title: Multivariable model development and internal validation for prostate cancer specific survival and overall survival after whole-gland salvage Iodine-125 prostate brachytherapy.
abstract: Whole-gland salvage Iodine-125-brachytherapy is a potentially curative treatment strategy for localised prostate cancer (PCa) recurrences after radiotherapy. Prognostic factors influencing PCa-specific and overall survival (PCaSS & OS) are not known. The objective of this study was to develop a multivariable, internally validated prognostic model for survival after whole-gland salvage I-125-brachytherapy.
  
  
  
  Whole-gland salvage I-125-brachytherapy patients treated in the Netherlands from 1993-2010 were included. Eligible patients had a transrectal ultrasound-guided biopsy-confirmed localised recurrence after biochemical failure (clinical judgement, ASTRO or Phoenix-definition). Recurrences were assessed clinically and with CT and/or MRI. Metastases were excluded using CT/MRI and technetium-99m scintigraphy. Multivariable Cox-regression was used to assess the predictive value of clinical characteristics in relation to PCa-specific and overall mortality. PCa-specific mortality was defined as patients dying with distant metastases present. Missing data were handled using multiple imputation (20 imputed sets). Internal validation was performed and the C-statistic calculated. Calibration plots were created to visually assess the goodness-of-fit of the final model. Optimism-corrected survival proportions were calculated. All analyses were performed according to the TRIPOD statement.
  
  
  
  Median total follow-up was 78months (range 5-139). A total of 62 patients were treated, of which 28 (45%) died from PCa after mean (±SD) 82 (±36) months. Overall, 36 patients (58%) patients died after mean 84 (±40) months. PSA doubling time (PSADT) remained a predictive factor for both types of mortality (PCa-specific and overall): corrected hazard ratio's (HR's) 0.92 (95% CI: 0.86-0.98, p=0.02) and 0.94 (95% CI: 0.90-0.99, p=0.01), respectively (C-statistics 0.71 and 0.69, respectively). Calibration was accurate up to 96month follow-up. Over 80% of patients can survive 8years if PSADT>24months (PCaSS) and >33months (OS). Only approximately 50% survival is achieved with a PSADT of 12months.
  
  
  
  A PSADT of respectively >24months and >33months can result in >80% probability of PCa- specific and overall survival 8years after whole-gland salvage I-125-brachytherapy. Survival should be weighed against toxicity from a salvage procedure. Larger series and external validation are necessary.
authors.affiliation: Department of Radiation Oncology, University Medical Centre Utrecht, The Netherlands. Electronic address: m.peters-10@umcutrecht.nl.
authors.forename: Max
authors.initials: M
authors.lastname: Peters
authors.affiliation: Department of Radiation Oncology, University Medical Centre Utrecht, The Netherlands.
authors.forename: Jochem R N
authors.initials: JR
authors.lastname: van der Voort van Zyp
authors.affiliation: Department of Radiation Oncology, University Medical Centre Utrecht, The Netherlands.
authors.forename: Marinus A
authors.initials: MA
authors.lastname: Moerland
authors.affiliation: Radiotherapeutic Institute RISO, Deventer, The Netherlands.
authors.forename: Carel J
authors.initials: CJ
authors.lastname: Hoekstra
authors.affiliation: Radiotherapeutic Institute RISO, Deventer, The Netherlands.
authors.forename: Sandrine
authors.initials: S
authors.lastname: van de Pol
authors.affiliation: Radiotherapeutic Institute RISO, Deventer, The Netherlands.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Westendorp
authors.affiliation: Department of Radiation Oncology, University Medical Centre Utrecht, The Netherlands.
authors.forename: Metha
authors.initials: M
authors.lastname: Maenhout
authors.affiliation: Radiotherapeutic Institute RISO, Deventer, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Kattevilder
authors.affiliation: Imaging Division, University Medical Centre Utrecht, The Netherlands.
authors.forename: Helena M
authors.initials: HM
authors.lastname: Verkooijen
authors.affiliation: Department of Radiation Oncology, University Medical Centre Utrecht, The Netherlands.
authors.forename: Peter S N
authors.initials: PS
authors.lastname: van Rossum
authors.affiliation: Division of Surgery and Interventional Science, University College London, UK; Department of Urology, UCLH NHS Foundation Trust, UK.
authors.forename: Hashim U
authors.initials: HU
authors.lastname: Ahmed
authors.affiliation: Division of Surgery and Interventional Science, University College London, UK; Department of Urology, UCLH NHS Foundation Trust, UK; Department of Urology, Whittington Hospital NHS Trust, London, UK.
authors.forename: Taimur T
authors.initials: TT
authors.lastname: Shah
authors.affiliation: Division of Surgery and Interventional Science, University College London, UK; Department of Urology, UCLH NHS Foundation Trust, UK; NIHR UCLH/UCL Comprehensive Biomedical Research Centre, London, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Emberton
authors.affiliation: Department of Radiation Oncology, University Medical Centre Utrecht, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: van Vulpen
mesh_terms: D000368:Aged; D001918:Brachytherapy / Q000379:methods*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D016879:Salvage Therapy / Q000379:methods
chemical_list: D007457:Iodine Radioisotopes
keywords: I-125-brachytherapy; Predictive factors; Prostate cancer; Survival; Whole-gland salvage