title: Acute and Late Adverse Events Associated With Radical Radiation Therapy Prostate Cancer Treatment: A Systematic Review of Clinician and Patient Toxicity Reporting in Randomized Controlled Trials.
abstract: This review aimed to determine the clinician and patient reported outcome (PRO) instruments currently usedin randomized controlled trials (RCTs) of radical radiation therapy for nonmetastatic prostate cancer to report acute and late adverse events (AEs), review the quality of methodology and PRO reporting, and report the prevalence of acute and late AEs.
  
  
  
  The MEDLINE, EMBASE, and Cochrane databases were searched between April and August 2014 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Identified reports were reviewed according to the PRO Consolidated Standards of Reporting Trials (CONSORT) guidelines and the Cochrane Risk of Bias tool. In all, 1149 records were screened, and 21 articles were included in the final review.
  
  
  
  We determined the acute and late AEs for 9040 patients enrolled in 15 different RCTs. Only clinician reported instruments were used to report acute AEs <3 months (eg, Radiation Therapy Oncology Group [RTOG] and Common Terminology Criteria for Adverse Events [CTCAE]). For late clinician reporting, the Late Effects on Normal Tissues-Subjective, Objective, Management and Analytic scale and RTOG were used and were often augmented with additional items to provide comprehensive coverage of sexual functioning and anorectal symptoms. Some late AEs were reported (48% articles) using PROs (eg, ULCA-PCI [University of California, Los Angeles Prostate Cancer Index], FACT-G and P [Functional Assessment of Cancer Therapy General & Prostate Module], EORTC QLQC-30 + PR25 [European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire & Prostate Module]); however, a definitive "preferred" instrument was not evident.
  
  
  
  Our findings are at odds with recent movements toward including patient voices in reporting of AEs and patient engagement in clinical research. We recommend including PRO to evaluate radical radiation therapy before, during, and after the treatment to fully capture patient experiences, and we support the development of predictive models for late effects based on the severity of early toxicity.
  
  
  
  Patient reporting of acute and late AEs is underrepresented in radiation therapy trials. We recommend working toward a consistent approach to PRO assessment of radiation therapy-related AEs.
authors.affiliation: Psychology Group, School of Social Sciences, Leeds Beckett University, Leeds, UK; Patient Reported Outcomes Group, Leeds Institute of Cancer Studies and Pathology, University of Leeds, St James's Hospital, Leeds, UK. Electronic address: T.Holch@Leedsbeckett.ac.uk.
authors.forename: Patricia
authors.initials: P
authors.lastname: Holch
authors.affiliation: Patient Reported Outcomes Group, Leeds Institute of Cancer Studies and Pathology, University of Leeds, St James's Hospital, Leeds, UK; Leeds Teaching Hospitals NHS Trust, St James's Institute of Oncology, St James's Hospital, Leeds, UK.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Henry
authors.affiliation: The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Davidson
authors.affiliation: Patient Reported Outcomes Group, Leeds Institute of Cancer Studies and Pathology, University of Leeds, St James's Hospital, Leeds, UK.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gilbert
authors.affiliation: The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Routledge
authors.affiliation: Patient Reported Outcomes Group, Leeds Institute of Cancer Studies and Pathology, University of Leeds, St James's Hospital, Leeds, UK.
authors.forename: Leanne
authors.initials: L
authors.lastname: Shearsmith
authors.affiliation: Leeds Teaching Hospitals NHS Trust, St James's Institute of Oncology, St James's Hospital, Leeds, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Franks
authors.affiliation: Patient Reported Outcomes Group, Leeds Institute of Cancer Studies and Pathology, University of Leeds, St James's Hospital, Leeds, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Ingleson
authors.affiliation: Patient Reported Outcomes Group, Leeds Institute of Cancer Studies and Pathology, University of Leeds, St James's Hospital, Leeds, UK.
authors.forename: Abigail
authors.initials: A
authors.lastname: Albutt
authors.affiliation: Patient Reported Outcomes Group, Leeds Institute of Cancer Studies and Pathology, University of Leeds, St James's Hospital, Leeds, UK.
authors.forename: Galina
authors.initials: G
authors.lastname: Velikova
mesh_terms: D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care / Q000379:methods; D063868:Patient Outcome Assessment; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011788:Quality of Life; D018787:Radiation Oncology; D011878:Radiotherapy / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome