TY - JOUR
T1 - 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
T2 - Presentation of risk scores for individual patient prognoses
AU - Peters, Max
AU - Kanthabalan, Abi
AU - Shah, Taimur T
AU - McCartan, Neil
AU - Moore, Caroline M.
AU - Arya, Manit
AU - van der Voort van Zyp, Jochem R.
AU - Moerland, Marinus A.
AU - Hindley, Richard G.
AU - Emberton, Mark
AU - Ahmed, Hashim U
N1 - Funding Information:
M. Emberton and H.U. Ahmed would like to acknowledge funding from the Medical Research Council (UK), the Pelican Cancer Foundation Charity, Prostate Cancer UK, St Peters Trust Charity, Prostate Cancer Research Center, the Wellcome Trust, National Institute of Health Research-Health Technology Assessment Program, National Institute of Health Research-i4i Program and the US National Institute of Health-National Cancer Institute. M. Emberton receives funding in part from the UK National Institute of Health Research UCLH/UCL Comprehensive Biomedical Research Center. M. Emberton and H.U. Ahmed previously received funding from GSK, Angiodynamics, and Advanced Medical Diagnostics for clinical trials. They currently receive trial funding from Trod Medical and Sophiris Inc. M. Emberton is a paid consultant to Steba Biotech and Sonacare. R.G. Hindley and M. Emberton have share options in Nuada Medical Ltd., UK. Ahmed and Emberton have previously received consultancy payments from Oncura/GE Healthcare and Steba Biotech. Both are paid consultants with Sophiris Inc. T.T. Shah would like to acknowledge funding from the St Peters Trust for clinical research and has received funding for conference attendance from Astellis, Ferring and Galil Medical.
Publisher Copyright:
© 2018
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Purpose Patient 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 methods A 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. Results Median 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. Conclusion Our model, once externally validated, could allow for better selection of patients for focal salvage HIFU.
AB - Purpose Patient 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 methods A 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. Results Median 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. Conclusion Our model, once externally validated, could allow for better selection of patients for focal salvage HIFU.
KW - Biochemical failure
KW - Composite endpoint
KW - Focal salvage high intensity focused ultrasound (HIFU)
KW - Prediction models
KW - Prostate cancer
UR - http://www.scopus.com/inward/record.url?scp=85029523208&partnerID=8YFLogxK
U2 - 10.1016/j.urolonc.2017.08.022
DO - 10.1016/j.urolonc.2017.08.022
M3 - Article
AN - SCOPUS:85029523208
SN - 1078-1439
VL - 36
SP - 13.e1-13.e10
JO - Urologic Oncology: Seminars and Original Investigations
JF - Urologic Oncology: Seminars and Original Investigations
IS - 1
ER -