (34.4% v 64.3%; p = 0.147).
  
  
  CONCLUSIONS
  IGRT to 79.8 Gy results in favourable rates of late toxicity compared with published non-IGRT treated cohorts. Future avenues of investigation for toxicity reduction include IMRT, margin reduction, and dose modulation targeted to sites of disease burden. Further work is required to maximize efficacy beyond that achieved through radiation dose escalation alone.
authors.affiliation: Princess Margaret Hospital, Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada. jarad.martin@roq.net.au
authors.forename: Jarad M
authors.initials: JM
authors.lastname: Martin
authors.forename: Andrew
authors.initials: A
authors.lastname: Bayley
authors.forename: Robert
authors.initials: R
authors.lastname: Bristow
authors.forename: Peter
authors.initials: P
authors.lastname: Chung
authors.forename: Mary
authors.initials: M
authors.lastname: Gospodarowicz
authors.forename: Cynthia
authors.initials: C
authors.lastname: Menard
authors.forename: Michael
authors.initials: M
authors.lastname: Milosevic
authors.forename: Tara
authors.initials: T
authors.lastname: Rosewall
authors.forename: Padraig R
authors.initials: PR
authors.lastname: Warde
authors.forename: Charles N
authors.initials: CN
authors.lastname: Catton
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy*; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003952:Diagnostic Imaging; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal