title: Randomised pilot study of dose escalation using conformal radiotherapy in prostate cancer: long-term follow-up.
abstract: BACKGROUND
  Radical three-dimensional conformal radiotherapy (CFRT) with initial androgen suppression (AS) is a standard management for localised prostate cancer (PC). This pilot study evaluated the role of dose escalation and appropriate target volume margin. Here, we report long-term follow-up.
  
  
  METHODS
  Eligible patients had T1b-T3b N0 M0 PC. After neoadjuvant AS, they were randomised to CFRT, giving (a) 64 Gy with either a 1.0- or 1.5-cm margin and (b) ±10 Gy boost to the prostate alone.
  
  
  RESULTS
  One hundred and twenty-six men were randomised and treated. Median follow-up was 13.7 years. The median age was 66.6 years at randomisation. Median presenting prostate-specific antigen (PSA) was 14 ng ml(-1). Sixty-four out of 126 patients developed PSA failure. Forty-nine out of 126 patients restarted AS, 34 out of 126 developed metastases and 28 out of 126 developed castrate-resistant prostate cancer (CRPC). Fifty-one out of 126 patients died; 19 out of 51 died of PC. Median overall survival (OS) was 14.4 years. Although escalated dose results were favourable, no statistically significant differences were seen between the randomised groups; PSA control (hazard ratio (HR): 0.77 (95% confidence interval (CI): 0.47-1.26)), development of CRPC (HR: 0.81 (95% CI: 0.40-1.65)), PC-specific survival (HR: 0.59 (95% CI:0.23-1.49)) and OS (HR: 0.81 (95% CI: 0.47-1.40)). There was no evidence of a difference in PSA control according to margin size (HR: 1.01 (95% CI: 0.61-1.66)).
  
  
  CONCLUSIONS
  Long-term follow-up of this small pilot study is compatible with a benefit from dose escalation, but confirmation from larger trials is required. There was no obvious detriment using the smaller radiotherapy margin.
authors.affiliation: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton and London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Creak
authors.forename: E
authors.initials: E
authors.lastname: Hall
authors.forename: A
authors.initials: A
authors.lastname: Horwich
authors.forename: R
authors.initials: R
authors.lastname: Eeles
authors.forename: V
authors.initials: V
authors.lastname: Khoo
authors.forename: R
authors.initials: R
authors.lastname: Huddart
authors.forename: C
authors.initials: C
authors.lastname: Parker
authors.forename: C
authors.initials: C
authors.lastname: Griffin
authors.forename: M
authors.initials: M
authors.lastname: Bidmead
authors.forename: J
authors.initials: J
authors.lastname: Warrington
authors.forename: D
authors.initials: D
authors.lastname: Dearnaley
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D004307:Dose-Response Relationship, Radiation; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000473:pathology / Q000532:radiotherapy; D020266:Radiotherapy, Conformal / Q000379:methods
chemical_list: D000726:Androgen Antagonists