Development and internal validation of a multivariable prediction model for biochemical failure after whole-gland salvage iodine-125 prostate brachytherapy for recurrent prostate cancer

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.

Brachytherapy. 2016 Feb 29 [Epub ahead of print]

M Peters, J R N van der Voort van Zyp, M A Moerland, C J Hoekstra, S van de Pol, H Westendorp, M Maenhout, R Kattevilder, H M Verkooijen, P S N van Rossum, H U Ahmed, T T Shah, M Emberton, M van Vulpen

Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: ., Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands., Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands., Department of Radiation Oncology, Radiotherapeutic Institute RISO, Deventer, The Netherlands., Department of Radiation Oncology, Radiotherapeutic Institute RISO, Deventer, The Netherlands., Department of Radiation Oncology, Radiotherapeutic Institute RISO, Deventer, The Netherlands., Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands., Department of Radiation Oncology, Radiotherapeutic Institute RISO, Deventer, The Netherlands., Imaging Division, University Medical Center Utrecht, The Netherlands., Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands., 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., 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., 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., Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.

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