title: Development and internal validation of a multivariable prediction model for biochemical failure after whole-gland salvage iodine-125 prostate brachytherapy for recurrent prostate cancer.
abstract: Localized recurrent prostate cancer after primary radiotherapy can be curatively treated using salvage iodine-125 ((125)I) brachytherapy. Selection is hampered by a lack of predictive factors for cancer control. This study aims to develop and internally validate a prognostic model for biochemical failure (BF) after salvage (125)I brachytherapy.
  
  
  
  Whole-gland salvage (125)I brachytherapy patients were treated between 1993 and 2010 in two radiotherapy centers in the Netherlands. Multivariable Cox regression was performed to assess the predictive value of clinical parameters related to BF (Phoenix-definition [prostate-specific antigen [PSA]-nadir + 2.0 ng/mL]). Missing data were handled by multiple imputation. The model's discriminatory ability was assessed with Harrell's C-statistic. Internal validation was performed using bootstrap resampling (2000 data sets). Goodness-of-fit was evaluated with calibration plots. All analyses were performed using the recently published TRIPOD (Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) statement.
  
  
  
  After median followup of 74 months (range 5-138), 43 of a total 62 patients developed BF. In multivariable analysis, disease-free survival interval (DFSI) after primary therapy and pre-salvage prostate-specific antigen doubling time (PSADT) were predictors of BF: corrected hazard ratio (HR) 0.99 (95% confidence interval 0.97-0.999; p = 0.04) and 0.94 (95% confidence interval 0.89-0.99; p = 0.03), both for a 1-month increase (optimism-adjusted C-statistic 0.70). Calibration was accurate up to 36 months. Of patients with PSADT >30 months and DFSI >60 months, 36-month biochemical disease-free survival was >75%. Every 12-month increase in DFSI will allow 3-month decrease in PSADT while maintaining the same biochemical recurrence-free rates.
  
  
  
  We have presented results from a cohort of patients undergoing salvage (125)I-brachytherapy. Our data show that better selection of patients is possible with the DFSI and PSADT.
authors.affiliation: Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: m.peters-10@umcutrecht.nl.
authors.forename: M
authors.initials: M
authors.lastname: Peters
authors.affiliation: Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: J R N
authors.initials: JRN
authors.lastname: van der Voort van Zyp
authors.affiliation: Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Moerland
authors.affiliation: Department of Radiation Oncology, Radiotherapeutic Institute RISO, Deventer, The Netherlands.
authors.forename: C J
authors.initials: CJ
authors.lastname: Hoekstra
authors.affiliation: Department of Radiation Oncology, Radiotherapeutic Institute RISO, Deventer, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: van de Pol
authors.affiliation: Department of Radiation Oncology, Radiotherapeutic Institute RISO, Deventer, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Westendorp
authors.affiliation: Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Maenhout
authors.affiliation: Department of Radiation Oncology, Radiotherapeutic Institute RISO, Deventer, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Kattevilder
authors.affiliation: Imaging Division, University Medical Center Utrecht, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: Verkooijen
authors.affiliation: Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Peter S N
authors.initials: PSN
authors.lastname: van Rossum
authors.affiliation: Division of Surgery and Interventional Science, University College London, UK; Department of Urology, University College London Hospitals, National Health Service (UCLH NHS) Foundation Trust, London, UK.
authors.forename: H U
authors.initials: HU
authors.lastname: Ahmed
authors.affiliation: Division of Surgery and Interventional Science, University College London, UK; Department of Urology, University College London Hospitals, National Health Service (UCLH NHS) Foundation Trust, London, UK; Department of Urology, Whittington Hospital NHS Trust, London, UK.
authors.forename: T T
authors.initials: TT
authors.lastname: Shah
authors.affiliation: Division of Surgery and Interventional Science, University College London, UK; Department of Urology, University College London Hospitals, National Health Service (UCLH NHS) Foundation Trust, London, UK; National Institute for Health Research (NIHR) University College London Hospitals (UCLH/UCL) Comprehensive Biomedical Research Centre, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Emberton
authors.affiliation: Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Vulpen
mesh_terms: D000368:Aged; D001918:Brachytherapy / Q000379:methods*; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000532:radiotherapy*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000532:radiotherapy*; D012189:Retrospective Studies; D016879:Salvage Therapy; D013997:Time Factors
chemical_list: D007457:Iodine Radioisotopes; D017430:Prostate-Specific Antigen
keywords: (125)I brachytherapy; Biochemical failure; Prediction model; Prostate cancer; Whole-gland salvage