External validation of a risk model predicting failure of salvage focal ablation for prostate cancer

Alexander Light; Max Peters; Deepika Reddy; Abi Kanthabalan; Marjorie Otieno; Menelaos Pavlou; Rumana Omar; Sola Adeleke; Francesco Giganti; Chris Brew-Graves; Norman R Williams; Amr Emara; Athar Haroon; Arash Latifoltojar; Harbir Sidhu; Alex Freeman; Clement Orczyk; Ashok Nikapota; Tim Dudderidge; Richard G Hindley; Jaspal Virdi; Manit Arya; Heather Payne; Anita V Mitra; Jamshed Bomanji; Mathias Winkler; Gail Horan; Caroline Moore; Mark Emberton; Shonit Punwani; Hashim U Ahmed; Taimur T Shah

doi:10.1111/bju.16102

External validation of a risk model predicting failure of salvage focal ablation for prostate cancer

Alexander Light, Max Peters, Deepika Reddy, Abi Kanthabalan, Marjorie Otieno, Menelaos Pavlou, Rumana Omar, Sola Adeleke, Francesco Giganti, Chris Brew-Graves, Norman R Williams, Amr Emara, Athar Haroon, Arash Latifoltojar, Harbir Sidhu, Alex Freeman, Clement Orczyk, Ashok Nikapota, Tim Dudderidge, Richard G HindleyJaspal Virdi, Manit Arya, Heather Payne, Anita V Mitra, Jamshed Bomanji, Mathias Winkler, Gail Horan, Caroline Moore, Mark Emberton, Shonit Punwani, Hashim U Ahmed, Taimur T Shah^*

^*Corresponding author for this work

Department of Radiotherapy

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

OBJECTIVES: To externally validate a published model predicting failure within 2 years after salvage focal ablation in men with localised radiorecurrent prostate cancer using a prospective, UK multicentre dataset.

PATIENTS AND METHODS: Patients with biopsy-confirmed ≤T3bN0M0 cancer after previous external beam radiotherapy or brachytherapy were included from the FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial (NCT01883128; 2014-2018; six centres), and from the high-intensity focussed ultrasound (HIFU) Evaluation and Assessment of Treatment (HEAT) and International Cryotherapy Evaluation (ICE) UK-based registries (2006-2022; nine centres). Eligible patients underwent either salvage focal HIFU or cryotherapy, with the choice based predominantly on anatomical factors. Per the original multivariable Cox regression model, the predicted outcome was a composite failure outcome. Model performance was assessed at 2 years post-salvage with discrimination (concordance index [C-index]), calibration (calibration curve and slope), and decision curve analysis. For the latter, two clinically-reasonable risk threshold ranges of 0.14-0.52 and 0.26-0.36 were considered, corresponding to previously published pooled 2-year recurrence-free survival rates for salvage local treatments.

RESULTS: A total of 168 patients were included, of whom 84/168 (50%) experienced the primary outcome in all follow-ups, and 72/168 (43%) within 2 years. The C-index was 0.65 (95% confidence interval 0.58-0.71). On graphical inspection, there was close agreement between predicted and observed failure. The calibration slope was 1.01. In decision curve analysis, there was incremental net benefit vs a 'treat all' strategy at risk thresholds of ≥0.23. The net benefit was therefore higher across the majority of the 0.14-0.52 risk threshold range, and all of the 0.26-0.36 range.

CONCLUSION: In external validation using prospective, multicentre data, this model demonstrated modest discrimination but good calibration and clinical utility for predicting failure of salvage focal ablation within 2 years. This model could be reasonably used to improve selection of appropriate treatment candidates for salvage focal ablation, and its use should be considered when discussing salvage options with patients. Further validation in larger, international cohorts with longer follow-up is recommended.

Original language	English
Pages (from-to)	520-530
Number of pages	11
Journal	BJU International
Volume	132
Issue number	5
DOIs	https://doi.org/10.1111/bju.16102
Publication status	Published - Nov 2023

Keywords

ablation
cryotherapy
failure
focal therapy
high-intensity focussed ultrasound
prediction model
prostate cancer
radiotherapy
recurrence
salvage

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Light, A., Peters, M., Reddy, D., Kanthabalan, A., Otieno, M., Pavlou, M., Omar, R., Adeleke, S., Giganti, F., Brew-Graves, C., Williams, N. R., Emara, A., Haroon, A., Latifoltojar, A., Sidhu, H., Freeman, A., Orczyk, C., Nikapota, A., Dudderidge, T., ... Shah, T. T. (2023). External validation of a risk model predicting failure of salvage focal ablation for prostate cancer. BJU International, 132(5), 520-530. https://doi.org/10.1111/bju.16102

@article{f1a8be62ca794b64b2e7f8355e78e867,

title = "External validation of a risk model predicting failure of salvage focal ablation for prostate cancer",

abstract = "OBJECTIVES: To externally validate a published model predicting failure within 2 years after salvage focal ablation in men with localised radiorecurrent prostate cancer using a prospective, UK multicentre dataset.PATIENTS AND METHODS: Patients with biopsy-confirmed ≤T3bN0M0 cancer after previous external beam radiotherapy or brachytherapy were included from the FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial (NCT01883128; 2014-2018; six centres), and from the high-intensity focussed ultrasound (HIFU) Evaluation and Assessment of Treatment (HEAT) and International Cryotherapy Evaluation (ICE) UK-based registries (2006-2022; nine centres). Eligible patients underwent either salvage focal HIFU or cryotherapy, with the choice based predominantly on anatomical factors. Per the original multivariable Cox regression model, the predicted outcome was a composite failure outcome. Model performance was assessed at 2 years post-salvage with discrimination (concordance index [C-index]), calibration (calibration curve and slope), and decision curve analysis. For the latter, two clinically-reasonable risk threshold ranges of 0.14-0.52 and 0.26-0.36 were considered, corresponding to previously published pooled 2-year recurrence-free survival rates for salvage local treatments.RESULTS: A total of 168 patients were included, of whom 84/168 (50%) experienced the primary outcome in all follow-ups, and 72/168 (43%) within 2 years. The C-index was 0.65 (95% confidence interval 0.58-0.71). On graphical inspection, there was close agreement between predicted and observed failure. The calibration slope was 1.01. In decision curve analysis, there was incremental net benefit vs a 'treat all' strategy at risk thresholds of ≥0.23. The net benefit was therefore higher across the majority of the 0.14-0.52 risk threshold range, and all of the 0.26-0.36 range.CONCLUSION: In external validation using prospective, multicentre data, this model demonstrated modest discrimination but good calibration and clinical utility for predicting failure of salvage focal ablation within 2 years. This model could be reasonably used to improve selection of appropriate treatment candidates for salvage focal ablation, and its use should be considered when discussing salvage options with patients. Further validation in larger, international cohorts with longer follow-up is recommended.",

keywords = "ablation, cryotherapy, failure, focal therapy, high-intensity focussed ultrasound, prediction model, prostate cancer, radiotherapy, recurrence, salvage",

author = "Alexander Light and Max Peters and Deepika Reddy and Abi Kanthabalan and Marjorie Otieno and Menelaos Pavlou and Rumana Omar and Sola Adeleke and Francesco Giganti and Chris Brew-Graves and Williams, {Norman R} and Amr Emara and Athar Haroon and Arash Latifoltojar and Harbir Sidhu and Alex Freeman and Clement Orczyk and Ashok Nikapota and Tim Dudderidge and Hindley, {Richard G} and Jaspal Virdi and Manit Arya and Heather Payne and Mitra, {Anita V} and Jamshed Bomanji and Mathias Winkler and Gail Horan and Caroline Moore and Mark Emberton and Shonit Punwani and Ahmed, {Hashim U} and Shah, {Taimur T}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.",

year = "2023",

month = nov,

doi = "10.1111/bju.16102",

language = "English",

volume = "132",

pages = "520--530",

journal = "BJU International",

issn = "1464-4096",

publisher = "Wiley-Blackwell",

number = "5",

}

Light, A, Peters, M, Reddy, D, Kanthabalan, A, Otieno, M, Pavlou, M, Omar, R, Adeleke, S, Giganti, F, Brew-Graves, C, Williams, NR, Emara, A, Haroon, A, Latifoltojar, A, Sidhu, H, Freeman, A, Orczyk, C, Nikapota, A, Dudderidge, T, Hindley, RG, Virdi, J, Arya, M, Payne, H, Mitra, AV, Bomanji, J, Winkler, M, Horan, G, Moore, C, Emberton, M, Punwani, S, Ahmed, HU & Shah, TT 2023, 'External validation of a risk model predicting failure of salvage focal ablation for prostate cancer', BJU International, vol. 132, no. 5, pp. 520-530. https://doi.org/10.1111/bju.16102

TY - JOUR

T1 - External validation of a risk model predicting failure of salvage focal ablation for prostate cancer

AU - Light, Alexander

AU - Peters, Max

AU - Reddy, Deepika

AU - Kanthabalan, Abi

AU - Otieno, Marjorie

AU - Pavlou, Menelaos

AU - Omar, Rumana

AU - Adeleke, Sola

AU - Giganti, Francesco

AU - Brew-Graves, Chris

AU - Williams, Norman R

AU - Emara, Amr

AU - Haroon, Athar

AU - Latifoltojar, Arash

AU - Sidhu, Harbir

AU - Freeman, Alex

AU - Orczyk, Clement

AU - Nikapota, Ashok

AU - Dudderidge, Tim

AU - Hindley, Richard G

AU - Virdi, Jaspal

AU - Arya, Manit

AU - Payne, Heather

AU - Mitra, Anita V

AU - Bomanji, Jamshed

AU - Winkler, Mathias

AU - Horan, Gail

AU - Moore, Caroline

AU - Emberton, Mark

AU - Punwani, Shonit

AU - Ahmed, Hashim U

AU - Shah, Taimur T

PY - 2023/11

Y1 - 2023/11

N2 - OBJECTIVES: To externally validate a published model predicting failure within 2 years after salvage focal ablation in men with localised radiorecurrent prostate cancer using a prospective, UK multicentre dataset.PATIENTS AND METHODS: Patients with biopsy-confirmed ≤T3bN0M0 cancer after previous external beam radiotherapy or brachytherapy were included from the FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial (NCT01883128; 2014-2018; six centres), and from the high-intensity focussed ultrasound (HIFU) Evaluation and Assessment of Treatment (HEAT) and International Cryotherapy Evaluation (ICE) UK-based registries (2006-2022; nine centres). Eligible patients underwent either salvage focal HIFU or cryotherapy, with the choice based predominantly on anatomical factors. Per the original multivariable Cox regression model, the predicted outcome was a composite failure outcome. Model performance was assessed at 2 years post-salvage with discrimination (concordance index [C-index]), calibration (calibration curve and slope), and decision curve analysis. For the latter, two clinically-reasonable risk threshold ranges of 0.14-0.52 and 0.26-0.36 were considered, corresponding to previously published pooled 2-year recurrence-free survival rates for salvage local treatments.RESULTS: A total of 168 patients were included, of whom 84/168 (50%) experienced the primary outcome in all follow-ups, and 72/168 (43%) within 2 years. The C-index was 0.65 (95% confidence interval 0.58-0.71). On graphical inspection, there was close agreement between predicted and observed failure. The calibration slope was 1.01. In decision curve analysis, there was incremental net benefit vs a 'treat all' strategy at risk thresholds of ≥0.23. The net benefit was therefore higher across the majority of the 0.14-0.52 risk threshold range, and all of the 0.26-0.36 range.CONCLUSION: In external validation using prospective, multicentre data, this model demonstrated modest discrimination but good calibration and clinical utility for predicting failure of salvage focal ablation within 2 years. This model could be reasonably used to improve selection of appropriate treatment candidates for salvage focal ablation, and its use should be considered when discussing salvage options with patients. Further validation in larger, international cohorts with longer follow-up is recommended.

AB - OBJECTIVES: To externally validate a published model predicting failure within 2 years after salvage focal ablation in men with localised radiorecurrent prostate cancer using a prospective, UK multicentre dataset.PATIENTS AND METHODS: Patients with biopsy-confirmed ≤T3bN0M0 cancer after previous external beam radiotherapy or brachytherapy were included from the FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial (NCT01883128; 2014-2018; six centres), and from the high-intensity focussed ultrasound (HIFU) Evaluation and Assessment of Treatment (HEAT) and International Cryotherapy Evaluation (ICE) UK-based registries (2006-2022; nine centres). Eligible patients underwent either salvage focal HIFU or cryotherapy, with the choice based predominantly on anatomical factors. Per the original multivariable Cox regression model, the predicted outcome was a composite failure outcome. Model performance was assessed at 2 years post-salvage with discrimination (concordance index [C-index]), calibration (calibration curve and slope), and decision curve analysis. For the latter, two clinically-reasonable risk threshold ranges of 0.14-0.52 and 0.26-0.36 were considered, corresponding to previously published pooled 2-year recurrence-free survival rates for salvage local treatments.RESULTS: A total of 168 patients were included, of whom 84/168 (50%) experienced the primary outcome in all follow-ups, and 72/168 (43%) within 2 years. The C-index was 0.65 (95% confidence interval 0.58-0.71). On graphical inspection, there was close agreement between predicted and observed failure. The calibration slope was 1.01. In decision curve analysis, there was incremental net benefit vs a 'treat all' strategy at risk thresholds of ≥0.23. The net benefit was therefore higher across the majority of the 0.14-0.52 risk threshold range, and all of the 0.26-0.36 range.CONCLUSION: In external validation using prospective, multicentre data, this model demonstrated modest discrimination but good calibration and clinical utility for predicting failure of salvage focal ablation within 2 years. This model could be reasonably used to improve selection of appropriate treatment candidates for salvage focal ablation, and its use should be considered when discussing salvage options with patients. Further validation in larger, international cohorts with longer follow-up is recommended.

KW - ablation

KW - cryotherapy

KW - failure

KW - focal therapy

KW - high-intensity focussed ultrasound

KW - prediction model

KW - prostate cancer

KW - radiotherapy

KW - recurrence

KW - salvage

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U2 - 10.1111/bju.16102

DO - 10.1111/bju.16102

M3 - Article

C2 - 37385981

SN - 1464-4096

VL - 132

SP - 520

EP - 530

JO - BJU International

JF - BJU International

IS - 5

ER -

External validation of a risk model predicting failure of salvage focal ablation for prostate cancer

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