title: The early toxicity of escalated versus standard dose conformal radiotherapy with neo-adjuvant androgen suppression for patients with localised prostate cancer: results from the MRC RT01 trial (ISRCTN47772397).
abstract: BACKGROUND
  Five-year disease-free survival rates for localised prostate cancer following standard doses of conventional radical external beam radiotherapy are around 80%. Conformal radiotherapy (CFRT) raises the possibility that radiotherapy doses can be increased and long-term efficacy outcomes improved, with safety an important consideration.
  
  
  METHODS
  MRC RT01 is a randomised controlled trial of 862 men with localised prostate cancer comparing Standard CFRT (64Gy/32f) versus Escalated CFRT (74Gy/37f), both administered with neo-adjuvant androgen suppression. Early toxicity was measured using physician-reported instruments (RTOG, LENT/SOM, Royal Marsden Scales) and patient-reported questionnaires (MOS SF-36, UCLA Prostate Cancer Index, FACT-P).
  
  
  RESULTS
  Overall early radiotherapy toxicity was similar, apart from increased bladder, bowel and sexual toxicity, in the Escalated Group during a short immediate post-radiotherapy period. Toxicity in both groups had abated by week 12. Using RTOG Acute Toxicity scores, cumulative Grade 2 bladder and bowel toxicity was 38% and 30% for Standard Group and 39% and 33% in Escalated Group, respectively. Urinary frequency (Royal Marsden Scale) improved in both groups from pre-androgen suppression to 6 months post-radiotherapy (p<0.001), but bowel and sexual functioning deteriorated. This pattern was supported by patient-completed assessments. Six months after starting radiotherapy the incidence of RTOG Grade > or = 2 side-effects was low (<1%); but there were six reports of rectal ulceration (6 Escalated Group), six haematuria (5 Escalated Group) and eight urethral stricture (6 Escalated Group).
  
  
  CONCLUSIONS
  The two CFRT schedules with neo-adjuvant androgen suppression have broadly similar early toxicity profiles except for the immediate post-RT period. At 6 months and compared to before hormone therapy, bladder symptoms improved, whereas bowel and sexual symptoms worsened. These assessments of early treatment safety will be complemented by further follow-up to document late side-effects and efficacy.
authors: Institute of Cancer Research and Royal Marsden Hospitals, Sutton, UK. david.dearnaley@icr.ac.uk
authors: David P
authors: DP
authors: Dearnaley
authors: Matthew R
authors: MR
authors: Sydes
authors: Ruth E
authors: RE
authors: Langley
authors: John D
authors: JD
authors: Graham
authors: Robert A
authors: RA
authors: Huddart
authors: Isabel
authors: I
authors: Syndikus
authors: John H L
authors: JH
authors: Matthews
authors: Christopher D
authors: CD
authors: Scrase
authors: Chakiath C
authors: CC
authors: Jose
authors: John
authors: J
authors: Logue
authors: Richard J
authors: RJ
authors: Stephens
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D012007:Rectum / Q000528:radiation effects; D001743:Urinary Bladder / Q000528:radiation effects
chemical_list: D000726:Androgen Antagonists; D007987:Gonadotropin-Releasing Hormone