Development and internal validation of prediction models for biochemical failure and composite failure after focal salvage high intensity focused ultrasound for local radiorecurrent prostate cancer: Presentation of risk scores for individual patient prognoses |
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| Authors: | Max Peters Abi Kanthabalan Taimur T. Shah Neil McCartan Caroline M. Moore Manit Arya Jochem R. van der Voort van Zyp Marinus A. Moerland Richard G. Hindley Mark Emberton Hashim U. Ahmed |
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| Affiliation: | 1. Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands;2. Division of Surgery and Interventional Science, University College London, London, UK;3. Department of Urology, UCLH NHS Foundation Trust, London, UK;4. Department of Urology, Whittington Hospital NHS Trust, London, UK;5. Department of Urology, Princess Alexandra Hospital NHS Trust, Harlow, UK;6. NIHR UCLH/UCL Comprehensive Biomedical Research Center, London, UK;7. Department of Urology, Basingstoke Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK;8. Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK;9. Imperial Urology, Imperial Healthcare NHS Trust, London, UK |
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| Abstract: | PurposePatient selection for focal salvage remains difficult. Therefore, we developed and internally validated prediction models for biochemical failure (BF) and a composite endpoint (CE) following focal salvage high intensity focused ultrasound (HIFU) for radiorecurrent prostate cancer.Materials and methodsA prospective HIFU registry identified 150 cases (November 2006–August 2015). Recurrence was assessed with multiparametric magnetic resonance imaging (MRI) combined with template prostate mapping biopsies, targeted biopsies, or systematic transrectal ultrasound-guided biopsies. Metastatic disease was ruled out with a positron emission tomography-computed tomography and a bone scan. Focal salvage HIFU consisted of quadrant-ablation, hemi-ablation, or index-lesion ablation. Cox-regression was used for BF (Phoenix-definition) and CE (BF/MRI+/biopsies+/local or systemic treatment/metastases+/prostate cancer specific mortality+). Internal validation was performed using bootstrap resampling (500 datasets) after which C-statistic and hazard ratios were adjusted. Models were calibrated and risk scores created.ResultsMedian follow-up was 35 months (interquartile range: 22–52). Median biochemical disease-free survival (DFS) was 33 months (95% CI: 23–45). Median CE-free survival was 24 months (95% CI: 21–35). After multivariable analysis, DFS interval after primary radiotherapy, presalvage prostate-specific antigen (PSA), PSA-doubling time, prostatic volume, and T-stage (both MRI based) predicted BF. For the CE, PSA-doubling time was not predictive but additionally, primary Gleason score was. The adjusted C-statistics were 0.68 and 0.64 for BF and CE, respectively. Calibration was accurate until 48 months. The risk scores showed 3 groups, with biochemical DFS of 60%, 35%, and 7% and CE-free survival of 40%, 24%, and 0% at 4 years.ConclusionOur model, once externally validated, could allow for better selection of patients for focal salvage HIFU. |
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| Keywords: | Focal salvage high intensity focused ultrasound (HIFU) Prostate cancer Prediction models Biochemical failure Composite endpoint |
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