title: Urinary bladder dose-response relationships for patient-reported genitourinary morbidity domains following prostate cancer radiotherapy.
abstract: Radiotherapy (RT) induced genitourinary (GU) morbidity is typically assessed by physicians as single symptoms or aggregated scores including symptoms from various domains. Here we apply a method to group patient-reported GU symptoms after RT for localized prostate cancer based on their interplay, and study how these relate to urinary bladder dose.
  
  
  
  Data were taken from two Scandinavian studies (N=207/276) including men treated with external-beam RT (EBRT) to 78/70Gy (2Gy/fraction; median time-to-follow-up: 3.6-6.4y). Within and across cohorts, bladder dose-volume parameters were tested as predictors for GU symptom domains identified from two study-specific questionnaires (35 questions on frequency, incontinence, obstruction, pain, urgency, and sensory symptoms) using univariate and multivariate logistic regression analysis (MVA) with 10-fold cross-validation. Performance was evaluated using Area Under the Receiver Operating Characteristic Curve (Az).
  
  
  
  For the identified Incontinence (2-5 symptoms), Obstruction (3-5 symptoms), and Urgency (2-7 symptoms) domains, MVA demonstrated that bladder doses close to the prescription doses were the strongest predictors for Obstruction (Az: 0.53-0.57) and Urgency (Az: 0.60). For Obstruction, performance increased for the across cohort analysis (Az: 0.61-0.64).
  
  
  
  Our identified patient-reported GU symptom domains suggest that high urinary bladder doses, and increased focus on both obstruction and urgency is likely to further add to the understanding of GU tract RT responses.
authors.affiliation: Dept of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, USA. Electronic address: thorm@mskcc.org.
authors.forename: Maria
authors.initials: M
authors.lastname: Thor
authors.affiliation: Radiation Physics, University of Gothenburg, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Olsson
authors.affiliation: Dept of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Jung Hun
authors.initials: JH
authors.lastname: Oh
authors.affiliation: Depts of Medical Physics of Oncology, Aarhus University Hospital, Denmark.
authors.forename: Stine Elleberg
authors.initials: SE
authors.lastname: Petersen
authors.affiliation: Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Alsadius
authors.affiliation: Depts of Medical Physics of Oncology, Aarhus University Hospital, Denmark.
authors.forename: Lise
authors.initials: L
authors.lastname: Bentzen
authors.affiliation: Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Niclas
authors.initials: N
authors.lastname: Pettersson
authors.affiliation: Depts of Medical Physics of Oncology, Aarhus University Hospital, Denmark.
authors.forename: Ludvig Paul
authors.initials: LP
authors.lastname: Muren
authors.affiliation: Depts of Medical Physics of Oncology, Aarhus University Hospital, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Høyer
authors.affiliation: Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Steineck
authors.affiliation: Dept of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Deasy
mesh_terms: D000368:Aged; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D001743:Urinary Bladder / Q000528:radiation effects*; D014549:Urinary Incontinence / Q000209:etiology
keywords: Bladder; Dose–response; Patient-reported outcome; Prostate cancer; Radiotherapy; Toxicity