title: Urinary symptoms following external beam radiotherapy of the prostate: Dose-symptom correlates with multiple-event and event-count models.
abstract: OBJECTIVE
  This study aimed to compare urinary dose-symptom correlates after external beam radiotherapy of the prostate using commonly utilised peak-symptom models to multiple-event and event-count models which account for repeated events.
  
  
  METHODS
  Urinary symptoms (dysuria, haematuria, incontinence and frequency) from 754 participants from TROG 03.04-RADAR trial were analysed. Relative (R1-R75 Gy) and absolute (A60-A75Gy) bladder dose-surface area receiving more than a threshold dose and equivalent uniform dose using exponent a (range: a ∈[1 … 100]) were derived. The dose-symptom correlates were analysed using; peak-symptom (logistic), multiple-event (generalised estimating equation) and event-count (negative binomial regression) models.
  
  
  RESULTS
  Stronger dose-symptom correlates were found for incontinence and frequency using multiple-event and/or event-count models. For dysuria and haematuria, similar or better relationships were found using peak-symptom models. Dysuria, haematuria and high grade (⩾ 2) incontinence were associated to high dose (R61-R71 Gy). Frequency and low grade (⩾ 1) incontinence were associated to low and intermediate dose-surface parameters (R13-R41Gy). Frequency showed a parallel behaviour (a=1) while dysuria, haematuria and incontinence showed a more serial behaviour (a=4 to a ⩾ 100). Relative dose-surface showed stronger dose-symptom associations.
  
  
  CONCLUSIONS
  For certain endpoints, the multiple-event and event-count models provide stronger correlates over peak-symptom models. Accounting for multiple events may be advantageous for a more complete understanding of urinary dose-symptom relationships.
authors.affiliation: School of Physics, University of Western Australia, Australia; School of Health Sciences, National University of Malaysia, Malaysia. Electronic address: noorazrul.yahya@research.uwa.edu.au.
authors.forename: Noorazrul
authors.initials: N
authors.lastname: Yahya
authors.affiliation: School of Physics, University of Western Australia, Australia; Department of Radiation Oncology, Sir Charles Gairdner Hospital, Australia.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Ebert
authors.affiliation: Institute for Health Research, University of Notre Dame, Fremantle, Australia.
authors.forename: Max
authors.initials: M
authors.lastname: Bulsara
authors.affiliation: School of Physics, University of Western Australia, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: House
authors.affiliation: Department of Radiation Oncology, Sir Charles Gairdner Hospital, Australia.
authors.forename: Angel
authors.initials: A
authors.lastname: Kennedy
authors.affiliation: Department of Radiation Oncology, Sir Charles Gairdner Hospital, Australia; School of Surgery, University of Western Australia, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Joseph
authors.affiliation: School of Medicine and Public Health, University of Newcastle, Australia.
authors.forename: James W
authors.initials: JW
authors.lastname: Denham
mesh_terms: D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011878:Radiotherapy / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D001743:Urinary Bladder / Q000528:radiation effects; D014549:Urinary Incontinence / Q000209:etiology*
keywords: Event-count model; Multiple-event model; Normal tissue complications; Prostate radiotherapy; Urinary symptoms