title: A novel method for predicting late genitourinary toxicity after prostate radiation therapy and the need for age-based risk-adapted dose constraints.
abstract: BACKGROUND
  There are no well-established normal tissue sparing dose-volume histogram (DVH) criteria that limit the risk of urinary toxicity from prostate radiation therapy (RT). The aim of this study was to determine which criteria predict late toxicity among various DVH parameters when contouring the entire solid bladder and its contents versus the bladder wall. The area under the histogram curve (AUHC) was also analyzed.
  
  
  METHODS
  From 1993 to 2000, 503 men with prostate cancer received 3-dimensional conformal RT (median follow-up time, 71 months). The whole bladder and the bladder wall were contoured in all patients. The primary endpoint was grade ≥2 genitourinary (GU) toxicity occurring ≥3 months after completion of RT. Cox regressions of time to grade ≥2 toxicity were estimated separately for the entire bladder and bladder wall. Concordance probability estimates (CPE) assessed model discriminative ability. Before training the models, an external random test group of 100 men was set aside for testing. Separate analyses were performed based on the mean age (≤ 68 vs >68 years).
  
  
  RESULTS
  Age, pretreatment urinary symptoms, mean dose (entire bladder and bladder wall), and AUHC (entire bladder and bladder wall) were significant (P<.05) in multivariable analysis. Overall, bladder wall CPE values were higher than solid bladder values. The AUHC for bladder wall provided the greatest discrimination for late bladder toxicity when compared with alternative DVH points, with CPE values of 0.68 for age ≤68 years and 0.81 for age >68 years.
  
  
  CONCLUSIONS
  The AUHC method based on bladder wall volumes was superior for predicting late GU toxicity. Age >68 years was associated with late grade ≥2 GU toxicity, which suggests that risk-adapted dose constraints based on age should be explored.
authors.affiliation: Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Awad A
authors.initials: AA
authors.lastname: Ahmed
authors.forename: Brian
authors.initials: B
authors.lastname: Egleston
authors.forename: Pino
authors.initials: P
authors.lastname: Alcantara
authors.forename: Linna
authors.initials: L
authors.lastname: Li
authors.forename: Alan
authors.initials: A
authors.lastname: Pollack
authors.forename: Eric M
authors.initials: EM
authors.lastname: Horwitz
authors.forename: Mark K
authors.initials: MK
authors.lastname: Buyyounouski
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000532:radiotherapy*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D058958:Organs at Risk / Q000000981:diagnostic imaging / Q000528:radiation effects*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000473:pathology*; D011859:Radiography; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal; D001743:Urinary Bladder / Q000000981:diagnostic imaging / Q000528:radiation effects*